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α2C-adrenoceptor modulators: a patent review

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Pages 455-481 | Published online: 17 Mar 2011

Bibliography

  • Ahlquist RP. A study of the adrenotropic receptors. Am J Physiol 1948;153:586-600
  • Lands AM, Arnold A, McAuliff JP, Differentiation of receptor systems activated by sympathomimetic amines. Nature 1967;214:597-8
  • Langer SZ. Presynaptic regulation of catecholamine release. Biochem Pharmacol 1974;23:1793-800
  • Berthelsen S, Pettinger WA. A functional basis for classification of alpha-adrenergic receptors. Life Sci 1977;21:595-606
  • Michel MC, Kenny B, Schwinn DA. Classification of alpha 1-adrenoceptor subtypes. Naunyn Schmiedeberg's Arch Pharmacol 1995;352:1-10
  • MacDonald E, Kobilka BK, Scheinin M. Gene targeting-homing in on alpha2-adrenoceptor-subtype function. Trends Pharmacol Sci 1997;18:211-9
  • Hieble JP, Ruffolo RR Jr. Subclassification and nomenclature of alpha 1- and alpha 2-adrenoceptors. Prog Drug Res 1996;47:81-130
  • Hieble JP, Bondinell WE, Ruffolo RR Jr. alpha- and beta-Adrenoceptors: from the gene to the clinic. Part 1. Molecular biology and adrenoceptor subclassification. J Med Chem 1995;38:3415-44
  • Bylund DB, Eikenberg DC, Hieble JP, International union of pharmacology nomenclature of adrenoceptors. Pharmacol Rev 1994;46:121-36
  • Bylund DB. Alpha- and beta-adrenergic receptors: Ahlquist's landmark hypothesis of a single mediator with two receptors. Am J Physiol Endocrinol Metab 2007;293:E1479-81
  • Chalmers DT, Behan DP. The use of constitutively active GPCRs in drug discovery and functional genomics. Nat Rev Drug Discov 2002;1:599-608
  • Gerhardt MA, Neubig RR. Multiple Gi protein subtypes regulate a single effector mechanism. Mol Pharmacol 1991;40:707-11
  • Eason MG, Kurose H, Holt BD, Simultaneous coupling of alpha2-adrenergic receptors to two G-proteins with opposing effects. Subtype-selective coupling of alpha2C10, alpha2C4, and alpha2C2 adrenergic receptors to Gi and Gs. J Biol Chem 1992;267:15795-801
  • Eason MG, Jacinto MT, Liggett SB. Contribution to activation of alpha2-adrenergic receptor subtype coupling to Gs. Mol Pharmacol 1994;45:696-702
  • Kobilka BK, Matsui H, Kobilka TS, Cloning, sequencing and expression of the gene coding for the human platelet alpha2-adrenergic receptor. Science 1987;238:650-6
  • Regan JW, Kobilka TS, Yang-Feng TL, Cloning and expression of a human kidney cDNA for an alpha2-adrenergic receptor subtype. Proc Natl Acad Sci USA 1988;85:6301-5
  • Lomasney JW, Lorenz W, Allen LF, Expansion of the alpha2-adrenergic receptor family: cloning and characterization of a human alpha2-adrenergic receptor subtype, the gene for which is located on chromosome 2. Proc Natl Acad Sci USA 1990;87:5094-8
  • Weinshank RL, Zgombick JM, Macchi M, Cloning, expression, and pharmacological characterization of a human alpha2B-adrenergic receptor. Mol Pharmacol 1990;38:681-8
  • Zeng D, Harrison JK, D'Angelo DD, Molecular characterization of a rat alpha2B-adrenergic receptor. Proc Natl Acad Sci USA 1990;87:3102-6
  • Riess O, Thies U, Siedlaczck I, Precise mapping of the brain alpha2-adrenergic receptor gene within chromosome 4p16. Genomics 1994;19:298-302
  • Bousquet P. Imidazoline receptors: from basic concepts to recent developments. J Cardiovasc Pharmacol 1995;26:S1-6
  • Reis DJ, Bousquet P, Parini A. The imidazoline receptor: pharmacology, functions, ligands, and relevance to biology and medicine. Ann NY Acad Sci 1995;763:1-703
