1,106
Views
45
CrossRef citations to date
0
Altmetric
Reviews

Pharmacological potential of methylxanthines: Retrospective analysis and future expectations

, ORCID Icon, &

References

  • 2014. Planning Committee for a Workshop on Potential Health Hazards Associated with Consumption of Caffeine in Food and Dietary Supplements; Food and Nutrition Board; Board on Health Sciences Policy; Institute of Medicine. Caffeine in Food and Dietary Supplements: Examining Safety: Workshop Summary. Washington, DC: The National Academies Press. https://doi.org/10.17226/18607.
  • Abu Jawdeh, E. G., M. O'Riordan, A. Limrungsikul, A. Bandyopadhyay, B. M. Argus, P. E. Nakad, S. Supapannachart, K. A. Yunis, P. G. Davis, and R. J. Martin. 2013. Methylxanthine use for apnea of prematurity among an international cohort of neonatologists. Journal of Neonatal-Perinatal Medicine 6:251–56.
  • Acheson, K. J., G. Gremaud, I. Meirim, F. Montigon, Y. Krebs, L. B. Fay, L.-J. Gay, P. Schneiter, C. Schindler, and L. Tappy. 2004. Metabolic effects of caffeine in humans: lipid oxidation or futile cycling? The American Journal of Clinical Nutrition 79:40–46. doi:10.1093/ajcn/79.1.40.
  • Adams, R. F., F. L. Vandemark, and G. J. Schmidt. 1976. More sensitive high-pressure liquid-chromatographic determiantion of theophylline in serum. Clinical Chemistry 22:1903–1906.
  • Ådén, U. 2011. Methylxanthines during pregnancy and early postnatal life. In Methylxanthines, 373–89. Berlin: Springer Berlin Heidelberg.
  • Airavaara, M., M. H. Voutilainen, Y. Wang, and B. Hoffer. 2012. Neurorestoration. Parkinsonism & related disorders 18:S143–46. doi:10.1016/S1353-8020(11)70045-1.
  • Alsene, K., J. Deckert, P. Sand, and H. de Wit. 2003. Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology 28:1694–702. doi:10.1038/sj.npp.1300232.
  • Alves, M. G., A. D. Martins, N. F. Teixeira, L. Rato, P. F. Oliveira, and B. M. Silva. 2015. White tea consumption improves cardiac glycolytic and oxidative profile of prediabetic rats. Journal of Functional Foods 14:102–10. doi:10.1016/j.jff.2015.01.019.
  • Angelucci, M. E. M., C. Cesário, R. H. Hiroi, P. L. Rosalen, and C. D. Cunha. 2002. Effects of caffeine on learning and memory in rats tested in the Morris water maze. Brazilian Journal of Medical and Biological Research 35:1201–8. doi:10.1590/S0100-879X2002001000013.
  • Anselme, F., K. Collomp, B. Mercier, S. Ahmaïdi, and C. Prefaut. 1992. Caffeine increases maximal anaerobic power and blood lactate concentration. European Journal of Applied Physiology and Occupational Physiology 65:188–91. doi:10.1007/BF00705079.
  • Arab, L., M. L. Biggs, E. S. O'Meara, W. T. Longstreth, P. K. Crane, and A. L. Fitzpatrick. 2011. Gender differences in tea, coffee, and cognitive decline in the elderly: the cardiovascular health study. Journal of Alzheimer's disease: JAD 27:553–66.
  • Aranda, J. V., K. Beharry, G. B. Valencia, G. Natarajan, and J. Davis. 2010. Caffeine impact on neonatal morbidities. The Journal of Maternal-Fetal & Neonatal Medicine 23:20–23. doi:10.3109/14767058.2010.517704.
  • Aranda, J. V., W. Gorman, H. Bergsteinsson, and T. Gunn. 1977. Efficacy of caffeine in treatment of apnea in the low-birth-weight infant. The Journal of Pediatrics 90:467–72. doi:10.1016/S0022-3476(77)80718-X.
  • Aranda, J. V., T. Turmen, and B. I. Sasyniuk. 1980. Pharmacokinetics of diuretics and methylxanthines in the neonate. European Journal of Clinical Pharmacology 18:55–63. doi:10.1007/BF00561479.
  • Arendash, G. W., and C. Cao. 2010. Caffeine and coffee as therapeutics against Alzheimer's disease. Journal of Alzheimers Disease: JAD 20:S117–26. doi:10.3233/JAD-2010-091249.
  • Arendash, G. W., T. Mori, C. Cao, M. Mamcarz, M. Runfeldt, A. Dickson, K. Rezai-Zadeh, J. Tane, B. A. Citron, X. Lin, V. Echeverria, and H. Potter. 2009. Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice. Journal of Alzheimers Disease: JAD 17:661–80. doi:10.3233/JAD-2009-1087.
  • Arendash, G. W., W. Schleif, K. Rezai-Zadeh, E. K. Jackson, L. C. Zacharia, J. R. Cracchiolo, D. Shippy, and J. Tan. 2006. Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain β-amyloid production. Neuroscience 142:941–52. doi:10.1016/j.neuroscience.2006.07.021.
  • Arnaud, M. J. 1993. Metabolism of caffeine and other components of coffee. In Caffeine, coffee and health, ed. S. Garattini, 43–95. New York: Raven.
  • Arnaud, M. J. 2011. Pharmacokinetics and metabolism of natural methylxanthines in animal and man. In Methylxanthines, 33–91. Berlin: Springer Berlin Heidelberg.
  • Asaad, N. A., Z. C. Zeng, J. Guan, J. Thacker, and G. Iliakis. 2000. Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants. Oncogene 19:5788–800. doi:10.1038/sj.onc.1203953.
  • Ascherio, A., S. M. Zhang, M. A. Hernán, I. Kawachi, G. A. Colditz, F. E. Speizer, and W. C. Willett. 2001. Prospective study of caffeine consumption and risk of Parkinson's disease in men and women. Annals of Neurology 50:56–63. doi:10.1002/ana.1052.
  • Ashihara, H., and A. Crozier. 1999. Biosynthesis and metabolism of caffeine and related purine alkaloids in plants. In Advances in botanical research, ed. J. A. Callow, 117–205. London, UK: Academic Press.
  • Ashihara, H., H. Sano, and A. Crozier. 2008. Caffeine and related purine alkaloids: Biosynthesis, catabolism, function and genetic engineering. Phytochemistry 69:841–56. doi:10.1016/j.phytochem.2007.10.029.
  • Ashihara, H., and T. Suzuki. 2004. Distribution and biosynthesis of caffeine in plants. Frontiers in Bioscience: A Journal and Virtual Library 9:1864–76. doi:10.2741/1367.
  • Assmann, G., and A. M. Gotto. 2004. HDL cholesterol and protective factors in atherosclerosis. Circulation 109:III-8-III-14. doi:10.1161/01.CIR.0000131512.50667.46.
  • Association, A. D. 2010. Diagnosis and classification of Diabetes Mellitus. Diabetes Care 33:S62–69. doi:10.2337/dc10-S062.
  • Atawodi, S. E.-o., B. Pfundstein, R. Haubner, B. Spiegelhalder, H. Bartsch, and R. W. Owen. 2007. Content of polyphenolic compounds in the nigerian stimulants Cola nitida ssp. alba, Cola nitida ssp. rubra A. Chev, and Cola acuminata Schott & Endl and their antioxidant capacity. Journal of Agricultural and Food Chemistry 55:9824–28. doi:10.1021/jf0721038.
  • Ates, N., D. Sahin, and G. Ilbay. 2004. Theophylline, a methylxanthine derivative, suppresses absence epileptic seizures in WAG/Rij rats. Epilepsy & Behavior 5:645–48. doi:10.1016/j.yebeh.2004.06.001.
  • Azam, S., N. Hadi, N. U. Khan, and S. M. Hadi. 2003. Antioxidant and prooxidant properties of caffeine, theobromine and xanthine. Medical Science Monitor: International Medical Journal of Experimenta and Clinical Research 9:BR325–330.
  • Baba, S., N. Osakabe, Y. Kato, M. Natsume, A. Yasuda, T. Kido, K. Fukuda, Y. Muto, and K. Kondo. 2007. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. The American Journal of Clinical Nutrition 85:709–17. doi:10.1093/ajcn/85.3.709.
  • Babu, E., M. Takeda, S. Narikawa, Y. Kobayashi, T. Yamamoto, S. H. Cha, T. Sekine, D. Sakthisekaran, and H. Endou. 2002. Human organic anion transporters mediate the transport of tetracycline. The Japanese Journal of Pharmacology 88:69–76. doi:10.1254/jjp.88.69.
  • Baggott, M. J., E. Childs, A. B. Hart, E. de Bruin, A. A. Palmer, J. E. Wilkinson, and H. de Wit. 2013. Psychopharmacology of theobromine in healthy volunteers. Psychopharmacology 228:109–18. doi:10.1007/s00213-013-3021-0.
  • Banerjee, P., Z. Ali, B. Levine, and D. R. Fowler. 2014. Fatal caffeine intoxication: A series of eight cases from 1999 to 2009. Journal of Forensic Sciences 59:865–68. doi:10.1111/1556-4029.12387.
  • Barcz, E., E. Sommer, P. Janik, L. Marianowski, and E. Skopinska-Rózewska. 2000. Adenosine receptor antagonism causes inhibition of angiogenic activity of human ovarian cancer cells. Oncology Reports 7:1285–91.
  • Barcz, E., E. Sommer, I. Sokolnicka, K. Gawrychowski, K. Roszkowska-Purska, P. Janik, and E. Skopinska-Rózewska. 1998. The influence of theobromine on angiogenic activity and proangiogenic cytokines production of human ovarian cancer cells. Oncology Reports 5:517–37.
  • Barnes, P., and R. Pauwels. 1994. Theophylline in the management of asthma: Time for reappraisal?. European Respiratory Journal 7:579–91. doi:10.1183/09031936.94.07030579.
  • Barnes, P. J. 2005. Theophylline in chronic obstructive pulmonary disease: new horizons. Proceedings of the American Thoracic Society 2:334–39. doi:10.1513/pats.200504-024SR.
  • Barnes, P. J. 2006. Theophylline for COPD. Thorax 61:742–44. doi:10.1136/thx.2006.061002.
  • Barnes, P. J. 2013. Theophylline. American Journal of Respiratory and Critical Care Medicine 188:901–6. doi:10.1164/rccm.201302-0388PP.
  • Barr, H. M., and A. P. Streissguth. 1991. Caffeine use during pregnancy and child outcome: A 7-year prospective study. Neurotoxicology and Teratology 13:441–48. doi:10.1016/0892-0362(91)90093-C.
  • Basu, S., and R. Mitra Basu. 2000. Theophylline as a therapy for chronic lymphocytic leukemia: a case report and review of literature. Haematologia 30:225–27. doi:10.1163/156855900300109242.
  • Batterman, R. C., A. J. Grossman, J. Schwimmer, and A. L. Blackman. 1955. TReatment of congestive heart failure and anginal syndrome with choline theophyllinate. Journal of the American Medical Association 157:234–37. doi:10.1001/jama.1955.02950200032010.
  • Batterman, R. G., A. J. Grossman, J. Dubinsky, and G. Mouratoff. 1959. Reevaluation of the usefullness of theobromine calcium gluconate for the management of congestive heart failure and anginal syndrome. International Record of Medicine and General Practice Clinics 172:318–23.
  • Baumann, T. W., B. H. Schulthess, and K. Hänni. 1995. Guaraná (Paullinia cupana) rewards seed dispersers without intoxicating them by caffeine. Phytochemistry 39:1063–70. doi:10.1016/0031-9422(94)00141-F.
  • Beale, J. M., Jr. 2011. Wilson and Gisvold's Textbook of organic medicinal and pharmaceutical chemistry. 12th Ed. Baltimore: Lippincott Williams & Wilkins, Wolters Kuwer.
  • Beaumont, M., D. Batéjat, O. Coste, P. Doireau, F. Chauffard, M. Enslen, D. Lagarde, and C. Pierard. 2005. Recovery after prolonged sleep deprivation: Residual effects of slow-release caffeine on recovery sleep, sleepiness and cognitive functions. Neuropsychobiology 51:16–27. doi:10.1159/000082851.
  • Beavo, J. A., N. L. Rogers, O. B. Crofford, J. G. Hardman, E. W. Sutherland, and E. V. Newman. 1970. Effects of xanthine derivatives on lipolysis and on adenosine 3′,5′-monophosphate phosphodiesterase activity. Molecular Pharmacology 6:597–603.
  • Bech, B. H., and R. Bossi. 2015. Simultaneous determination of methylxanthines and cotinine in human plasma by solid-phase extraction followed by LC–MS-MS. Spectroscopy 27:31–34.
  • Bech, B. H., C. Obel, T. B. Henriksen, and J. Olsen. 2007. Effect of reducing caffeine intake on birth weight and length of gestation: randomised controlled trial. BMJ: British Medical Journal 334:409. doi:10.1136/bmj.39062.520648.BE.
  • Becker, A. B., K. J. Simons, C. A. Gillespie, and F. E. R. Simons. 1984. The bronchodilator effects and pharmacokinetics of caffeine in asthma. New England Journal of Medicine 310:743–46. doi:10.1056/NEJM198403223101202.
  • Begas, E., E. Kouvaras, A. Tsakalof, S. Papakosta, and E. K. Asprodini. 2007. In vivo evaluation of CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a Greek population sample by the RP-HPLC monitoring of caffeine metabolic ratios. Biomedical Chromatography 21:190–200. doi:10.1002/bmc.736.
  • Bell, M., E. Jackson, Z. Mi, J. McCombs, and J. Carcillo. 1998. Low-dose theophylline increases urine output in diuretic-dependent critically ill children. Intensive Care Medicine 24:1099–105. doi:10.1007/s001340050723.
  • Belščak, A., D. Komes, D. Horžić, K. K. Ganić, and D. Karlović. 2009. Comparative study of commercially available cocoa products in terms of their bioactive composition. Food Research International 42:707–16. doi:10.1016/j.foodres.2009.02.018.
  • Benditt, D. G., D. W. J. Benson, J. Kreitt, A. Dunnigan, M. R. Pritzker, L. Crouse, and M. M. Scheinman. 1983. Electrophysiologic effects of theophylline in young patients with recurrent symptomatic bradyarrhythmias. American Journal of Cardiology 52:1223–29. doi:10.1016/0002-9149(83)90578-7.
  • Bendriss, E.-k., N. Markoglou, and I. W. Wainer. 2000. Liquid chromatographic method for the simultaneous determination of caffeine and fourteen caffeine metabolites in urine. Journal of Chromatography B: Biomedical Sciences and Applications 746:331–38. doi:10.1016/S0378-4347(00)00325-X.
  • Benedetti, M. D., J. H. Bower, D. M. Maraganore, S. K. McDonnell, B. J. Peterson, J. E. Ahlskog, D. J. Schaid, and W. A. Rocca. 2000. Smoking, alcohol, and coffee consumption preceding Parkinson's disease: a case-control study. Neurology 55:1350–58. doi:10.1212/WNL.55.9.1350.
  • Benowitz, N. L., P. Jacob, H. Mayan, and C. Denaro. 1995. Sympathomimetic effects of paraxanthine and caffeine in humans. Clinical Pharmacology & Therapeutics 58:684–91. doi:10.1016/0009-9236(95)90025-X.
  • Bhatia, J. 2000. Current options in the management of apnea of prematurity. Clinical Pediatrics 39:327–36. doi:10.1177/000992280003900602.
  • Bhupathiraju, S. N., A. Pan, V. S. Malik, J. E. Manson, W. C. Willett, R. M. van Dam, and F. B. Hu. 2013. Caffeinated and caffeine-free beverages and risk of type 2 diabetes. The American Journal of Clinical Nutrition 97:155–66. doi:10.3945/ajcn.112.048603.
  • Bidel, S., G. Hu, Q. Qiao, P. Jousilahti, R. Antikainen, and J. Tuomilehto. 2006. Coffee consumption and risk of total and cardiovascular mortality among patients with type 2 diabetes. Diabetologia 49:2618–26. doi:10.1007/s00125-006-0435-9.
  • Biessels, G. J. 2010. Caffeine, diabetes, cognition, and dementia. Journal of Alzheimers Disease: JAD 20:S143–50. doi:10.3233/JAD-2010-091228.
  • Blanchard, J., and S. J. A. Sawers. 1983. The absolute bioavailability of caffeine in man. European Journal of Clinical Pharmacology 24:93–98. doi:10.1007/BF00613933.
  • Block, W. D., D. Merkle, K. Meek, and S. P. Lees-Miller. 2004. Selective inhibition of the DNA-dependent protein kinase (DNA-PK) by the radiosensitizing agent caffeine. Nucleic Acids Research 32:1967–72. doi:10.1093/nar/gkh508.
  • Bode, A. M., and Z. Dong. 2007. The enigmatic effects of caffeine in cell cycle and cancer. Cancer letters 247:26–39. doi:10.1016/j.canlet.2006.03.032.
  • Bohn, S. K., N. C. Ward, J. M. Hodgson, and K. D. Croft. 2012. Effects of tea and coffee on cardiovascular disease risk. Food & Function 3:575–91. doi:10.1039/c2fo10288a.
  • Bonati, M., R. Latini, F. Galletti, J. F. Young, G. Tognoni, and S. Garattini. 1982. Caffeine disposition after oral doses. Clinical Pharmacology & Therapeutics 32:98–106. doi:10.1038/clpt.1982.132.
  • Bray, G. A., S. Mothon, and A. S. Cohen. 1970. Mobilization of fatty acids in genetically obese rats. Journal of Lipid Research 11:517–21.
  • Brent, R. L., M. S. Christian, and R. M. Diener. 2011. Evaluation of the reproductive and developmental risks of caffeine. Birth Defects Research. Part B, Developmental and Reproductive Toxicology 92:152–87. doi:10.1002/bdrb.20288.
  • Brice, C. F., and A. P. Smith. 2002. Effects of caffeine on mood and performance: a study of realistic consumption. Psychopharmacology 164:188–92. doi:10.1007/s00213-002-1175-2.
  • Brokaw, C. J. 1987. Regulation of sperm flagellar motility by calcium and cAMP-dependent phosphorylation. Journal of Cellular Biochemistry 35:175–84. doi:10.1002/jcb.240350302.
  • Brouwers, J., F. Ingels, J. Tack, and P. Augustijns. 2005. Determination of intraluminal theophylline concentrations after oral intake of an immediate-and a slow-release dosage form. Journal of Pharmacy and Pharmacology 57:987–95. doi:10.1211/0022357056631.
  • Browne, M. L., E. M. Bell, C. M. Druschel, L. J. Gensburg, A. A. Mitchell, A. E. Lin, P. A. Romitti, and A. Correa. 2007. Maternal caffeine consumption and risk of cardiovascular malformations. Birth Defects Research Part A: Clinical and Molecular Teratology 79:533–43. doi:10.1002/bdra.20365.
  • Browne, M. L., A. T. Hoyt, M. L. Feldkamp, S. A. Rasmussen, E. G. Marshall, C. M. Druschel, and P. A. Romitti. 2011. Maternal caffeine intake and risk of selected birth defects in the national birth defects prevention study. Birth Defects Research Part A: Clinical and Molecular Teratology 91:93–101. doi:10.1002/bdra.20752.
  • Bush, R. S., R. D. Jenkin, W. E. Allt, F. A. Beale, H. Bean, A. J. Dembo, and J. F. Pringle. 1978. Definitive evidence for hypoxic cells influencing cure in cancer therapy. The British Journal of Cancer. Supplement 3:302–306.
  • Busse, P. M., S. K. Bose, R. W. Jones, and L. J. Tolmach. 1978. The action of caffeine on X-Irradiated HeLa cells: III. Enhancement of X-ray-induced killing during G2 arrest. Radiation Research 76:292–307. doi:10.2307/3574780.
  • Butcher, R. W., and E. W. Sutherland. 1962. Adenosine 3′,5′-Phosphate in Biological Materials: I. Purification and properties of cyclic 3′,5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′,5′-phosphate in human urine. Journal of Biological Chemistry 237:1244–50.
  • Butts, J. D., B. Secrest, and R. Berger. 1991. Nonlinear theophylline pharmacokinetics: A preventable cause of latrogenic theophylline toxic reactions. Archives of Internal Medicine 151:2073–77. doi:10.1001/archinte.1991.00400100137023.
  • Byfield, J. E., J. Murnane, J. F. Ward, P. Calabro-Jones, M. Lynch, and F. Kulhanian. 1981. Mice, men, mustard and methylated xanthines: the potential role of caffeine and related drugs in the sensitization of human tumours to alkylating agents. British Journal of Cancer 43:669–83. doi:10.1038/bjc.1981.98.
  • Cameron, O. G., J. G. Modell, and M. Hariharan. 1990. Caffeine and human cerebral blood flow: a positron emission tomography study. Life Sciences 47:1141–46. doi:10.1016/0024-3205(90)90174-P.
  • Cao, C., J. R. Cirrito, X. Lin, L. Wang, D. K. Verges, A. Dickson, M. Mamcarz, C. Zhang, T. Mori, G. W. Arendash, D. M. Holtzman, and H. Potter. 2009. Caffeine suppresses β-amyloid levels in plasma and brain of Alzheimer's transgenic mice. Journal of Alzheimer's disease: JAD 17:681–97. doi:10.3233/JAD-2009-1071.
  • Cao, C., D. A. Loewenstein, X. Lin, C. Zhang, L. Wang, R. Y. W. Duara, A. Giannini, G. Bai, J. Cai, M. Greig, E. Schofield, R. Ashok, B. Small, H. Potter, and G. W. Arendash. 2012. High Blood caffeine levels in MCI linked to lack of progression to dementia. Journal of Alzheimers Disease: JAD 30:559–72.
  • Cappelletti, S., P. Daria, G. Sani, and M. Aromatario. 2015. Caffeine: Cognitive and physical performance enhancer or psychoactive drug? Current Neuropharmacology 13:71–88. doi:10.2174/1570159X13666141210215655.
  • Cardinali, D. P. 1980. Methylxanthines: possible mechanisms of action in brain. Trends in pharmacological sciences 1:405–7. doi:10.1016/0165-6147(80)90064-4.
  • Carman, A. J., P. A. Dacks, R. F. Lane, D. W. Shineman, and H. M. Fillit. 2014. Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer's disease. The journal of nutrition, health & aging 18:383–92. doi:10.1007/s12603-014-0021-7.
  • Carvalho, M., C. Jerónimo, P. Valentão, P. B. Andrade, and B. M. Silva. 2010. Green tea: A promising anticancer agent for renal cell carcinoma. Food Chemistry 122:49–54. doi:10.1016/j.foodchem.2010.02.014.
  • Caudle, A. G., Y. Gu, and L. N. Bell. 2001. Improved analysis of theobromine and caffeine in chocolate food products formulated with cocoa powder. Food Research International 34:599–603. doi:10.1016/S0963-9969(01)00077-1.
  • Cawley, M. J., A. S. Al-Jazairi, and E. A. Stone. 2001. Intravenous theophylline — An alternative to temporary pacing in the management of bradycardia secondary to AV nodal block. Annals of Pharmacotherapy 35:303–7. doi:10.1345/aph.10106.
  • Chantre, P., and D. Lairon. 2002. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine 9:3–8. doi:10.1078/0944-7113-00078.
  • Chapman, R. F., and T. D. Mickleborough. 2009. The effects of caffeine on ventilation and pulmonary function during exercise: An often-overlooked response. The Physician and Sportsmedicine 37:97–103. doi:10.3810/psm.2009.12.1747.
  • Chardon, K., V. Bach, F. Telliez, V. Cardot, P. Tourneux, A. Leke, and J.-P. Libert. 2004. Effect of caffeine on peripheral chemoreceptor activity in premature neonates: interaction with sleep stages. Journal of Applied Physiology 96:2161–66. doi:10.1152/japplphysiol.01160.2003.
  • Chen, J.-F., and Y. Chern. 2011. Impacts of methylxanthines and adenosine receptors on neurodegeneration: Human and experimental studies. In Methylxanthines, 267–310. Berlin: Springer Berlin Heidelberg.
  • Chen, J. F., K. Xu, J. P. Petzer, R. Staal, Y. H. Xu, M. Beilstein, P. K. Sonsalla, K. Castagnoli, N. J. Castagnoli, and M. A. Schwarzschild. 2001. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease. The Journal of Neuroscience 21 (RC143):141–46.
  • Chen, L., E. M. Bell, M. L. Browne, C. M. Druschel, P. A. Romitti, R. J. Schmidt, T. L. Burns, R. Moslehi, R. S. Olney. 2012. Maternal caffeine consumption and risk of congenital limb deficiencies. Birth defects research. Part A, Clinical and molecular teratology 94:1033–43. doi:10.1002/bdra.23050.
  • Chen, X., J. W. Gawryluk, J. F. Wagener, O. Ghribi, and J. D. Geiger. 2008a. Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease. Journal of Neuroinflammation 5:12–12. doi:10.1186/1742-2094-5-12.
  • Chen, X., X. Lan, I. Roche, R. Liu, and J. D. Geiger. 2008b. Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum. Journal of Neurochemistry 107:1147–57.
  • Childs, E., and H. Wit. 2006. Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users. Psychopharmacology 185:514–23. doi:10.1007/s00213-006-0341-3.
  • Choi, O. H., M. T. Shamim, W. L. Padgett, and J. W. Daly. 1988. Caffeine and theophylline analogues: Correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors. Life Sciences 43:387–98. doi:10.1016/0024-3205(88)90517-6.
  • Chorostowska-Wynimko, J., E. Skopińska-Rózewska, E. Sommer, E. Rogala, P. Skopiński, and E. Wojtasik. 2004. Multiple effects of theobromine on fetus development and postnatal status of the immune system. International Journal of Tissue Reactions 26:53–60.
  • Chu, Y.-F., W.-H. Chang, R. M. Black, J.-R. Liu, P. Sompol, Y. Chen, H. Wei, Q. Zhao, and I. H. Cheng. 2012. Crude caffeine reduces memory impairment and amyloid β1–42 levels in an Alzheimer's mouse model. Food Chemistry 135:2095–102. doi:10.1016/j.foodchem.2012.04.148.
  • Chung, F.-L., M. Wang, A. Rivenson, M. J. Iatropoulos, J. C. Reinhardt, B. Pittman, C.-T. Ho, and S. G. Amin. 1998. Inhibition of lung carcinogenesis by black tea in fischer rats treated with a tobacco-specific carcinogen: Caffeine as an important constituent. Cancer Research 58:4096–101.
  • Chvasta, T. E., and A. R. Cooke. 1971. Emptying and absorption of caffeine from the human stomach. Gastroenterology 61:838–43.
  • Cirillo, R., D. Barone, and J. S. Franzone. 1987. Doxofylline, an antiasthmatic drug lacking affinity for adenosine receptors. Archives internationales de pharmacodynamie et de thérapie 295:221–37.
  • Clauson, K. A., K. M. Shields, C. E. McQueen, and N. Persad. 2008. Safety issues associated with commercially available energy drinks. Journal of the American Pharmacists Association: JAPhA 48:55–67. doi:10.1331/JAPhA.2008.07055.
  • Comer, A. M., C. M. Perry, and D. P. Figgitt. 2001. Caffeine citrate: a review of its use in apnoea of prematurity. Paediatric Drugs 3:61–79. doi:10.2165/00128072-200103010-00005.
  • Conde, V. R., M. G. Alves, P. F. Oliveira, and B. M. Silva. 2015. Tea (Camellia sinensis (L.)): A putative anticancer agent in bladder carcinoma?. Anti-Cancer Agents in Medicinal Chemistry 15:26–36. doi:10.2174/1566524014666141203143143.
  • Cooper, R. 2012. Green tea and theanine: Health benefits. International Journal of Food Sciences and Nutrition 63:90–97. doi:10.3109/09637486.2011.629180.
  • Cosio, B. G., L. Tsaprouni, K. Ito, E. Jazrawi, I. M. Adcock, and P. J. Barnes. 2004. Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. The Journal of Experimental Medicine 200:689–95. doi:10.1084/jem.20040416.
  • Costa, J., N. Lunet, C. Santos, J. Santos, and A. Vaz-Carneiro. 2010. Caffeine exposure and the risk of Parkinson's disease: a systematic review and meta-analysis of observational studies. Journal of Alzheimers Disease: JAD 20:S221–38. doi:10.3233/JAD-2010-091525.
  • Coulson, R., and S. J. Scheinman. 1989. Xanthine effects on renal proximal tubular function and cyclic AMP metabolism. Journal of Pharmacology and Experimental Therapeutics 248:589–95.
  • Cunha, R. A. 2005. Neuroprotection by adenosine in the brain: From A(1) receptor activation to A(2A) receptor blockade. Purinergic Signalling 1:111–34. doi:10.1007/s11302-005-0649-1.
  • Cunha, R. A. 2008. Caffeine, adenosine receptors, memory and Alzheimer disease. Medicina Clínica 131:790–95. doi:10.1016/S0025-7753(08)75506-4.
  • Czok, G. 1974. Concerning the question of the biological effectiveness of methylxanthines in cocoa products. Zeitschrift für Ernährungswissenschaft 4:165–70. doi:10.1007/BF02021187.
  • D'Urzo, A. D., R. Jhirad, H. Jenne, M. A. Avendano, I. Rubinstein, M. D'Costa, R. S. Goldstein, and I. Rubenstein. 1990. Effect of caffeine on ventilatory responses to hypercapnia, hypoxia, and exercise in humans. Journal of Applied Physiology 68:322–28. doi:10.1152/jappl.1990.68.1.322.
  • Dall'Igna, O. P., P. Fett, M. W. Gomes, D. O. Souza, R. A. Cunha, and D. R. Lara. 2007. Caffeine and adenosine A2a receptor antagonists prevent β-amyloid (25–35)-induced cognitive deficits in mice. Experimental Neurology 203:241–45. doi:10.1016/j.expneurol.2006.08.008.
  • Dall'lgna, O. P., L. O. Porciúncula, D. O. Souza, R. A. Cunha, and D. R. Lara. 2003. Neuroprotection by caffeine and adenosine A(2A) receptor blockade of β-amyloid neurotoxicity. British Journal of Pharmacology 138:1207–1209. doi:10.1038/sj.bjp.0705185.
  • Daly, J. W. 2000. Alkylxanthines as research tools. Journal of the Autonomic Nervous System 81:44–52. doi:10.1016/S0165-1838(00)00110-7.
  • Daly, J. W. 2007. Caffeine analogs: Biomedical impact. Cellular and Molecular Life Sciences 64:2153–69. doi:10.1007/s00018-007-7051-9.
  • Daly, J. W., W. Padgett, M. T. Shamim, P. Butts-Lamb, and J. Waters. 1985. 1,3-Dialkyl-8-(p-sulfophenyl)xanthines: potent water-soluble antagonists for A1- and A2-adenosine receptors. Journal of Medicinal Chemistry 28:487–92. doi:10.1021/jm00382a018.
  • Dambrosio, S. M. 1994. Evaluation of the genotoxicity data on caffeine. Regulatory Toxicology and Pharmacology 19:243–81. doi:10.1006/rtph.1994.1023.
  • Davis, J. O., and N. W. Shock. 1949. The effect of theophylline ethylene diamine on renal function in control subjects and in patients with congestive heart failure. Journal of Clinical Investigation 28:1459–68. doi:10.1172/JCI102211.
  • DeLago, A., M. El-Hajjar, and M. Kirnus. 2008. Aminophylline for prevention of bradyarrhythmias induced by rheolytic thrombectomy. The Journal of Invasive Cardiology 20:9A–11A.