  • Gyires K, Zadori ZS, Torok T, Matyus P. alpha2-Adrenoreceptor subtypes-mediated physiological, pharmacological actions. Neurochem Int 2009;55:447-53
  • Tan CM, Limbird LE. The alpha2 adrenergic receptors: lessons from knockouts. In the adrenergic receptors in the 21st century. Humana Press, Inc., NJ; 2006. p. 241-65
  • Kable JW, Murrin LC, Bylund DB. In vivo gene modification elucidates subtype-specific functions of alpha2-adrenergic receptors. J Pharmacol Exp Ther 2000;293:1-7
  • MacMillan LB, Hein L, Smith MS, Central hypotensive effects of the alpha2a-adrenergic receptor subtype. Science 1996;273:801-3
  • Makaritsis KP, Handy DE, Johns C, Role of the alpha2B-adrenergic receptor in the development of salt-induced hypertension. Hypertension 1999;33:14-7
  • Philipp M, Brede M, Hein L. Physiological significance of alpha2-adrenergic receptor subtype diversity: one receptor is not enough. Am J Physiol Regul Integr Comp Physiol 2002;283:R287-95
  • Gaspar R, Gal A, Galik M, Different roles of alpha2-adrenoceptor subtypes in non-pregnant and late-pregnant uterine contractility in vitro in the rat. Neurochem Int 2007;51:311-8
  • Guo TZ, Davies MF, Kingery WS, Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice. Anesthesiology 1999;90:470-6
  • Hein L, Altman JD, Kobilka BK. Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission. Nature 1999;402:181-4
  • Bucheler MM, Haldamek K, Hein L. Two alpha2-adrenergic receptor subtypes, alpha2A and alpha2C, inhibit transmitter release in the brain of gene-targeted mice. Neuroscience 2002;109:819-26
  • Knaus AE, Muthig V, Schickinger S, alpha2-Adrenoceptor subtypes - Unexpected functions for receptors and ligands derived from gene-targeted mouse models. Neurochem Int 2007;51:277-81
  • Scheibner J, Trendelenburg AU, Hein L, Starke K. alpha2-adrenoceptors modulating neuronal serotonin release: a study in alpha2-adrenoceptor subtype-deficient mice. Br J Pharmacol 2001;132:925-33
  • Chotani MA, Flavahan S, Mitra S, Silent alpha2C-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries. Am J Physiol Heart Circ Physiol 2000;278:H1075-83
  • Chotani MA, Mitra S, Su BY, Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 2004;286:H59-67
  • Flavahan NA, Flavahan S, Mitra S, Chotani MA. The vasculopathy of Raynaud's phenomenon and scleroderma. Rheum Dis Clin North Am 2003;29:275-91
  • Bjorklund M, Sirvio J, Sallinen J, Alpha2C-adrenoceptor overexpression disrupts execution of spatial and non-spatial search patterns. Neuroscience 1999;88:1187-98
  • Tanila H, Mustonen K, Sallinen M, Riekkinen P Jr. Role of alpha2C-adrenoceptor subtype in spatial working memory as revealed by mice with targeted disruption of the alpha2C-adrenoceptor gene. Eur J Neurosci 1999;11:599-603
  • Rohrer DK, Kobilka BK. Insights from in vivo modification of adrenergic receptor gene expression. Annu Rev Pharmacol Toxicol 1998;38:351-73
  • Sallinen J, Haapalinna A, Viitamaa T, Adrenergic alpha2C-receptors modulate the acoustic startle reflex, prepulse inhibition, and aggression in mice. J Neurosci 1998;18:3035-42
  • Sallinen J, Haapalinna A, Viitamaa T, D-amphetamine and L-5-hydroxytryptophan-induced behaviours in mice with genetically-altered expression of the alpha2C-adrenergic receptor subtype. Neuroscience 1998;86:959-65
  • Scheinin M, Sallinen J, Haapalinna A. Evaluation of the alpha2C-adrenoceptor as a neuropsychiatric drug target. Studies in transgenic mouse models. Life Sci 2001;68:2277-85