  • Dent, G., M. A. Giembycz, K. F. Rabe, B. Wolf, P. J. Barnes, and H. Magnussen. 1994. Theophylline suppresses human alveolar macrophage respiratory burst through phosphodiesterase inhibition. American Journal of Respiratory Cell and Molecular Biology 10:565–72. doi:10.1165/ajrcmb.10.5.8179921.
  • Derry, C. J., S. Derry, and R. A. Moore. 2014. Caffeine as an analgesic adjuvant for acute pain in adults. The Cochrane Database of Systematic Reviews 12:1–62.
  • Dias, T. R., M. G. Alves, R. L. Bernardino, A. D. Martins, A. C. Moreira, J. Silva, A. Barros, M. Sousa, B. M. Silva, and P. F. Oliveira. 2015. Dose-dependent effects of caffeine in human Sertoli cells metabolism and oxidative profile: Relevance for male fertility. Toxicology 328:12–20. doi:10.1016/j.tox.2014.12.003.
  • Dias, T. R., M. G. Alves, G. D. Tomás, S. Socorro, B. M. Silva, and P. F. Oliveira. 2014. White tea as a promising antioxidant medium additive for sperm storage at room temperature: A comparative study with green tea. Journal of Agricultural and Food Chemistry 62:608–17. doi:10.1021/jf4049462.
  • Dieren, S., C. S. P. M. Uiterwaal, Y. T. Schouw, D. L. A, J. M. A. Boer, A. Spijkerman, D. E. Grobbee, and J. W. J. Beulens. 2009. Coffee and tea consumption and risk of type 2 diabetes. Diabetologia 52:2561–69. doi:10.1007/s00125-009-1516-3.
  • Ding, M., S. N. Bhupathiraju, M. Chen, R. M. van Dam, and F. B. Hu. 2014a. Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: A systematic review and a dose-response meta-analysis. Diabetes Care 37:569–86. doi:10.2337/dc13-1203.
  • Ding, M., S. N. Bhupathiraju, A. Satija, R. M. van Dam, and F. B. Hu. 2014b. Long-term coffee consumption and risk of cardiovascular disease: A systematic review and a dose-response meta-analysis of prospective cohort studies. Circulation 129:643–59. doi:10.1161/CIRCULATIONAHA.113.005925.
  • Dini, F. L., and R. Cogo. 2001. Doxofylline: a new generation xanthine bronchodilator devoid of major cardiovascular adverse effects. Current Medical Research and Opinion 16:258–68. doi:10.1185/030079901750120196.
  • Dische, S., P. J. Anderson, R. Sealy, and E. R. Watson. 1983. Carcinoma of the cervix—anaemia, radiotherapy and hyperbaric oxygen. The British Journal of Radiology 56:251–55. doi:10.1259/0007-1285-56-664-251.
  • Dohle, G. R., G. M. Colpi, T. B. Hargreave, G. K. Papp, A. Jungwirth, and W. Weidner. 2005. EAU guidelines on male infertility. European Urology 48:703–11. doi:10.1016/j.eururo.2005.06.002.
  • Doré, A. S., N. Robertson, J. C. Errey, I. Ng, K. Hollenstein, B. Tehan, E. Hurrell, K. Bennett, M. Congreve, F. Magnani, C. G. Tate, M. Weir, and F. H. Marshall. 2011. Structure of the adenosine A(2A) receptor in complex with ZM241385 and the xanthines XAC and caffeine. Structure (London, England: 1993) 19:1283–93. doi:10.1016/j.str.2011.06.014.
  • Dragicevic, N., V. Delic, C. Cao, N. Copes, X. Lin, M. Mamcarz, L. Wang, G. W. Arendash, and P. C. Bradshaw. 2012. Caffeine increases mitochondrial function and blocks melatonin signaling to mitochondria in Alzheimer's mice and cells. Neuropharmacology 63:1368–79. doi:10.1016/j.neuropharm.2012.08.018.
  • Drouillard, D. D., E. S. Vesell, and B. H. Dvorchik. 1978. Studies on theobromine disposition in normal subjects; Alterations induced by dietary abstention from or exposure to methylxanthines. Clinical Pharmacology & Therapeutics 23:296–302. doi:10.1002/cpt1978233296.
  • Duarte, J. M. N., R. A. Carvalho, R. A. Cunha, and R. Gruetter. 2009. Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats. Journal of Neurochemistry 111:368–79. doi:10.1111/j.1471-4159.2009.06349.x.
  • Dulloo, A. G., C. Duret, D. Rohrer, L. Girardier, N. Mensi, M. Fathi, P. Chantre, and J. Vandermander. 1999. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. The American Journal of Clinical Nutrition 70:1040–45. doi:10.1093/ajcn/70.6.1040.
  • Dulloo, A. G., J. Seydoux, L. Girardier, P. Chantre, and J. Vandermander. 2000. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. International Journal of Obesity and Related Metabolic Disorders 24:252–58. doi:10.1038/sj.ijo.0801101.
  • Eichenwald, E. C., A. Aina, and A. R. Stark. 1997. Apnea frequently persists beyond term gestation in infants delivered at 24 to 28 weeks. Pediatrics 100:354–59. doi:10.1542/peds.100.3.354.
  • El-Bitar, M. K., and R.-M. N. Boustany. 2009. Common causes of uncommon seizures. Pediatric Neurology 41:83–87. doi:10.1016/j.pediatrneurol.2009.04.011.
  • El-Yazigi, A., and R. J. Sawchukx. 1981. Theophylline absorption and disposition in rabbits: Oral, intravenous, and concentration-dependent kinetic studies. Journal of Pharmaceutical Sciences 70:452–56. doi:10.1002/jps.2600700429.
  • El-Yazigi, A., S. Shabib, S. Al-Rawithi, A. Yusuf, E. S. Legayada, and A. Al-Humidan. 1999. Salivary clearance and urinary metabolic pattern of caffeine in healthy children and in pediatric patients with hepatocellular diseases. The Journal of Clinical Pharmacology 39:366–72. doi:10.1177/00912709922007930.
  • Eldridge, F. L., D. E. Millhorn, and J. P. Kiley. 1985. Antagonism by theophylline of respiratory inhibition induced by adenosine. Journal of Applied Physiology 59:1428–33. doi:10.1152/jappl.1985.59.5.1428.
  • Emara, S. 2004. Simultaneous determination of caffeine, theophylline and theobromine in human plasma by on-line solid-phase extraction coupled to reversed-phase chromatography. Biomedical Chromatography 18:479–85. doi:10.1002/bmc.341.
  • Eskelinen, M. H., T. Ngandu, J. Tuomilehto, H. Soininen, and M. Kivipelto. 2009. Midlife coffee and tea drinking and the risk of latelife dementia: a population-based CAIDE study. Journal of Alzheimers Disease: JAD 16:85–91. doi:10.3233/JAD-2009-0920.
  • Eteng, M. U., E. U. Eyong, E. O. Akpanyung, M. A. Agiang, and C. Y. Aremu. 1997. Recent advances in caffeine and theobromine toxicities: a review. Plant Foods for Human Nutrition 51:231–43. doi:10.1023/A:1007976831684.
  • Evoniuk, G., R. W. von Borstel, and R. J. Wurtman. 1987. Antagonism of the cardiovascular effects of adenosine by caffeine or 8-(p-sulfophenyl)theophylline. Journal of Pharmacology and Experimental Therapeutics 240:428–32.
  • Farooqi, Z., and P. C. Kesavan. 1992. Radioprotection by caffeine pre- and post-treatment in the bone marrow chromosomes of mice given whole-body γ-irradiation. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 269:225–30. doi:10.1016/0027-5107(92)90203-E.
  • Fenner, A., U. Schalk, H. Hoenicke, A. Wendenburg, and T. Roehling. 1973. Periodic breathing in premature and neonatal babies: Incidence, breathing pattern, respiratory gas tensions, response to changes in the composition of ambient air. Pediatr Res 7:174–83. doi:10.1203/00006450-197304000-00020.
  • Fenske, M. 2006. Caffeine determination in human saliva and urine by TLC and ultraviolet absorption densitometry. Chromatographia 65:233–38. doi:10.1365/s10337-006-0141-2.
  • Fenster, L., C. Quale, R. A. Hiatt, M. Wilson, G. C. Windham, and N. L. Benowitz. 1998. Rate of caffeine metabolism and risk of spontaneous abortion. American Journal of Epidemiology 147:503–10. doi:10.1093/oxfordjournals.aje.a009477.
  • Fingert, H. J., J. D. Chang, and A. B. Pardee. 1986. Cytotoxic, cell cycle, and chromosomal effects of methylxanthines in human tumor cells treated with alkylating agents. Cancer Research 46:2463–67.
  • Fingert, H. J., A. T. Pu, Z. Y. Chen, and A. B. Perdee. 1988. In vivo and in vitro enhanced antitumour effect by pentoxifylline in human cancer cells treated with Thiothepa. Cancer Research 48:4375–81.
  • Fleetham, J. A., C. E. Bird, K. Nakatsu, R. D. Wigle, and P. W. Munt. 1981. Dose-dependency of theophylline clearance and protein binding. Thorax 36:382–86. doi:10.1136/thx.36.5.382.
  • Fozard, J. R., and C. McCarthy. 2002. Adenosine receptor ligands as potential therapeutics in asthma. Current Opinion in Investigational Drugs 3:69–77.
  • Franco, R., A. Oñatibia-Astibia, and E. Martínez-Pinilla. 2013. Health benefits of methylxanthines in cacao and chocolate. Nutrients 5:4159–73. doi:10.3390/nu5104159.
  • Fredholm, B. B. 1985. On the mechanism of action of theophylline and caffeine. Acta Medica Scandinavica 217:149–53. doi:10.1111/j.0954-6820.1985.tb01650.x.
  • Fredholm, B. B., K. Bättig, J. Holmén, A. Nehlig, and E. E. Zvartau. 1999. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacological Reviews 51:83–133.
  • Fredholm, B. B., P. Hedqvist, and L. Vernet. 1978. Effect of theophylline and other drugs on rabbit renal cyclic nucleotide phosphodiesterase, 5′-nucleotidase and adenosine deaminase. Biochemical Pharmacology 27:2845–50. doi:10.1016/0006-2952(78)90199-5.
  • French, I. W., and C. A. Mildon. 1979. The pharmacokinetics of theophylline. Current Medical Research and Opinion 6:3–13. doi:10.1185/03007997909115902.
  • Friedman, L., M. A. Weinberger, T. M. Farber, F. M. Moreland, E. L. Peters, C. E. Gilmore, and M. A. Khan. 1979. Testicular atrophy and impaired spermatogenesis in rats fed high levels of the methylxanthines caffeine, theobromine, or theophylline. Journal of Environmental Pathology and Toxicology 2:687–706.
  • Fuhr, U., J. Doehmer, N. Battula, C. Wölfel, I. Flick, C. Kudla, Y. Keita, and A. H. Staib. 1993. Biotransformation of methylxanthines in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. Allocation of metabolic pathways to isoforms and inhibitory effects of quinolones. Toxicology. 82:169–89.
  • Fuxe, K., and U. Ungerstedt. 1974. Action of caffeine and theophyllamine on supersensitive dopamine receptors: considerable enhancement of receptor response to treatment with DOPA and dopamine receptor agonists. Medical Biology 52:48–54.
  • Gabrielli, B., Y. Q. Chau, N. Giles, A. Harding, F. Stevens, and H. Beamish. 2007. Caffeine promotes apoptosis in mitotic spindle checkpoint-arrested cells. Journal of Biological Chemistry 282:6954–64. doi:10.1074/jbc.M610104200.
  • Gaburjakova, J., and M. Gaburjakova. 2014. Coupled gating modifies the regulation of cardiac ryanodine receptors by luminal Ca2+. Biochimica et Biophysica Acta (BBA) – Biomembranes 1838:867–73. doi:10.1016/j.bbamem.2013.11.005.
  • Gans, J. H. 1984. Comparative toxicities of dietary caffeine and theobromine in the rat. Food and Chemical Toxicology 22:365–69. doi:10.1016/0278-6915(84)90365-X.
  • Gardenhire, D. S. 2016. Rau's respiratory care pharmacology. 9th Ed. St Louis: Elsevier Health Sciences.
  • Georga, K. A., V. F. Samanidou, and I. N. Papadoyannis. 2000. Improved micro-method for the HPLC analysis of caffeine and its demethylated metabolites in human biological fluids after SPE. Journal of Liquid Chromatography & Related Technologies 23:1523–37. doi:10.1081/JLC-100100432.
  • Giesbrecht, T., J. A. Rycroft, M. J. Rowson, and E. A. De Bruin. 2010. The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutricional Neuroscience 13:283–90. doi:10.1179/147683010X12611460764840.
  • Gil, M., E. Skopińska-Rózewska, D. Radomska, U. Demkow, H. Skurzak, M. Rochowska, J. Beuth, and K. Roszkowski. 1993. Effect of purinergic receptor antagonists suramin and theobromine on tumor-induced angiogenesis in BALB/c mice. Folia Biologica 39:63–68.
  • Gilbert, R. M., J. A. Marshman, M. Schwieder, and R. Berg. 1976. Caffeine content of beverages as consumed. Canadian Medical Association Journal 114:205–208.
  • Gilbert, S. G. 2004. Caffeine: Biological Properties. In A small dose of toxicology: The health effects of common chemicals, 56–58. Boca Raton: CRC (Ed.), CRC Press.
  • Ginchansky, E., and M. Weinberger. 1977. Relationship of theophylline clearance to oral dosage in children with chronic asthma. The Journal of Pediatrics 91:655–60. doi:10.1016/S0022-3476(77)80527-1.
  • Glade, M. J. 2010. Caffeine-Not just a stimulant. Nutrition 26:932–38. doi:10.1016/j.nut.2010.08.004.
  • Goldstein, M. F., and P. Chervinsky. 2002. Efficacy and safety of doxofylline compared to theophylline in chronic reversible asthma-a double-blind randomized placebo-controlled multicentre clinical trial. Medical Science Monitor 8:CR297–304.
  • Gołembiowska, K., J. Wardas, K. Noworyta-Sokołowska, K. Kamińska, and A. Górska. 2013. Effects of adenosine receptor antagonists on the in vivo LPS-induced inflammation model of Parkinson's disease. Neurotoxicity Research 24:29–40. doi:10.1007/s12640-012-9372-1.
  • Gonçalves, N., A. T. Simões, R. A. Cunha, and L. P. de Almeida. 2013. Caffeine and adenosine A2A receptor inactivation decrease striatal neuropathology in a lentiviral-based model of Machado–Joseph disease. Annals of Neurology 73:655–66. doi:10.1002/ana.23866.
  • Graham, T. E., and L. L. Spriet. 1991. Performance and metabolic responses to a high caffeine dose during prolonged exercise. Journal of Applied Physiology 71:2292–98. doi:10.1152/jappl.1991.71.6.2292.
  • Grandjean, A. C., K. J. Reimers, K. E. Bannick, and M. C. Haven. 2000. The effect of caffeinated, non-caffeinated, caloric and non-caloric beverages on hydration. Journal of the American College of Nutrition 19:591–600. doi:10.1080/07315724.2000.10718956.
  • Greer, F., D. Friars, and T. E. Graham. 2000. Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance. Journal of Applied Physiology 89:1837–44. doi:10.1152/jappl.2000.89.5.1837.
  • Greer, F., R. Hudson, R. Ross, and T. Graham. 2001. Caffeine ingestion decreases glucose disposal during a hyperinsulinemic-euglycemic clamp in sedentary humans. Diabetes 50:2349–54. doi:10.2337/diabetes.50.10.2349.
  • Grosso, L. M., and M. B. Bracken. 2005. Caffeine metabolism, genetics, and perinatal outcomes: A review of exposure assessment considerations during pregnancy. Annals of Epidemiology 15:460–66. doi:10.1016/j.annepidem.2004.12.011.