  • Fairbanks CA, Stone LS, Kitto KF, alpha2C-Adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy. J Pharmacol Exp Ther 2002;300:282-90
  • Liggett SB, Shah SD, Cryer PE. Human tissue adrenergic receptors are not predictive of responses to epinephrine in vivo. Amer J Physiol 1989;256:E600-9
  • Van Campen LC, Visser FC, Visser CA. Ejection fraction improvement by beta-blocker treatment in patients with heart failure: an analysis of studies published in the literature. J Cardiovasc Pharmacol 1998;32:S31-5
  • Israel E, Drazen JM, Liggett SB, The effect of polymorphisms of the beta2-adrenergic receptor on the response to regular use of albuterol in asthma. Amer J Respir Crit Care Med 2000;162:75-80
  • Small KM, McGraw DW, Liggett SB. Pharmacology and physiology of human adrenergic receptor polymorphisms. Annu Rev Pharmacol Toxicol 2003;43:381-411
  • Small KM, Wagoner LE, Levin AM, Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure. N Engl J Med 2002;347:1135-42
  • Gerson MC, Wagoner LE, McGuire N, Liggett SB. Activity of the uptake-1 norepinephrine transporter as measured by I-123 MIBG in heart failure patients with a loss-of-function polymorphism of the presynaptic alpha2C-adrenergic receptor. J Nucl Cardiol 2003;10:583-9
  • Brede M, Wiesmann F, Jahns R, Feedback inhibition of catecholamine release by two different alpha2-adrenoceptor subtypes prevents progression of heart failure. Circulation 2002;106:2491-6
  • Small KM, Forbes SL, Rahman FF, A four amino acid deletion polymorphism in the third intracellular loop of the human alpha2C-adrenergic receptor confers impaired coupling to multiple effectors. J Biol Chem 2000;275:23059-64
  • University of Cincinnati. Methods of cardiovascular disease assessment in an individual. WO023101; 2004
  • University of Cincinnati. Alpha-2 adrenergic receptor polymorphisms. WO079561; 2001
  • University of Cincinnati. Alpha-2 adrenergic receptor polymorphisms. US0113725; 2003
  • University of Cincinnati. Alpha-2 adrenergic receptor polymorphisms. US7572603; 2009
  • University of Cincinnati. Polymorphisms and haplotypes of the alpha 2C adrenergic receptor gene. WO04939; 2006
  • Perlegen Sciences, Inc. Use of alpha-2 adrenergic receptor agonists. WO076655; 2006
  • Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology 2000;93:1345-9
  • Bekker A, Jorden VSB. Alpha-2 agonists in neuroanestesia. Semin Anesth Perio M 2004;23:181-91
  • Calasans-Maia JA, Zapata-Sudo G, Sudo RT. Dexmedetomidine prolongs spinal anestesia induced by levobupivacaine 0.5% in guinea-pigs. J Pharm Pharmacol 2005;57:1415-20
  • Kanazi GE, Aouad MT, Jabbour-Khoury SI, Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006;50:222-7
  • Deutsch E, Tobias JD. Hemodynamic and respiratory changes following dexmedetomidine administration during general anesthesia: sevoflurane vs desflurane. Pediatr Anesth 2007;17:438-44
  • Schmidt AP, Valinetti EA, Bertacchi MF, Effects of preanesthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Paediatr Anaesth 2007;17:667-74
  • Shukry M, Kennedy K. Dexmedetomidine as a total intravenous anesthetic in infants. Pediatr Anesth 2007;17:581-3
  • Laudenbach V, Mantz J, Lagercrantz H, Effects of alpha2-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine. Anesthesiology 2002;96:134-41
  • Paris A, Mantz J, Tonner PH, The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype. Anesth Analg 2006;102:456-61
  • Pertovaara A. Antinociceptive properties of fadolmidine (MPV-2426), a novel alpha2-adrenoceptor agonist. CNS Drug Rev 2004;10:117-26