  • Group, C. S. 2008. Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study. BMJ: British Medical Journal 337:a2332. doi:10.1136/bmj.a2332.
  • Grucka-Mamczar, E., J. Zalejska-Fiolka, D. Chlubek, S. Kasperczyk, U. Blaszczyk, A. Kasperczyk, E. Swietochowska, and E. Birkner. 2009. The influence of sodium fluoride and caffeine on the activity of antioxidative enzymes and the concentration of malondialdehyde in rat liver. Fluoride 42:105–9.
  • Gude, R. P., L. G. Menon, and S. G. Rao. 2001. Effect of Caffeine, a xanthine derivative, in the inhibition of experimental lung metastasis induced by B16F10 melanoma cells. Journal of Experimental & Clinical Cancer Research 20:287–92.
  • Guerreiro, S., D. Toulorge, E. Hirsch, M. Marien, P. Sokoloff, and P. P. Michel. 2008. Paraxanthine, the primary metabolite of caffeine, provides protection against dopaminergic cell death via stimulation of ryanodine receptor channels. Molecular Pharmacology 74:980–89. doi:10.1124/mol.108.048207.
  • Han, M.-E., H.-J. Kim, Y.-S. Lee, D.-H. Kim, J.-T. Choi, C.-S. Pan, S. Yoon, S.-Y. Baek, B.-S. Kim, J.-B. Kim, and S.-O. Oh. 2009. Regulation of cerebrospinal fluid production by caffeine consumption. BMC Neuroscience 10:110–10. doi:10.1186/1471-2202-10-110.
  • Hart, A. B., H. de Wit, and A. A. Palmer. 2012. Genetic factors modulating the response to stimulant drugs in humans. Current topics in behavioral neurosciences 12:537–77. doi:10.1007/7854_2011_187.
  • Hashimoto, T., Z. He, W.-Y. Ma, P. C. Schmid, A. M. Bode, C. S. Yang, and Z. Dong. 2004. Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells. Cancer Research 64:3344–49. doi:10.1158/0008-5472.CAN-03-3453.
  • Haskell, C. F., D. O. Kennedy, K. A. Wesnes, and A. B. Scholey. 2005. Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine. Psychopharmacology 179:813–25. doi:10.1007/s00213-004-2104-3.
  • Hayashi, M., H. Tsuchiya, N. Yamamoto, M. Karita, T. Shirai, H. Nishida, A. Takeuchi, and K. Tomita. 2005. Caffeine-potentiated chemotherapy for metastatic carcinoma and lymphoma of bone and soft tissue. Anticancer Research 25:2399–405.
  • Heath, A., and K. Knudsen. 1987. Role of extracorporeal drug removal in acute theophylline poisoning. Medical Toxicology and Adverse Drug Experience 2:294–308.
  • Hebbar, S. A., A. K. Mitra, K. C. George, and N. C. Verma. 2002. Caffeine ameliorates radiation-induced skin reactions in mice but does not influence tumour radiation response. Journal of Radiological Protection 22:63. doi:10.1088/0952-4746/22/1/306.
  • Hedner, T., J. Hedner, B. Bergman, R. A. Mueller, and J. Jonason. 1985. Characterization of adenosine-induced respiratory depression in the preterm rabbit. Biology of the Neonate 47:323–32. doi:10.1159/000242135.
  • Hendeles, L., and M. Weinberger. 1983. Theophylline: A “state of the art” review. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 3:2–44. doi:10.1002/j.1875-9114.1983.tb04531.x.
  • Henderson-Smart, D. J., and A. G. De Paoli. 2010. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database of Systematic Reviews 8:CD000140.
  • Heppel, L. A., V. T. Porterfield, and E. G. Peake. 1947. The lipotropic activity of caffeine, theobromine and theophylline. Archives of Biochemistry and Biophysics 15:439–43.
  • Herlenius, E., and H. Lagercrantz. 1999. Adenosinergic modulation of respiratory neurones in the neonatal rat brainstem in vitro. The Journal of Physiology 518:159–72. doi:10.1111/j.1469-7793.1999.0159r.x.
  • Herman, A., and A. P. Herman. 2013. Caffeine's mechanisms of action and its cosmetic use. Skin Pharmacology and Physiology 26:8–14. doi:10.1159/000343174.
  • Hirsh, L., A. Dantes, B.-S. Suh, Y. Yoshida, K. Hosokawa, K. Tajima, F. Kotsuji, O. Merimsky, and A. Amsterdam. 2004. Phosphodiesterase inhibitors as anti-cancer drugs. Biochemical Pharmacology 68:981–88. doi:10.1016/j.bcp.2004.05.026.
  • Hofstetter, A. O., L. Legnevall, E. Herlenius, and M. Katz-Salamon. 2008. Cardiorespiratory development in extremely preterm infants: vulnerability to infection and persistence of events beyond term-equivalent age. Acta Pædiatrica 97:285–92. doi:10.1111/j.1651-2227.2007.00618.x.
  • Hoyt, A. T., M. Browne, S. Richardson, P. Romitti, and C. Druschel. 2013. Maternal caffeine consumption and small for gestational age births: Results from a population-based case–control study. Maternal and Child Health Journal 18:1540–51. doi:10.1007/s10995-013-1397-4.
  • Huang, M.-T., J.-G. Xie, Z. Y. Wang, C.-T. Ho, Y.-R. Lou, C.-X. Wang, G. C. Hard, and A. H. Conney. 1997. Effects of tea, decaffeinated tea, and caffeine on UVB light-induced complete carcinogenesis in SKH-1 mice: Demonstration of caffeine as a biologically important constitutent of tea. Cancer Research 57:2623–29.
  • Huber, L. G. 2003. Green tea catechins and L-theanine in integrative cancer care: A review of the research. Alternative and Complementary Therapies 9:294–98. doi:10.1089/107628003322658557.
  • Huck, C. W., W. Guggenbichler, and G. K. Bonn. 2005. Analysis of caffeine, theobromine and theophylline in coffee by near infrared spectroscopy (NIRS) compared to high-performance liquid chromatography (HPLC) coupled to mass spectrometry. Analytica Chimica Acta 538:195–203. doi:10.1016/j.aca.2005.01.064.
  • Hulbert, G. J., R. N. Biswal, C. B. Mehr, T. H. Walker, and J. L. Collins. 1998. Solid/liquid extraction of caffeine from guaraná with methylene chloride/Extracción solido-liquido de cafeina de guarana con cloruro de metileno. Food Science and Technology International 4:53–58. doi:10.1177/108201329800400107.
  • Hull, M. G., C. M. Glazener, N. J. Kelly, D. I. Conway, P. A. Foster, R. A. Hinton, C. Coulson, P. A. Lambert, E. M. Watt, and K. M. Desai. 1985. Population study of causes, treatment, and outcome of infertility. British Medical Journal (Clinical research ed.) 291:1693–97. doi:10.1136/bmj.291.6510.1693.
  • Iliakis, G., M. Nusse, R. Ganapathi, J. Egner, and A. Yen. 1986. Differential reduction by caffeine of adriamycin induced cell killing and cell cycle delays in chinese hamster v79 cells. International Journal of Radiation Oncology 12:1987–95. doi:10.1016/0360-3016(86)90136-7.
  • Inoue, H., K. Kobayashi-Hattori, Y. Horiuchi, Y. Oishi, S. Arai, and T. Takita. 2006. Regulation of the body fat percentage in developmental-stage rats by methylxanthine derivatives in a high-fat diet. Bioscience, Biotechnology, and Biochemistry 70:1134–39. doi:10.1271/bbb.70.1134.
  • Ito, K., S. Lim, G. Caramori, B. Cosio, K. F. Chung, I. M. Adcock, and P. J. Barnes. 2002. A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proceedings of the National Academy of Sciences of the United States of America 99:8921–26. doi:10.1073/pnas.132556899.
  • Izzo, J. L., Jr., A. Ghosal, T. Kwong, R. B. Freeman, and J. R. Jaenike. 1983. Age and prior caffeine use alter the cardiovascular and adrenomedullary responses to oral caffeine. American Journal of Cardiology 52:769–73. doi:10.1016/0002-9149(83)90413-7.
  • Jackman, M., P. Wendling, D. Friars, and T. E. Graham. 1996. Metabolic, catecholamine, and endurance responses to caffeine during intense exercise. Journal of Applied Physiology 81:1658–63. doi:10.1152/jappl.1996.81.4.1658.
  • Jacobson, B. H., M. D. Weber, L. Claypool, and L. E. Hunt. 1992. Effect of caffeine on maximal strength and power in élite male athletes. British Journal of Sports Medicine 26:276–80. doi:10.1136/bjsm.26.4.276.
  • Jahanfar, S., and S. H. Jaafar. 2013. Effects of restricted caffeine intake by mother on fetal, neonatal and pregnancy outcome. Cochrane Database of Systematic Reviews 2:CD006965.
  • Jahanfar, S., and S. H. Jaafar. 2015. Effects of restricted caffeine intake by mother on fetal, neonatal and pregnancy outcomes. Cochrane Database of Systematic Reviews 6:CD006965.
  • Jha, M. N., J. R. Bamburg, B. W. Bernstein, and J. S. Bedford. 2002. Caffeine eliminates gamma-ray-induced G2-phase delay in human tumor cells but not in normal cells. Radiation Research 157:26–31. doi:10.1667/0033-7587(2002)157%5b0026:CEGRIG%5d2.0.CO;2.
  • Jiang, X., L. Lim, J. Daly, A. Li, K. Jacobson, and M. Roberge. 2000. Structure-activity relationships for G2 checkpoint inhibition by caffeine analogs. International Journal of Oncology. 16.
  • Jiao, H., G. Hu, D. Gu, and X. Ni. 2015. Having a promising efficacy on Type II Diabetes, it's definitely a green tea time. Current Medicinal Chemistry 22:70–79. doi:10.2174/0929867321666140815123645.
  • Joghataie, M. T., M. Roghani, F. Negahdar, and L. Hashemi. 2004. Protective effect of caffeine against neurodegeneration in a model of Parkinson's disease in rat: behavioral and histochemical evidence. Parkinsonism & related disorders 10:465–68. doi:10.1016/j.parkreldis.2004.06.004.
  • Johnson-Kozlow, M., D. Kritz-Silverstein, E. Barrett-Connor, and D. Morton. 2002. Coffee consumption and cognitive function among older adults. American Journal of Epidemiology 156:842–50. doi:10.1093/aje/kwf119.
  • Kakuyama, A., and Y. Sadzuka. 2001. Effect of methylxanthine derivatives on doxorubicin transport and antitumor activity. Current Drug Metabolism 2:379–95. doi:10.2174/1389200013338270.
  • Kalaria, R. N. 1992. The blood-brain barrier and cerebral microcirculation in Alzheimer disease. Cerebrovascular and Brain Metabolism Reviews 4:226–60.
  • Kalaria, R. N. 1999. The blood-brain barrier and cerebrovascular pathology in Alzheimer's disease. Annals of the New York Academy of Sciences 893:113–25. doi:10.1111/j.1749-6632.1999.tb07821.x.
  • Kalaria, R. N., S. Sromek, B. J. Wilcox, and J. R. Unnerstall. 1990. Hippocampal adenosine A1 receptors are decreased in Alzheimer's disease. Neuroscience Letters 118:257–60. doi:10.1016/0304-3940(90)90641-L.
  • Kaplan, G. B., D. J. Greenblatt, B. L. Ehrenberg, J. E. Goddard, M. M. Cotreau, J. S. Harmatz, and R. I. Shader. 1997. Dose-dependent pharmacokinetics and psychomotor effects of caffeine in humans. The Journal of Clinical Pharmacology 37:693–703. doi:10.1002/j.1552-4604.1997.tb04356.x.
  • Kawabe, T. 2004. G2 checkpoint abrogators as anticancer drugs. Molecular Cancer Therapeutics 3:513–19.
  • Kawahara, M., Y. Takashi, K. Takazawa, H. Tsuchiya, K. Tomita, K. Yokogawa, and K.-I. Miyamoto. 2008. Caffeine dose-dependently potentiates the antitumor effect of cisplatin on osteosarcomas. Anticancer Research 28:1681–85.
  • Kawai, A., Y. Okada, K. Mückenhoff, and P. Scheid. 1995. Theophylline and hypoxic ventilatory response in the rat isolated brainstem-spinal cord. Respiration Physiology 100:25–32. doi:10.1016/0034-5687(94)00124-I.
  • Keijzers, G. B., B. E. De Galan, C. J. Tack, and P. Smits. 2002. Caffeine can decrease insulin sensitivity in humans. Diabetes Care 25:364–69. doi:10.2337/diacare.25.2.364.
  • Kelleher, D. K., O. Thews, and P. Vaupel. 1998. Regional perfusion and oxygenation of tumors upon methylxanthine derivative administration. International Journal of Radiation Oncology 42:861–64. doi:10.1016/S0360-3016(98)00318-6.
  • Khan, N., M. Monagas, C. Andres-Lacueva, R. Casas, M. Urpí-Sardà, R. M. Lamuela-Raventós, and R. Estruch. 2012. Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascular disease. Nutrition, Metabolism and Cardiovascular Diseases 22:1046–53. doi:10.1016/j.numecd.2011.02.001.
  • Kim, T.-W., Y.-O. Shin, J.-B. Lee, Y.-K. Min, and H.-M. Yang. 2010. Effect of caffeine on the metabolic responses of lipolysis and activated sweat gland density in human during physical activity. Food Science and Biotechnology 19:1077–81. doi:10.1007/s10068-010-0151-6.
  • Kimura, H., H. Tsuchiya, T. Shirai, H. Nishida, K. Hayashi, A. Takeuchi, I. Ohnari, and K. Tomita. 2009. Caffeine-potentiated chemotherapy for metastatic osteosarcoma. Journal of Orthopaedic Science 14:556–65. doi:10.1007/s00776-009-1372-5.
  • Knight, R. J., C. J. Bowmer, and M. S. Yates. 1993. The diuretic action of 8-cyclopentyl-1,3-dipropylxanthine, a selective A1 adenosine receptor antagonist. British Journal of Pharmacology 109:271–77. doi:10.1111/j.1476-5381.1993.tb13564.x.
  • Kong, H., P. P. Jones, A. Koop, L. Zhang, H. J. Duff, and S. R. Wayne Chen. 2008. Caffeine induces Ca(2+) release by reducing the threshold for luminal Ca(2+) activation of the ryanodine receptor. The Biochemical journal 414:441–52. doi:10.1042/BJ20080489.
  • Kopf, G. S., C. A. Lewis, and V. D. Vacquier. 1984. Characterization of basal and methylxanthine-stimulated Ca2+ transport in abalone spermatozoa. Journal of Biological Chemistry 259:5514–20.
  • Korematsu, S., H. Miyahara, T. Nagakura, S. Suenobu, and T. Izumi. 2008. Theophylline-associated seizures and their clinical characterizations. Pediatrics International 50:95–98. doi:10.1111/j.1442-200X.2007.02524.x.
  • Kortekaas, R., K. L. Leenders, J. C. H. van Oostrom, W. Vaalburg, J. Bart, A. T. M. Willemsen, and N. H. Hendrikse. 2005. Blood–brain barrier dysfunction in parkinsonian midbrain in vivo. Annals of Neurology 57:176–79. doi:10.1002/ana.20369.
  • Kot, M., and W. A. Daniel. 2008. The relative contribution of human cytochrome P450 isoforms to the four caffeine oxidation pathways: An in vitro comparative study with cDNA-expressed P450s including CYP2C isoforms. Biochemical Pharmacology 76:543–51. doi:10.1016/j.bcp.2008.05.025.
  • Kovacs, E. M. R., M. P. G. M. Lejeune, I. Nijs, and M. S. Westerterp-Plantenga. 2004. Effects of green tea on weight maintenance after body-weight loss. British Journal of Nutrition 91:431–37. doi:10.1079/BJN20041061.
  • Kovacs, E. M. R., J. H. C. H. Stegen, and F. Brouns. 1998. Effect of caffeinated drinks on substrate metabolism, caffeine excretion, and performance. Journal of Applied Physiology 85:709–15. doi:10.1152/jappl.1998.85.2.709.
  • Kretschmar, J. A., and T. W. Baumann. 1999. Caffeine in Citrus flowers. Phytochemistry 52:19–23. doi:10.1016/S0031-9422(99)00119-3.
  • Kris-Etherton, P. M., J. A. Derr, V. A. Mustad, F. H. Seligson, and T. A. Pearson. 1994. Effects of a milk chocolate bar per day substituted for a high-carbohydrate snack in young men on an NCEP/AHA Step 1 Diet. The American Journal of Clinical Nutrition 60:1037S–42S. doi:10.1093/ajcn/60.6.1037S.
  • Krul, C., and G. Hageman. 1998. Analysis of urinary caffeine metabolites to assess biotransformation enzyme activities by reversed-phase high-performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications 709:27–34. doi:10.1016/S0378-4347(98)00016-4.
  • Kuczkowski, K. M. 2009. Caffeine in pregnancy. Archives of Gynecology and Obstetrics 280:695–98. doi:10.1007/s00404-009-0991-6.
  • Kuemmerle, J. F., K. S. Murthy, and G. M. Makhlouf. 1994. Agonist-activated, ryanodine-sensitive, IP3-insensitive Ca2+ release channels in longitudinal muscle of intestine. American Journal of Physiology – Cell Physiology 266:C1421–31. doi:10.1152/ajpcell.1994.266.5.C1421.
  • Kuo, J. F., and E. C. De Renzo. 1969. A comparison of the effects of lipolytic and antilipolytic agents on adenosine 3′,5′-monophosphate levels in adipose cells as determined by prior labeling with adenine-8-14C. The Journal of Biological Chemistry 244:2252–60.
  • Lachance, M. P. 1982. The pharmacology and toxicology of caffeine. Journal of Food Safety 4:71–112. doi:10.1111/j.1745-4565.1982.tb00435.x.
  • Lagercrantz, H., Y. Yamamoto, B. B. Fredholm, N. R. Prabhakar, and C. von Euler. 1984. Adenosine analogues depress ventilation in rabbit neonates. Theophylline stimulation of respiration via adenosine receptors? Pediatric Research 18:387–90.
  • Laitala, V. S., J. Kaprio, M. Koskenvuo, I. Räihä, J. O. Rinne, and K. Silventoinen. 2009. Coffee drinking in middle age is not associated with cognitive performance in old age. The American Journal of Clinical Nutrition 90:640–46. doi:10.3945/ajcn.2009.27660.
  • Lam, A., and M. T. Newhouse. 1990. Management of asthma and chronic airflow limitation: Are methylxanthines obsolete?. Chest 98:44–52. doi:10.1378/chest.98.1.44.
  • Larsson, S. C., and N. Orsini. 2011. Coffee consumption and risk of stroke: A dose-response meta-analysis of prospective studies. American Journal of Epidemiology 174:993–1001. doi:10.1093/aje/kwr226.
  • Laska, E. M., A. Sunshine, F. Mueller, W. B. Elvers, C. Siegel, and A. Rubin. 1984. Caffeine as an analgesic adjuvant. JAMA 251:1711–18. doi:10.1001/jama.1984.03340370043028.
  • Lee, I.-A., A. Kamba, D. Low, and E. Mizoguchi. 2014. Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease. World Journal of Gastroenterology: WJG 20:1127–38. doi:10.3748/wjg.v20.i5.1127.
  • Lelo, A., D. J. Birkett, R. A. Robson, and J. O. Miners. 1986. Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. British Journal of Clinical Pharmacology 22:177–82. doi:10.1111/j.1365-2125.1986.tb05246.x.
  • León-Carmona, J. R., and A. Galano. 2011. Is caffeine a good scavenger of oxygenated free radicals? The Journal of Physical Chemistry B 115:4538–46. doi:10.1021/jp201383y.
  • Li, W., S. Dai, J. An, P. Li, X. Chen, R. Xiong, P. Liu, H. Wang, Y. Zhao, M. Zhu, X. Liu, P. Zhu, J. F. Chen, and Y. Zhou. 2008. Chronic but not acute treatment with caffeine attenuates traumatic brain injury in the mouse cortical impact model. Neuroscience 151:1198–207. doi:10.1016/j.neuroscience.2007.11.020.
  • Liao, S. 2001. The medicinal action of androgens and green tea epigallocatechin gallate. Hong Kong Medical Journal 7:369–74.
  • Lieberman, H. R. 2001. The effects of ginseng, ephedrine, and caffeine on cognitive performance, mood and energy. Nutrition Reviews 59:91–102. doi:10.1111/j.1753-4887.2001.tb06995.x.
  • Lindsay, J., D. Laurin, R. Verreault, R. Hébert, B. Helliwell, G. B. Hill, and I. McDowell. 2002. Risk factors for Alzheimer's disease: A prospective analysis from the Canadian Study of Health and Aging. American Journal of Epidemiology 156:445–53. doi:10.1093/aje/kwf074.
  • Liu, W., and G. Meissner. 1997. Structure-activity relationship of xanthines and skeletal muscle ryanodine receptor/Ca2+ release channel. Pharmacology 54:135–43. doi:10.1159/000139480.
  • Lopez-Garcia, E., R. M. van Dam, S. Rajpathak, W. C. Willett, J. E. Manson, and F. B. Hu. 2006. Changes in caffeine intake and long-term weight change in men and women. The American Journal of Clinical Nutrition 83:674–80. doi:10.1093/ajcn.83.3.674.
  • Lopez, F., L. G. Miller, D. J. Greenblatt, G. B. Kaplan, and R. I. Shader. 1989. Interaction of caffeine with the GABAA receptor complex: alterations in receptor function but not ligand binding. European Journal of Pharmacology: Molecular Pharmacology 172:453–59. doi:10.1016/0922-4106(89)90028-X.
  • Lorist, M. M., and M. Tops. 2003. Caffeine, fatigue, and cognition. Brain and Cognition 53:82–94. doi:10.1016/S0278-2626(03)00206-9.
  • Lovallo, W. R., M. F. Wilson, A. S. Vincent, B. H. Sung, B. S. McKey, and T. L. Whitsett. 2004. Blood pressure response to caffeine shows incomplete tolerance after short-term regular consumption. Hypertension 43:760–65. doi:10.1161/01.HYP.0000120965.63962.93.
  • Lozano, R. P., Y. A. García, D. B. Tafalla, and M. F. Albaladejo. 2007. Cafeína: un nutriente, un fármaco, o una droga de abuso. Addicciones 19:225–38.
  • Lu, G., J. Liao, G. Yang, K. R. Reuhl, X. Hao, and C. S. Yang. 2006b. Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone–induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine. Cancer Research 66:11494–501. doi:10.1158/0008-5472.CAN-06-1497.
  • Lu, Y.-P., Y.-R. Lou, J.-G. Xie, Q.-Y. Peng, J. Liao, C. S. Yang, M.-T. Huang, and A. H. Conney. 2002. Topical applications of caffeine or (−)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proceedings of the National Academy of Sciences of the United States of America 99:12455–60. doi:10.1073/pnas.182429899.
  • Lu, Y.-P., Y.-R. Lou, J.-G. Xie, Q.-Y. Peng, S. Zhou, Y. Lin, W. J. Shih, and A. H. Conney. 2006a. Caffeine and caffeine sodium benzoate have a sunscreen effect, enhance UVB-induced apoptosis, and inhibit UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis 28:199–206. doi:10.1093/carcin/bgl112.
  • Maemoto, T., M. Tada, T. Mihara, N. Ueyama, H. Matsuoka, K. Harada, T. Yamaji, K. Shirakawa, S. Kuroda, A. Akahane, A. Iwashita, N. Matsuoka, and S. Mutoh. 2004. Pharmacological characterization of FR194921, a new potent, selective, and orally active antagonist for central adenosine A1 receptors. Journal of Pharmacological Sciences 96:42–52. doi:10.1254/jphs.FP0040359.
  • Maia, L., and A. de Mendonça. 2002. Does caffeine intake protect from Alzheimer's disease? European Journal of Neurology 9:377–82. doi:10.1046/j.1468-1331.2002.00421.x.
  • Makower, D., U. Malik, Y. Novik, and P. H. Wiernik. 1999. Therapeutic efficacy of theophylline in chronic lymphocytic leukemia. Medical Oncology 16:69–71. doi:10.1007/BF02787362.
  • Malki, A. M., J. Gentry, and S. C. Evans. 2006. Differential effect of selected methylxanthine derivatives on radiosensitization of lung carcinoma cells. Experimental Oncology 28:16–24.
  • Marangos, P. J., S. M. Paul, A. M. Parma, F. K. Goodwin, P. Syapin, and P. Skolnick. 1979. Purinergic inhibition of diazepam binding to rat brain (in vitro). Life Sciences 24:851–57. doi:10.1016/0024-3205(79)90369-2.
  • Mariot, P., N. Prevarskaya, M. M. Roudbaraki, X. Le Bourhis, F. Van Coppenolle, K. Vanoverberghe, and R. Skryma. 2000. Evidence of functional ryanodine receptor involved in apoptosis of prostate cancer (LNCaP) cells. The Prostate 43:205–14. doi:10.1002/(SICI)1097-0045(20000515)43:3%3c205::AID-PROS6%3e3.0.CO;2-M.
  • Martínez-López, S., B. Sarriá, G. Baeza, R. Mateos, and L. Bravo-Clemente. 2014. Pharmacokinetics of caffeine and its metabolites in plasma and urine after consuming a soluble green/roasted coffee blend by healthy subjects. Food Research International 64:125–33. doi:10.1016/j.foodres.2014.05.043.
  • Martínez-Pinilla, E., A. Oñatibia-Astibia, and R. Franco. 2015. The relevance of theobromine for the beneficial effects of cocoa consumption. Frontiers in Pharmacology 6:1–5.
  • Martins, A. D., M. G. Alves, R. L. Bernardino, T. R. Dias, B. M. Silva, and P. F. Oliveira. 2013. Effect of white tea (Camellia sinensis (L.)) extract in the glycolytic profile of Sertoli cell. European Journal of Nutrition 53:1383–91. doi:10.1007/s00394-013-0640-5.
  • Matsui, T. 2015. Condensed catechins and their potential health-benefits. European Journal of Pharmacology 765:495–502. doi:10.1016/j.ejphar.2015.09.017.
  • Maughan, R. J., and J. Griffin. 2003. Caffeine ingestion and fluid balance: a review. Journal of Human Nutrition and Dietetics 16:411–20. doi:10.1046/j.1365-277X.2003.00477.x.
  • Mazzafera, P., and A. Carvalho. 1991. Breeding for low seed caffeine content of coffee (Coffea L.) by interspecific hybridization. Euphytica 59:55–60.
  • McPherson, P. S., Y.-K. Kim, H. Valdivia, C. M. Knudson, H. Takekura, C. Franzini-Armstrong, R. Coronadot, and K. P. Campbell. 1991. The brain ryanodine receptor: A caffeine-sensitive calcium release channel. Neuron 7:17–25. doi:10.1016/0896-6273(91)90070-G.
  • Mellor, D. D., T. Sathyapalan, E. S. Kilpatrick, S. Beckett, and S. L. Atkin. 2010. High-cocoa polyphenol-rich chocolate improves HDL cholesterol in Type 2 diabetes patients. Diabetic Medicine 27:1318–21. doi:10.1111/j.1464-5491.2010.03108.x.
  • Merighi, S., A. Benini, P. Mirandola, S. Gessi, K. Varani, C. Simioni, E. Leung, S. Maclennan, P. G. Baraldi, and P. A. Borea. 2007. Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1α, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells. Molecular Pharmacology 72:395–406. doi:10.1124/mol.106.032920.
  • Minton, N., and J. Henry. 1996. Acute and chronic human toxicity of theophylline. Human & Experimental Toxicology 15:471–81. doi:10.1177/096032719601500603.
  • Mioranzza, S., M. S. Costa, P. H. S. Botton, A. P. Ardais, V. L. Matte, J. Espinosa, D. O. Souza, and L. O. Porciúncula. 2011. Blockade of adenosine A1 receptors prevents methylphenidate-induced impairment of object recognition task in adult mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35:169–76. doi:10.1016/j.pnpbp.2010.10.022.
  • Mitchell, E. S., M. Slettenaar, N. vd Meer, C. Transler, L. Jans, F. Quadt, and M. Berry. 2011. Differential contributions of theobromine and caffeine on mood, psychomotor performance and blood pressure. Physiology & Behavior 104:816–22. doi:10.1016/j.physbeh.2011.07.027.
  • Miwa, S., S. Kitamura, T. Shirai, K. Hayashi, H. Nishida, A. Takeuchi, T. Nojima, and H. Tsuchiya. 2010. Desmoplastic small round cell tumour successfully treated with caffeine-assisted chemotherapy: A case report and review of the literature. Anticancer Research 30:3769–74.
  • Mongraw-Chaffin, M. L., B. A. Cohn, R. D. Cohen, and R. E. Christianson. 2008. Maternal smoking, alcohol consumption, and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: A prospective study in the child health and development studies cohort, 1959–1967. American Journal of Epidemiology 167. doi:10.1093/aje/kwm311.
  • Monteiro, J., M. Alves, P. Oliveira, and B. Silva. 2016. Structure-bioactivity relationships of methylxanthines: Trying to make sense of all the promises and the drawbacks. Molecules 21:974. doi:10.3390/molecules21080974.
  • Morelli, M., A. R. Carta, and P. Jenner. 2009. Adenosine A2A receptors and Parkinson's disease. In Adenosine receptors in health and disease, ed. N. C. Wilson, and J. S. Mustafa, 589–615. Berlin: Springer Berlin Heidelberg.
  • Morimoto, C., K. Kameda, T. Tsujita, and H. Okuda. 2001. Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells. Journal of Lipid Research 42:120–27.
  • Mosca, E. V., P. Ciechanski, A. Roy, E. C. Scheibli, K. Ballanyi, and R. J. A. Wilson. 2014. Methylxanthine reversal of opioid-induced respiratory depression in the neonatal rat: Mechanism and location of action. Respiratory Physiology & Neurobiology 200:80–89. doi:10.1016/j.resp.2014.06.002.
  • Mostofsky, E., G. Schlaug, K. J. Mukamal, W. D. Rosamond, and M. A. Mittleman. 2010. Coffee and acute ischemic stroke onset: The Stroke Onset Study. Neurology 75:1583–88. doi:10.1212/WNL.0b013e3181fb443d.
  • Mueni, E., N. Opiyo, and M. English. 2009. Caffeine for the management of apnea in preterm infants. International health 1:190–95. doi:10.1016/j.inhe.2009.09.005.
  • Muley, A., P. Muley, and M. Shah. 2012. Coffee to reduce risk of type 2 diabetes?: A systematic review. Current Diabetes Reviews 8:162–68. doi:10.2174/157339912800564016.
  • Müller, C. E., and J. W. Daly. 1993. Stimulation of calcium release by caffeine analogs in pheochromocytoma cells. Biochemical Pharmacology 46:1825–29. doi:10.1016/0006-2952(93)90589-O.
  • Mumford, K. G., L. N. Benowitz, M. S. Evans, J. B. Kaminski, L. K. Preston, A. C. Sannerud, K. Silverman, and R. R. Griffiths. 1996. Absorption rate of methylxanthines following capsules, cola and chocolate. European Journal of Clinical Pharmacology 51:319–25. doi:10.1007/s002280050205.
  • Mursu, J., S. Voutilainen, T. Nurmi, T. H. Rissanen, J. K. Virtanen, J. Kaikkonen, K. Nyyssönen, and J. T. Salonen. 2004. Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans. Free Radical Biology and Medicine 37:1351–59. doi:10.1016/j.freeradbiomed.2004.06.002.
  • Nathanson, J. 1984. Caffeine and related methylxanthines: possible naturally occurring pesticides. Science 226:184–87. doi:10.1126/science.6207592.
  • Nawrot, P., S. Jordan, J. Eastwood, J. Rotstein, A. Hugenholtz, and M. Feeley. 2003. Effects of caffeine on human health. Food Additives and Contaminants 20:1–30. doi:10.1080/0265203021000007840.
  • Nehlig, A. 1999. Are we dependent upon coffee and caffeine? A review on human and animal data. Neuroscience & Biobehavioral Reviews 23:563–76. doi:10.1016/S0149-7634(98)00050-5.
  • Nehlig, A. 2004. Dependence upon coffee and caffeine: an update. In Coffee, tea, chocolate, and the brain, A., N. ( Ed.), 133–46. Boca Raton: CRC Press.
  • Nehlig, A. 2010a. Is caffeine a cognitive enhancer?. Journal of Alzheimers Disease: JAD 20:S85–94. doi:10.3233/JAD-2010-091315.
  • Nehlig, A. 2015. Effects of coffee/caffeine on brain health and disease: What should I tell my patients?. Practical Neurology 0:1–7.
  • Nehlig, A., J.-P. Armspach, and I. J. Namer. 2010b. SPECT assessment of brain activation induced by caffeine: no effect on areas involved in dependence. Dialogues in Clinical Neuroscience 12:255–63.
  • Neufingerl, N., Y. E. Zebregs, E. A. Schuring, and E. A. Trautwein. 2013. Effect of cocoa and theobromine consumption on serum HDL-cholesterol concentrations: a randomized controlled trial. The American Journal of Clinical Nutrition 97:1201–1209. doi:10.3945/ajcn.112.047373.
  • Newton, R., L. J. Broughton, M. J. Lind, P. J. Morrison, H. J. Rogers, and I. D. Bradbrook. 1981a. Plasma and salivary pharmacokinetics of caffeine in man. European Journal of Clinical Pharmacology 21:45–52. doi:10.1007/BF00609587.
  • Newton, R., L. J. Broughton, M. J. Lind, P. J. Morrison, H. J. Rogers, and I. D. Bradbrook. 1981b. Plasma and salivary pharmacokinetics of caffeine in man. European Journal of Clinical Pharmacololoy 21:45–52. doi:10.1007/BF00609587.
  • Nguyen, D. T., and R. R. Walters. 2014. Standardizing management of post-dural puncture headache in obstetric patients: A literature review. Open Journal of Anesthesiolog:244–53. doi:10.4236/ojanes.2014.410037.
  • Nicholson, C. D., S. A. Jackman, and R. Wilke. 1989. The ability of denbufylline to inhibit cyclic nucleotide phosphodiesterase and its affinity for adenosine receptors and the adenosine re-uptake site. British Journal of Pharmacology 97:889–97. doi:10.1111/j.1476-5381.1989.tb12029.x.
  • Nunes, A. R., M. G. Alves, P. I. Moreira, P. F. Oliveira, and B. M. Silva. 2014. Can tea consumption be a safe and effective therapy against Diabetes Mellitus-induced neurodegeneration?. Current Neuropharmacology 12:475–89. doi:10.2174/1570159X13666141204220539.
  • Nunes, A. R., M. G. Alves, G. D. Tomás, V. R. Conde, A. C. Cristóvão, P. I. Moreira, P. F. Oliveira, and B. M. Silva. 2015. Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats. British Journal of Nutrition 113:832–42. doi:10.1017/S0007114514004395.
  • Ogilvie, R. I. 1978. Clinical pharmacokinetics of theophylline. Clinical Pharmacokinetics 3:267–93. doi:10.2165/00003088-197803040-00002.
  • Okazaki, H., J.-i. Osuga, Y. Tamura, N. Yahagi, S. Tomita, F. Shionoiri, Y. Iizuka, K. Ohashi, K. Harada, S. Kimura, T. Gotoda, H. Shimano, N. Yamada, and S. Ishibashi. 2002. Lipolysis in the absence of hormone-sensitive lipase: Evidence for a common mechanism regulating distinct lipases. Diabetes 51:3368–75. doi:10.2337/diabetes.51.12.3368.
  • Okuno, T., T. Sugiyama, M. Tominaga, S. Kojima, and T. Ikeda. 2002. Effects of caffeine on microcirculation of the human ocular fundus. Japanese Journal of Ophthalmology 46:170–76. doi:10.1016/S0021-5155(01)00498-1.
  • Oleaga, C., M. García, A. Solé, C. J. Ciudad, M. Izquierdo-Pulido, and V. Noé. 2011. CYP1A1 is overexpressed upon incubation of breast cancer cells with a polyphenolic cocoa extract. European Journal of Nutrition 51:465–76. doi:10.1007/s00394-011-0231-2.
  • Oliveira, P. F., G. D. Tomás, T. R. Dias, A. D. Martins, L. Rato, M. G. Alves, and B. M. Silva. 2015. White tea consumption restores sperm quality in prediabetic rats preventing testicular oxidative damage. Reproductive BioMedicine Online 31:544–56. doi:10.1016/j.rbmo.2015.06.021.
  • Olson, K. R., N. L. Benowitz, O. Woo, and S. M. Pond. 1985. Theophylline overdose: Acute single ingestion versus chronic repeated overmedication. Journal of Emergency Medicine 3:498. doi:10.1016/0736-4679(85)90019-8.
  • Orrú, M., X. Guitart, M. Karcz-Kubicha, M. Solinas, Z. Justinova, S. K. Barodia, J. Zanoveli, A. Cortes, C. Lluis, V. Casado, F. G. Moeller, and S. Ferré. 2013. Psychostimulant pharmacological profile of paraxanthine, the main metabolite of caffeine in humans. Neuropharmacology 67C:476–84. doi:10.1016/j.neuropharm.2012.11.029.
  • Osswald, H., and J. Schnermann. 2011. Methylxanthines and the kidney. Handbook of Experimental Pharmacology 200:391–412. doi:10.1007/978-3-642-13443-2_15.
  • Palacios, N., X. Gao, M. L. McCullough, M. A. Schwarzschild, R. Shah, S. Gapstur, and A. Ascherio. 2012. Caffeine and risk of Parkinson disease in a large cohort of men and women. Movement disorders: official journal of the Movement Disorder Society 27:1276–82. doi:10.1002/mds.25076.
  • Papadimitriou, A., K. C. Silva, E. B. M. I. Peixoto, C. M. Borges, J. M. Lopes de Faria, and J. B. Lopes de Faria. 2015. Theobromine increases NAD+/Sirt-1 activity and protects the kidney under diabetic conditions. American Journal of Physiology – Renal Physiology 308:F209–25. doi:10.1152/ajprenal.00252.2014.
  • Passmore, A. P., G. B. Kondowe, and G. D. Johnston. 1987. Renal and cardiovascular effects of caffeine: A dose–response study. Clinical Science 72:749–56. doi:10.1042/cs0720749.
  • Paynter, N. P., H.-C. Yeh, S. Voutilainen, M. I. Schmidt, G. Heiss, A. R. Folsom, F. L. Brancati, and W. H. L. Kao. 2006. Coffee and sweetened beverage consumption and the risk of type 2 diabetes mellitus: The atherosclerosis risk in communities study. American Journal of Epidemiology 164:1075–84. doi:10.1093/aje/kwj323.
  • Pendleton, M., S. Brown, C. Thomas, and B. Odle. 2012. Potential toxicity of caffeine when used as a dietary supplement for weight loss. Journal of Dietary Supplements 9:293–98. doi:10.3109/19390211.2012.736460.
  • Pendleton, M., S. Brown, C. M. Thomas, and B. Odle. 2013. Potential toxicity of caffeine when used as a dietary supplement for weight loss. Journal of Dietary Supplements 10:1–5. doi:10.3109/19390211.2012.758215.
  • Pereira, G. S., T. Mello e Souza, E. R. C. Vinadé, H. Choi, C. Rodrigues, A. M. O. Battastini, I. Izquierdo, J. J. F. Sarkis, and C. D. Bonan. 2002. Blockade of adenosine A1 receptors in the posterior cingulate cortex facilitates memory in rats. European Journal of Pharmacology 437:151–54. doi:10.1016/S0014-2999(02)01307-9.
  • Pereira, M. A., E. D. Parker, and A. R. Folsom. 2006. Coffee consumption and risk of type 2 diabetes mellitus: An 11-year prospective study of 28 812 postmenopausal women. Archives of Internal Medicine 166:1311–16. doi:10.1001/archinte.166.12.1311.
  • Perera, V., A. S. Gross, and A. J. McLachlan. 2010. Caffeine and paraxanthine HPLC assay for CYP1A2 phenotype assessment using saliva and plasma. Biomedical Chromatography 24:1136–44. doi:10.1002/bmc.1419.
  • Petzer, A., A. Pienaar, and J. P. Petzer. 2013. The interactions of caffeine with monoamine oxidase. Life Sciences 93:283–87. doi:10.1016/j.lfs.2013.06.020.
  • Petzer, J. P., and A. Petzer. 2015. Caffeine as a lead compound for the design of therapeutic agents for the treatment of Parkinson's disease. Current Medicinal Chemistry 22:975–88. doi:10.2174/0929867322666141215160015.
  • Pianosi, P., D. Grondin, K. Desmond, A. L. Coates, and J. V. Aranda. 1994. Effect of caffeine on the ventilatory response to inhaled carbon dioxide. Respiration Physiology 95:311–20. doi:10.1016/0034-5687(94)90093-0.
  • Pollard, I., S. Williamson, and S. Magre. 1990. Influence of caffeine administered during pregnancy on the early differentiation of fetal rat ovaries and testes. Journal of Developmental Physiology 13:59–65.
  • Postuma, R. B., A. E. Lang, R. P. Munhoz, K. Charland, A. Pelletier, M. Moscovich, L. Filla, D. Zanatta, S. Rios Romenets, R. Altman, R. Chuang, and B. Shah. 2012. Caffeine for treatment of Parkinson disease: A randomized controlled trial. Neurology 79:651–58. doi:10.1212/WNL.0b013e318263570d.
  • Prasanthi, J. R. P., B. Dasari, G. Marwarha, T. Larson, X. Chen, J. D. Geiger, and O. Ghribi. 2010. Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet. Free radical biology & medicine 49:1212–20. doi:10.1016/j.freeradbiomed.2010.07.007.
  • Prediger, R. D. S., L. C. Batista, and R. N. Takahashi. 2005. Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats. Neurobiology of Aging 26:957–64. doi:10.1016/j.neurobiolaging.2004.08.012.
  • Printz, C. 2015. Regular coffee consumption may improve survival in patients with colon cancer. Cancer 121:4102–4103. doi:10.1002/cncr.28990.
  • Ptolemy, A. S., E. Tzioumis, A. Thomke, S. Rifai, and M. Kellogg. 2010. Quantification of theobromine and caffeine in saliva, plasma and urine via liquid chromatography–tandem mass spectrometry: A single analytical protocol applicable to cocoa intervention studies. Journal of Chromatography B 878:409–16. doi:10.1016/j.jchromb.2009.12.019.
  • Qi, H., and S. Li. 2014. Dose–response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease. Geriatrics & Gerontology International 14:430–39. doi:10.1111/ggi.12123.
  • Ragab, A., and K. N. Facharzt. 2014. Caffeine, Is it effective for prevention of postdural puncture headache in young adult patients? Egyptian Journal of Anaesthesia 30:181–86. doi:10.1016/j.egja.2013.11.005.
  • Rao, F. V., O. A. Andersen, K. A. Vora, J. A. DeMartino, and D. M. F. van Aalten. 2005. Methylxanthine drugs are chitinase inhibitors: Investigation of inhibition and binding modes. Chemistry & Biology 12:973–80. doi:10.1016/j.chembiol.2005.07.009.
  • Rengelshausen, J., H. Lindenmaier, T. Cihlar, I. Walter-Sack, W. E. Haefeli, and J. Weiss. 2004. Inhibition of the human organic anion transporter 1 by the caffeine metabolite 1-methylxanthine. Biochemical and Biophysical Research Communications 320:90–94. doi:10.1016/j.bbrc.2004.05.142.
  • Resman, B. H., H. P. Blumenthal, and W. J. Jusko. 1977. Breast milk distribution of theobromine from chocolate. The Journal of Pediatrics 91:477–80. doi:10.1016/S0022-3476(77)81329-2.
  • Ribeiro, J. A., and A. M. Sebastião. 2010. Caffeine and adenosine. Journal of Alzheimers Disease: JAD 20:S3–15. doi:10.3233/JAD-2010-1379.
  • Riedel, W., E. Hogervorst, R. Leboux, F. Verhey, H. van Praag, and J. Jolles. 1995. Caffeine attenuates scopolamine-induced memory impairment in humans. Psychopharmacology 122:158–68. doi:10.1007/BF02246090.
  • Rieg, T., H. Steigele, J. Schnermann, K. Richter, H. Osswald, and V. Vallon. 2005. Requirement of intact adenosine A1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine. Journal of Pharmacology and Experimental Therapeutics 313:403–409. doi:10.1124/jpet.104.080432.
  • Riesenhuber, A., M. Boehm, M. Posch, and C. Aufricht. 2006. Diuretic potential of energy drinks. Amino Acids 31:81–83. doi:10.1007/s00726-006-0363-5.
  • Riksen, N. P., P. Smits, and G. A. Rongen. 2011. The cardiovascular effects of methylxanthines. In Methylxanthines, 413–37. Berlin: Springer Berlin Heidelberg.
  • Ritchie, K., S. Artero, F. Portet, A. Brickman, J. Muraskin, E. Beaino, M.-L. Ancelin, and I. Carrière. 2010. Caffeine, cognitive functioning, and white matter lesions in the elderly: establishing causality from epidemiological evidence. Journal of Alzheimer's Disease 20 (Suppl 1):S161–66. doi:10.3233/JAD-2010-1387.
  • Ritchie, K., I. Carrière, A. de Mendonça, F. Portet, J. F. Dartigues, O. Rouaud, P. Barberger-Gateau, and M. L. Ancelin. 2007. The neuroprotective effects of caffeine: a prospective population study (the Three City Study). Neurology 69:536–45. doi:10.1212/01.wnl.0000266670.35219.0c.
  • Rivera-Oliver, M., and M. Díaz-Ríos. 2014a. Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: A review. Life Sciences 101:1–9. doi:10.1016/j.lfs.2014.01.083.
  • Rivera-Oliver, M., and M. Díaz-Ríos. 2014b. Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review. Life Sciences 101:1–9. doi:10.1016/j.lfs.2014.01.083.
  • Roca, D. J., G. D. Schiller, and D. H. Farb. 1988. Chronic caffeine or theophylline exposure reduces gamma-aminobutyric acid/benzodiazepine receptor site interactions. Molecular Pharmacology 33:481–85.
  • Rodopoulos, N., L. Höjvall, and A. Norman. 1996. Elimination of theobromine metabolites in healthy adults. Scandinavian Journal of Clinical and Laboratory Investigation 56:373–83. doi:10.3109/00365519609090590.
  • Rogers, P. J., C. Hohoff, S. V. Heatherley, E. L. Mullings, P. J. Maxfield, R. P. Evershed, J. Deckert, and D. J. Nutt. 2010. Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption. Neuropsychopharmacology 35:1973–83. doi:10.1038/npp.2010.71.
  • Roomi, M. W., V. Ivanov, T. Kalinovsky, A. Niedzwiecki, and M. Rath. 2006. Antitumor effect of ascorbic acid, lysine, proline, arginine, and green tea extract on bladder cancer cell line T-24. International Journal of Urology 13:415–19. doi:10.1111/j.1442-2042.2006.01309.x.
  • Rosenkranz, H. S., and F. K. Ennever. 1987. Evaluation of the genotoxicity of theobromine and caffeine. Food and Chemical Toxicology 25:247–51. doi:10.1016/0278-6915(87)90091-3.
  • Rosim, F. E., D. S. Persike, A. Nehlig, R. P. Amorim, D. M. de Oliveira, and M. J. d. S. Fernandes. 2011. Differential neuroprotection by A(1) receptor activation and A(2) receptor inhibition following pilocarpine-induced status epilepticus. Epilepsy & Behavior 22:207–13. doi:10.1016/j.yebeh.2011.07.004.
  • Ross, G., R. D. Abbott, H. Petrovitch, D. M. Morens, A. Grandinetti, K. H. Tung, C. M. Tanner, K. H. Masaki, P. L. Blanchette, J. D. Curb, J. S. Popper, and L. R. White. 2000a. Association of coffee and caffeine intake with the risk of parkinson disease. JAMA 283:2674–79. doi:10.1001/jama.283.20.2674.
  • Rousseau, E., J. Ladine, Q.-Y. Liu, and G. Meissner. 1988. Activation of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum by caffeine and related compounds. Archives of Biochemistry and Biophysics 267:75–86. doi:10.1016/0003-9861(88)90010-0.
  • Rovei, V., F. Chanoine, and M. Strolin Benedetti. 1982. Pharmacokinetics of theophylline: a dose-range study. British Journal of Clinical Pharmacology 14:769–78. doi:10.1111/j.1365-2125.1982.tb02035.x.
  • Ruangkittisakul, A., and K. Ballanyi. 2010. Methylxanthine reversal of opioid-evoked inspiratory depression via phosphodiesterase-4 blockade. Respiratory Physiology & Neurobiology 172:94–105. doi:10.1016/j.resp.2010.04.025.
  • Rudolphi, K. A., M. Keil, J. Fastbom, and B. B. Fredholm. 1989. Ischaemic damage in gerbil hippocampus is reduced following upregulation of adenosine (A1) receptors by caffeine treatment. Neuroscience Letters 103:275–80. doi:10.1016/0304-3940(89)90112-2.
  • Rush, J. W. E., and L. L. Spriet. 2001. Skeletal muscle glycogen phosphorylase akinetics: effects of adenine nucleotides and caffeine. Journal of Applied Physiology 91:2071–78. doi:10.1152/jappl.2001.91.5.2071.
  • Russo, C., G. Arcidiacono, and R. Polosa. 2006. Adenosine receptors: promising targets for the development of novel therapeutics and diagnostics for asthma. Fundamental & Clinical Pharmacology 20:9–19. doi:10.1111/j.1472-8206.2005.00388.x.
  • Ruxton, C. H. S. 2008. The impact of caffeine on mood, cognitive function, performance and hydration: a review of benefits and risks. Nutrition Bulletin 33:15–25. doi:10.1111/j.1467-3010.2007.00665.x.
  • Ryzhov, S., J. L. McCaleb, A. E. Goldstein, I. Biaggioni, and I. Feoktistov. 2007. Role of adenosine receptors in the regulation of angiogenic factors and neovascularization in hypoxia. Journal of Pharmacology and Experimental Therapeutics 320:565–72. doi:10.1124/jpet.106.114850.
  • Saaksjarvi, K., P. Knekt, H. Rissanen, M. A. Laaksonen, A. Reunanen, and S. Mannisto. 2007. Prospective study of coffee consumption and risk of Parkinson's disease. Eur J Clin Nutr 62:908–15. doi:10.1038/sj.ejcn.1602788.
  • Sabisz, M., and A. Skladanowski. 2008. Modulation of cellular response to anticancer treatment by caffeine: inhibition of cell cycle checkpoints, DNA repair and more. Current Pharmaceutical Biotechnology 9:325–36. doi:10.2174/138920108785161497.
  • Sadzuka, Y., E. Mochizuki, and Y. Takino. 1995. Mechanism of caffeine modulation of the antitumor activity of adriamycin. Toxicology Letters 75:39–49. doi:10.1016/0378-4274(94)03154-Y.
  • Salihović, M., S. Huseinović, S. Špirtović-Halilović, A. Osmanović, A. Dedić, Z. Ašimović, and D. Završnik. 2014. DFT study and biological activity of some methylxanthines. Bulletin of the Chemists and Technologists of Bosnia and Herzegovina 42:31–36.
  • Sankar, J., R. Lodha, and S. K. Kabra. 2008. Doxofylline: The next generation methylxanthine. Indian Journal of Pediatrics 75:251–54. doi:10.1007/s12098-008-0054-1.
  • Santos, C., N. Lunet, A. Azevedo, A. de Mendonça, K. Ritchie, and H. Barros. 2010. Caffeine intake is associated with a lower risk of cognitive decline: a cohort study from Portugal. Journal of Alzheimers Disease: JAD 20:S175–S1785. doi:10.3233/JAD-2010-091303.
  • Santos, J. R., and A. O. S. S. Rangel. 2012. Development of a chromatographic low pressure flow injection system: Application to the analysis of methylxanthines in coffee. Analytica Chimica Acta 715:57–63. doi:10.1016/j.aca.2011.12.002.
  • Sarkaria, J. N., E. C. Busby, R. S. Tibbetts, P. Roos, Y. Taya, L. M. Karnitz, and R. T. Abraham. 1999. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Research 59:4375–82.
  • Sarrazin, E., L. Hendeles, M. Weinberger, K. Muir, and S. Riegelman. 1980. Dose-dependent kinetics for theophylline: Observations among ambulatory asthmatic children. The Journal of Pediatrics 97:825–28. doi:10.1016/S0022-3476(80)80280-0.
  • Sarriá, B., S. Martínez-López, J. L. Sierra-Cinos, L. Garcia-Diz, L. Goya, R. Mateos, and L. Bravo. 2015. Effects of bioactive constituents in functional cocoa products on cardiovascular health in humans. Food Chemistry 174:214–18. doi:10.1016/j.foodchem.2014.11.004.
  • Sartorelli, D. S., G. Fagherazzi, B. Balkau, M. S. Touillaud, M.-C. Boutron-Ruault, B. de Lauzon-Guillain, and F. Clavel-Chapelon. 2010. Differential effects of coffee on the risk of type 2 diabetes according to meal consumption in a French cohort of women: the E3N/EPIC cohort study. The American Journal of Clinical Nutrition 91:1002–12. doi:10.3945/ajcn.2009.28741.
  • Satoh, H. 1993. Positive and negative chronotropic effects of caffeine in spontaneously beating rabbit sino-atrial node cells. General Pharmacology 24:1223–30. doi:10.1016/0306-3623(93)90372-5.
  • Scanlon, J. E., K. C. Chin, M. E. Morgan, G. M. Durbin, K. A. Hale, and S. S. Brown. 1992. Caffeine or theophylline for neonatal apnoea? Archives of Disease in Childhood 67:425–28. doi:10.1136/adc.67.4_Spec_No.425.
  • Schmidt, R. J., P. A. Romitti, T. L. Burns, M. L. Browne, C. M. Druschel, and R. S. Olney. 2009. Maternal caffeine consumption and risk of neural tube defects. Birth Defects Research Part A: Clinical and Molecular Teratology 85:879–89. doi:10.1002/bdra.20624.
  • Schoen, K., T. Yu, C. Stockmann, M. G. Spigarelli, and C. M. T. Sherwin. 2014. Use of methylxanthine therapies for the treatment and prevention of apnea of prematurity. Pediatric Drugs 16:169–77. doi:10.1007/s40272-013-0063-z.
  • Scholz, H. 1984. Inotropic drugs and their mechanisms of action. Journal of the American College of Cardiology 4:389–97. doi:10.1016/S0735-1097(84)80231-4.
  • Schuller, H. M., B. Porter, A. Riechert, K. Walker, and R. Schmoyer. 2004. Neuroendocrine lung carcinogenesis in hamsters is inhibited by green tea or theophylline while the development of adenocarcinomas is promoted: implications for chemoprevention in smokers. Lung Cancer 45:11–18. doi:10.1016/j.lungcan.2003.12.007.
  • Seale, T. W., T. H. Roderick, P. Johnson, L. Logan, O. M. Rennert, and J. M. Carney. 1986. Complex genetic determinants of susceptibility to methylxanthine-induced locomotor activity changes. Pharmacology Biochemistry and Behavior 24:1333–41. doi:10.1016/0091-3057(86)90193-0.
  • Seeram, N. P., S. M. Henning, Y. Niu, R. Lee, H. S. Scheuller, and D. Heber. 2006. Catechin and caffeine content of green tea dietary supplements and correlation with antioxidant capacity. Journal of Agricultural and Food Chemistry 54:1599–603. doi:10.1021/jf052857r.
  • Seino, S., H. Takahashi, W. Fujimoto, and T. Shibasaki. 2009. Roles of cAMP signalling in insulin granule exocytosis. Diabetes, Obesity and Metabolism 11:180–88. doi:10.1111/j.1463-1326.2009.01108.x.
  • Sessler, C. N. 1990. Theophylline toxicity: Clinical features of 116 consecutive cases. The American Journal of Medicine 88:567–76. doi:10.1016/0002-9343(90)90519-J.
  • Setchell, K. D. R., M. Beth Welsh, M. J. Klooster, W. F. Balistreri, and C. K. Lim. 1987. Rapid high-performance liquid chromatography assay for salivary and serum caffeine following an oral load. Journal of Chromatography A 385:267–74. doi:10.1016/S0021-9673(01)94639-4.
  • Shannon, M. 1993. Predictors of major toxicity after theophylline overdose. Annals of Internal Medicine 119:1161–67. doi:10.7326/0003-4819-119-12-199312150-00002.
  • Shannon, M., and F. H. Lovejoy. 1992. Effect of acute versus chronic intoxication on clinical features of theophylline poisoning in children. The Journal of Pediatrics 121:125–30. doi:10.1016/S0022-3476(05)82558-2.
  • Shi, D., W. L. Padgett, and J. W. Daly. 2003. Caffeine analogs: Effects on ryanodine-sensitive calcium-release channels and GABAA receptors. Cellular and Molecular Neurobiology 23:331–47. doi:10.1023/A:1023688604792.
  • Shively, C. A., S. M. Tarka, M. J. Arnaud, B. H. Dvorchik, G. Thomas Passananti, and E. S. Vesell. 1985. High levels of methylxanthines in chocolate do not alter theobromine disposition. Clinical Pharmacology & Therapeutics 37:415–24. doi:10.1038/clpt.1985.65.
  • Shou, Q., S. Pan, J. Tu, J. Jiang, Y. Ling, Y. Cai, M. Chen, and D. Wang. 2013. Modulation effect of Smilax glabra flavonoids on ryanodine receptor mediated intracellular Ca2+ release in cardiomyoblast cells. Journal of Ethnopharmacology 150:389–92. doi:10.1016/j.jep.2013.08.009.
  • Shukla, V., and R. P. Gude. 2003. Potentiation of lipid peroxidation in B16F10 and B16F1 melanoma cells by caffeine, a methylxanthine derivative: relationship to intracellular glutathione. Chemotherapy 49:71–75. doi:10.1159/000069785.
  • Simonin, C., C. Duru, J. Salleron, P. Hincker, P. Charles, A. Delval, K. Youssov, S. Burnouf, J.-P. Azulay, C. Verny, C. Scherer, C. Tranchant, C. Goizet, S. Debruxelles, L. Defebvre, B. Sablonnière, M. Romon-Rousseaux, L. Buée, A. Destée, O. Godefroy, A. Dürr, B. Landwehrmeyer, A.-C. Bachoud-Levi, F. Richard, D. Blum, and P. Krystkowiak. 2013. Association between caffeine intake and age at onset in Huntington's disease. Neurobiology of Disease 58:179–82. doi:10.1016/j.nbd.2013.05.013.
  • Simons, F. E. R., A. B. Becker, K. J. Simons, and C. A. Gillespie. 1985. The bronchodilator effect and pharmacokinetics of theobromine in young patients with asthma. Journal of Allergy and Clinical Immunology 76:703–707. doi:10.1016/0091-6749(85)90674-8.
  • Sinchai, T., S. Plasen, Y. Sanvarinda, Y. Jaisin, P. Govitrapong, N. P. Morales, P. Ratanachamnong, and D. Plasen. 2011. Caffeine potentiates methamphetamine-induced toxicity both in vitro and in vivo. Neuroscience Letters 502:65–69. doi:10.1016/j.neulet.2011.07.026.
  • Skopiński, P., M. Woronkowicz, E. Skopińska-Różewska, and A. Siwicki. 2011. The effects of prenatal exposure to methylxanthines. Polish Journal of Veterinary Sciences 14:695–701. doi:10.2478/v10181-011-0105-9.
  • Smit, H. J. 2011. Theobromine and the pharmacology of cocoa. In Methylxanthines, 201–34. Berlin: Springer Berlin Heidelberg.
  • Smit, H. J., E. A. Gaffan, and P. J. Rogers. 2004. Methylxanthines are the psycho-pharmacologically active constituents of chocolate. Psychopharmacology 176:412–19. doi:10.1007/s00213-004-1898-3.
  • Smith, I. F., B. Hitt, K. N. Green, S. Oddo, and F. M. LaFerla. 2005. Enhanced caffeine-induced Ca2+ release in the 3xTg-AD mouse model of Alzheimer's disease. Journal of Neurochemistry 94:1711–18. doi:10.1111/j.1471-4159.2005.03332.x.
  • Snyder, S. H., J. J. Katims, Z. Annau, R. F. Bruns, and J. W. Daly. 1981. Adenosine receptors and behavioral actions of methylxanthines. Proceedings of the National Academy of Sciences of the United States of America 78:3260–64. doi:10.1073/pnas.78.5.3260.
  • Soffietti, M. G., C. Nebbia, F. Valenza, S. Amedeo, and G. Re. 1989. Toxic effects of theobromine on mature and immature male rabbits. Journal of Comparative Pathology 100:47–58. doi:10.1016/0021-9975(89)90089-3.
  • Somani, S. M., N. N. Khanna, and H. S. Bada. 1980. Caffeine and theophylline: serum/CSF correlation in premature infants. The Journal of Pediatrics 96:1091–93. doi:10.1016/S0022-3476(80)80652-4.
  • Sonsalla, P. K., L.-Y. Wong, S. L. Harris, J. R. Richardson, I. Khobahy, W. Li, B. S. Gadad, and D. C. German. 2012. Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson's disease. Experimental Neurology 234:482–87. doi:10.1016/j.expneurol.2012.01.022.
  • Spriet, L. L., D. A. MacLean, D. J. Dyck, E. Hultman, G. Cederblad, and T. E. Graham. 1992. Caffeine ingestion and muscle metabolism during prolonged exercise in humans. American Journal of Physiology – Endocrinology and Metabolism 262:E891–98. doi:10.1152/ajpendo.1992.262.6.E891.
  • Srdjenovic, B., V. Djordjevic-Milic, N. Grujic, R. Injac, and Z. Lepojevic. 2008. Simultaneous HPLC determination of caffeine, theobromine, and theophylline in food, drinks, and herbal products. Journal of Chromatographic Science 46:144–49. doi:10.1093/chromsci/46.2.144.
  • Ståhle, L. 1991. Drug distribution studies with microdialysis: I. Tissue dependent difference in recovery between caffeine and theophylline. Life Sciences 49:1835–42. doi:10.1016/0024-3205(91)90486-U.
  • Stavric, B. 1988a. Methylxanthines: Toxicity to humans. 1. Theophylline. Food and Chemical Toxicology 26:541–65. doi:10.1016/0278-6915(88)90007-5.
  • Stavric, B. 1988b. Methylxanthines: Toxicity to humans. 2. Caffeine. Food and Chemical Toxicology 26:645–62. doi:10.1016/0278-6915(88)90236-0.
  • Stavric, B. 1988c. Methylxanthines: Toxicity to humans. 3. Theobromine, paraxanthine and the combined effects of methylxanthines. Food and Chemical Toxicology 26:725–33. doi:10.1016/0278-6915(88)90073-7.
  • Stolp, H. B., and K. M. Dziegielewska. 2009. Review: Role of developmental inflammation and blood–brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases. Neuropathology and Applied Neurobiology 35:132–46. doi:10.1111/j.1365-2990.2008.01005.x.
  • Sugawara, M., T. Mochizuki, Y. Takekuma, and K. Miyazaki. 2005. Structure–affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites. Biochimica et Biophysica Acta (BBA) – Biomembranes 1714:85–92. doi:10.1016/j.bbamem.2005.06.006.
  • Sugimoto, N., S. Miwa, Y. Hitomi, H. Nakamura, H. Tsuchiya, and A. Yachie. 2014. Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B. Nutrition and Cancer 66:419–23. doi:10.1080/01635581.2013.877497.
  • Sugimoto, T., M. Sugimoto, I. Uchida, T. Mashimo, and S. Okada. 2001. Inhibitory effect of theophylline on recombinant GABAA receptor. NeuroReport 12:489–93. doi:10.1097/00001756-200103050-00013.
  • Sugiura, C., S. Nishimatsu, T. Moriyama, S. Ozasa, T. Kawada, and K. Sayama. 2012. Catechins and caffeine inhibit fat accumulation in mice through the improvement of hepatic lipid metabolism. Journal of Obesity 2012:520510. doi:10.1155/2012/520510.
  • Takahashi, M., S. Yanoma, Y. Yamamoto, Y. Rino, T. Amano, and T. Imada. 1998. Combined effect of CDDP and caffeine against human gastric cell line in vivo. Anticancer Research 18:4399–401.
  • Takahashi, R. N., F. A. Pamplona, and R. D. Prediger. 2008. Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies. Frontiers in Bioscience: a journal and virtual library 13:2614–32. doi:10.2741/2870.
  • Takeda, M., S. Khamdang, S. Narikawa, H. Kimura, M. Hosoyamada, S. H. Cha, T. Sekine, and H. Endou. 2002a. Characterization of methotrexate transport and its drug interactions with human organic anion transporters. Journal of Pharmacology and Experimental Therapeutics 302:666–71. doi:10.1124/jpet.102.034330.
  • Takeda, M., S. Khamdang, S. Narikawa, H. Kimura, Y. Kobayashi, T. Yamamoto, S. H. Cha, T. Sekine, and H. Endou. 2002b. Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. Journal of Pharmacology and Experimental Therapeutics 300:918–24. doi:10.1124/jpet.300.3.918.
  • Talik, P., J. Krzek, and R. J. Ekiert. 2012. Analytical techniques used for determination of methylxanthines and their analogues—Recent advances. Separation & Purification Reviews 41:1–61. doi:10.1080/15422119.2011.569047.
  • Tarka, S. M., M. J. Arnaud, B. H. Dvorchik, and E. S. Vesell. 1983. Theobromine kinetics and metabolic disposition. Clinical Pharmacology & Therapeutics 34:546–55. doi:10.1038/clpt.1983.212.
  • Tarka, S. M., and H. H. Cornish. 1982. The toxicology of cocoa and methylxanthines: A review of the literature. CRC Critical Reviews in Toxicology 9:275–312. doi:10.3109/10408448209037495.
  • Tarka, S. M., B. L. Zoumas, and J. H. Gans. 1979. Short-term effects of graded levels of theobromine in laboratory rodents. Toxicology and Applied Pharmacology 49:127–49. doi:10.1016/0041-008X(79)90285-0.
  • Tash, J. S., and A. R. Means. 1982. Regulation of protein phosphorylation and motility of sperm by cyclic adenosine monophosphate and calcium. Biology of Reproduction 26:745–63. doi:10.1095/biolreprod26.4.745.
  • Tazzeo, T., G. Bates, H. N. Roman, A.-M. Lauzon, M. D. Khasnis, M. Eto, and L. J. Janssen. 2012. Caffeine relaxes smooth muscle through actin depolymerization. American Journal of Physiology – Lung Cellular and Molecular Physiology 303:L334–42. doi:10.1152/ajplung.00103.2012.
  • Teekachunhatean, S., N. Tosri, N. Rojanasthien, S. Srichairatanakool, and C. Sangdee. 2013. Pharmacokinetics of caffeine following a single administration of coffee enema versus oral coffee consumption in healthy male subjects. ISRN Pharmacology 2013:7. doi:10.1155/2013/147238.
  • Teunissen, M. W. E., I. O. N. Brorens, J. M. Geerlings, and D. D. Breimer. 1985. Dose-dependent elimination of theophylline in rats. Xenobiotica 15:165–71. doi:10.3109/00498258509045346.
  • Trincavelli, M. L., S. Daniele, and C. Martini. 2010. Adenosine receptors: what we know and what we are learning. Current Topics in Medicinal Chemistry 10:860–77. doi:10.2174/156802610791268756.
  • Tsai, J., T. L. Chern, S. C. Hu, C. H. Lee, R. B. Wang, and J. F. Deng. 1994. The clinical implication of theophylline intoxication in the Emergency Department. Human & Experimental Toxicology 13:651–57. doi:10.1177/096032719401301001.
  • Tsirilakis, K., C. Kim, A. G. Vicencio, C. Andrade, A. Casadevall, and D. L. Goldman. 2012. Methylxanthine inhibit fungal chitinases and exhibit antifungal activity. Mycopathologia 173:83–91. doi:10.1007/s11046-011-9483-x.
  • Tsuchiya, H., H. Yasutake, A. Yokogawa, H. Baba, Y. Ueda, and K. Tomita. 1992. Effect of chemotherapy combined with caffeine for osteosarcoma. Journal of Cancer Research and Clinical Oncology 118:567–69. doi:10.1007/BF01211797.
  • Uauy, R., D. L. Shapiro, B. Smith, and J. B. Warshaw. 1975. Treatment of severe apnea in prematures with orally administered theophylline. Pediatrics 55:595–98.
  • Ułas, J., L. C. Brunner, L. Nguyen, and C. W. Cotman. 1993. Reduced density of adenosine A1 receptors and preserved coupling of adenosine A1 receptors to G proteins in alzheimer hippocampus: A quantitative autoradiographic study. Neuroscience 52:843–54. doi:10.1016/0306-4522(93)90533-L.
  • Unachukwu, U. J., S. Ahmed, A. Kavalier, J. T. Lyles, and E. J. Kennelly. 2010. White and green teas (Camellia sinensisvar.sinensis): Variation in phenolic, methylxanthine, and antioxidant profiles. Journal of Food Science 75:C541–48. doi:10.1111/j.1750-3841.2010.01705.x.
  • Usmani, O. S., M. G. Belvisi, H. J. Patel, N. Crispino, M. A. Birrell, M. Korbonits, D. Korbonits, and P. J. Barnes. 2004. Theobromine inhibits sensory nerve activation and cough. The FASEB Journal 19(2):231–33.
  • van Boxtel, M. P. J., J. A. J. Schmitt, H. Bosma, and J. Jolles. 2003. The effects of habitual caffeine use on cognitive change: a longitudinal perspective. Pharmacology Biochemistry and Behavior 75:921–27. doi:10.1016/S0091-3057(03)00171-0.
  • van Buren, M., J. A. Bijlsma, P. Boer, H. J. van Rijn, and H. A. Koomans. 1993. Natriuretic and hypotensive effect of adenosine-1 blockade in essential hypertension. Hypertension 22:728–34. doi:10.1161/01.HYP.22.5.728.
  • van Dam, R. M., and E. J. M. Feskens. 2002. Coffee consumption and risk of type 2 diabetes mellitus. The Lancet 360:1477–78. doi:10.1016/S0140-6736(02)11436-X.
  • van Dam, R. M., and F. B. Hu. 2005. Coffee consumption and risk of type 2 diabetes: A systematic review. JAMA 294:97–104. doi:10.1001/jama.294.1.97.
  • van Dam, R. M., W. C. Willett, J. E. Manson, and F. B. Hu. 2006. Coffee, caffeine, and risk of type 2 diabetes: A prospective cohort study in younger and middle-aged U.S. women. Diabetes Care 29:398–403. doi:10.2337/diacare.29.02.06.dc05-1512.
  • Van der Walt, M. M., and G. Terre'Blanche. 2015. 1,3,7-Triethyl-substituted xanthines—possess nanomolar affinity for the adenosine A1 receptor. Bioorganic & Medicinal Chemistry 23:6641–49. doi:10.1016/j.bmc.2015.09.012.
  • van Gelder, B. M., B. Buijsse, M. Tijhuis, S. Kalmijn, S. Giampaoli, A. Nissinen, and D. Kromhout. 2006. Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study. Eur J Clin Nutr 61:226–32. doi:10.1038/sj.ejcn.1602495.
  • Van Soeren, M., T. Mohr, M. Kjaer, and T. E. Graham. 1996. Acute effects of caffeine ingestion at rest in humans with impaired epinephrine responses. Journal of Applied Physiology 80:999–1005. doi:10.1152/jappl.1996.80.3.999.
  • van Zyl, J. M., B. Derendinger, H. I. Seifart, and P. Van der Bijl. 2008. Comparative diffusion of drugs through bronchial tissue. International Journal of Pharmaceutics 357:32–36. doi:10.1016/j.ijpharm.2008.01.028.
  • Vercambre, M.-N., C. Berr, K. Ritchie, and J. H. Kang. 2013. Caffeine and cognitive decline in elderly women at high vascular risk. Journal of Alzheimer's disease: JAD 35(2):413–21. doi:10.3233/JAD-122371.
  • Vilela, V. R., A. L. de Oliveira, J. F. Comar, R. M. Peralta, and A. Bracht. 2014. Tadalafil inhibits the cAMP stimulated glucose output in the rat liver. Chemico-Biological Interactions 220:1–11. doi:10.1016/j.cbi.2014.05.020.
  • Wang, X., H. Wang, G. Iliakis, and Y. Wang. 2003. Caffeine-induced radiosensitization is independent of nonhomologous end joining of DNA double-strand breaks. Radiation Research 159:426–32. doi:10.1667/0033-7587(2003)159%5b0426:CIRIIO%5d2.0.CO;2.
  • Weckerle, C. S., M. A. Stutz, and T. W. Baumann. 2003. Purine alkaloids in Paullinia. Phytochemistry 64:735–42. doi:10.1016/S0031-9422(03)00372-8.
  • Weinberger, M., and E. Ginchansky. 1977. Dose-dependent kinetics of theophylline disposition in asthmatic children. Journal of Pediatrics 91:820–24. doi:10.1016/S0022-3476(77)81051-2.
  • Weinberger, M. A., L. Friedman, T. M. Farber, F. M. Moreland, E. L. Peters, C. E. Gilmore, and M. A. Khan. 1978. Testicular atrophy and impaired spermatogenesis in rats fed high levels of the methylxanthines caffeine, theobromine, or theophylline. Journal of Environmental Pathology and Toxicology 1:669–88.
  • Weng, X., R. Odouli, and D.-K. Li. 2008. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. American Journal of Obstetrics & Gynecology 198:279.e271–78. doi:10.1016/j.ajog.2007.10.803.
  • Wennergren, G., and M. Wennergren. 1983. Neonatal breathing control mediated via the central chemoreceptors. Acta Physiologica Scandinavica 119:139–46. doi:10.1111/j.1748-1716.1983.tb07319.x.
  • Westerterp-Plantenga, M. S., M. P. G. M. Lejeune, and E. M. R. Kovacs. 2005. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obesity Research 13:1195–204. doi:10.1038/oby.2005.142.
  • White, J. R., J. M. Padowski, Y. Zhong, G. Chen, S. Luo, P. Lazarus, M. E. Layton, and S. McPherson. 2016. Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Clinical Toxicology 54:308–12. doi:10.3109/15563650.2016.1146740.
  • Whitsett, T. L., C. V. Manion, and H. D. Christensen. 1984. Cardiovascular effects of coffee and caffeine. American Journal of Cardiology 53:918–22. doi:10.1016/0002-9149(84)90525-3.
  • Wilcox, A., C. Weinberg, and D. Baird. 1988. Caffeinated beverages and decreased fertility. The Lancet 332:1453–56. doi:10.1016/S0140-6736(88)90933-6.
  • Wilcox, C. S., W. J. Welch, G. F. Schreiner, and L. Belardinelli. 1999. Natriuretic and diuretic actions of a highly selective adenosine A1 receptor antagonist. Journal of the American Society of Nephrology 10:714–20.
  • Wilson, A. J., P. G. Gibson, and J. Coughlan. 2000. Long acting beta-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database of Systematic Reviews 2:CD001281.
  • Wostyn, P., D. Van Dam, K. Audenaert, and P. P. De Deyn. 2011. Increased cerebrospinal fluid production as a possible mechanism underlying caffeine's protective effect against Alzheimer's disease. International Journal of Alzheimer's Disease 2011:617420.
  • Xia, Z., Y. Ni, and S. Kokot. 2013. Simultaneous determination of caffeine, theophylline and theobromine in food samples by a kinetic spectrophotometric method. Food Chemistry 141:4087–93. doi:10.1016/j.foodchem.2013.06.121.
  • Yamaguchi, S., H. Funahashi, and T. Murakami. 2009. Improved fertility in gilts and sows after artificial insemination of frozen-thawed boar semen by supplementation of semen extender with caffeine and CaCl2. Journal of Reproduction and Development 55:645–49. doi:10.1262/jrd.20238.
  • Yang, H., J. Rouse, L. Lukes, M. Lancaster, T. Veenstra, M. Zhou, Y. Shi, Y.-G. Park, and K. Hunter. 2005. Caffeine suppresses metastasis in a transgenic mouse model: a prototype molecule for prophylaxis of metastasis. Clinical & Experimental Metastasis 21:719–35. doi:10.1007/s10585-004-8251-4.
  • Yang, W.-S., W.-Y. Wang, W.-Y. Fan, Q. Deng, and X. Wang. 2014. Tea consumption and risk of type 2 diabetes: a dose–response meta-analysis of cohort studies. British Journal of Nutrition 111:1329–39. doi:10.1017/S0007114513003887.
  • Yesair, D. W., A. R. Branfman, and M. M. Callahan. 1984. Human disposition and some biochemical aspects of methylxanthines. Progress in Clinical and Biological Research 158:215–33.
  • Yoshida, M., N. Kawano, and K. Yoshida. 2008. Control of sperm motility and fertility: Diverse factors and common mechanisms. Cellular and Molecular Life Sciences 65:3446–57. doi:10.1007/s00018-008-8230-z.
  • Youn, H., Y. Hee Kook, E.-T. Oh, S.-Y. Jeong, C. Kim, E. Kyung Choi, B. Uk Lim, and H. J. Park. 2009. 1-Methylxanthine enhances the radiosensitivity of tumor cells. International Journal of Radiation Biology 85:167–74. doi:10.1080/09553000902741190.
  • Zandvliet, A. S., A. D. R. Huitema, M. E. De Jonge, R. Den Hoed, R. W. Sparidans, V. M. Hendriks, W. Van Den Brink, J. M. Van Ree, and J. H. Beijnen. 2005. Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine. Basic & Clinical Pharmacology & Toxicology 96:71–79. doi:10.1111/j.1742-7843.2005.pto960111.x.
  • Zheng, G., K. Sayama, T. Okubo, L. R. Juneja, and I. Oguni. 2004. Anti-obesity effects of three major components of green tea, catechins, caffeine and theanine, in mice. in Vivo 18:55–62.
  • Zhou, B.-B. S., P. Chaturvedi, K. Spring, S. P. Scott, R. A. Johanson, R. Mishra, M. R. Mattern, J. D. Winkler, and K. K. Khanna. 2000. Caffeine abolishes the mammalian G2/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity. Journal of Biological Chemistry 275:10342–48. doi:10.1074/jbc.275.14.10342.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.