  • Onttonen T, Pertovaara A. The mechanical antihyperalgesic effect of intrathecally administered MPV-2426, a novel alpha2-adrenoceptor agonist, in a rat model of postoperative pain. Anesthesiology 2000;92:1740-5
  • Xu M, Kontinen VK, Kalso E. Effects of radolmidine, a novel alpha2-adrenergic agonist compared with dexmedetomidine in different pain models in the rat. Anesthesiology 2000;93:473-81
  • Ansah OB, Pertovaara A. Peripheral suppression of arthritic pain by intraarticular fadolmidine, an alpha 2-adrenoceptor agonist, in the rat. Anesth Analg 2007;105:245-50
  • Niemi R, Huuskonen J, Laine K, Jarvinen T. Synthesis, hydrolysis, and intraocular pressure lowering effects of fadolmidine prodrugs. Int J Pharm 2005;295:121-7
  • Stone LS, MacMillan LB, Kitto KF, The alpha2a adrenergic receptor subtype mediates spinal analgesia evoked by alpha2 agonists and is necessary for spinal adrenergic-opioid synergy. J Neurosci 1997;17:7157-65
  • Messier TL, Dorman CM, Brauner-Osborne H, High throughput assays of cloned adrenergic, muscarinic, neurokinin, and neurotrophin receptors in living mammalian cells. Pharmacol Toxicol 1995;76:308-11
  • Pihlavisto M, Scheinin M. Functional assessment of recombinant human alpha2-adrenoceptor subtypes with cytosensor microphysiometry. Eur J Pharmacol 1999;385:247-53
  • Sullivan E, Tucker EM, Dale IL. Measurement of [Ca2+]using the fluorometric imaging plate reader (FLIPR). Methods Mol Biol 1999;114:125-33
  • Umland SP, Wan Y, Shah H, Receptor reserve analysis of the human alpha2C-adrenoreceptor using [35S]GTPgammaS and cAMP functional assays. Eur J Pharmacol 2001;411:211-21
  • Allergan Sales, Inc. Compounds as selective agonists as alpha 2B or 2B/2C adrenergic receptors. WO0586; 2001
  • Allergan Sales, Inc. Compounds and method of treatment having agonist-like activity selective at alpha 2B or 2B/2C adrenergic receptors. WO076950; 2002
  • Allergan Sales, Inc. Compounds and method of treatment having agonist-like activity selective at alpha 2B or 2B/2C adrenergic receptors. US023098; 2003
  • Allergan Sales, Inc. 7-[(1H-imidazol-4-yl)methyl]-5,6,7,8-tetrahydroquinoline. US179182; 2007
  • Allergan Sales, Inc. (2-Hydroxy)ethyl-thioureas useful as modulators of alpha2B adrenergic receptors. WO068384; 2002
  • Allergan Sales, Inc. Methods and compositions for modulating alpha adrenergic receptor activity. WO078702; 2001
  • Allergan Sales, Inc. Methods and compositions for modulating alpha adrenergic receptor activity. US058839; 2002
  • Dirig DM, Salami A, Rathbun ML, Characterization of variables defining hindpaw withdrawal latency evoked by radiant thermal stimuli. J Neurosci Methods 1997;76:183-91
  • Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992;50:355-63
  • Allergan Sales, Inc. Therapeutic fluoroethylcyano guanidines. US0255230; 2008
  • Allergan Sales, Inc. Substituted fluoroethyl ureas as alpha 2 adrenergic agents. US0255239; 2008
  • Allergan Sales, Inc. Aryl fluoroethyl ureas acting as alpha 2 adrenergic agents. US0194650; 2008
  • Allergan Sales, Inc. Therapeutic fluoroethyl ureas. US0270498; 2007
  • Allergan Sales, Inc. Substituted fluoroethyl ureas as alpha 2 adrenergic agents. WO09278; 2009
  • Allergan Sales, Inc. 4-Substituted imidazole-2-thiones and imidazol-2-ones as agonists of the alpha-2B and alpha-2C adrenergic receptors. WO099795; 2003
  • Allergan Sales, Inc. 4-(Substituted cycloalkylmethyl)imidazole-2-thiones, 4-(substituted cycloalkenylmethyl)imidazole-2-thiones, 4-(substituted cycloalkylmethyl)imidazol-2-ones and 4-(substituted cycloalkenylmethyl)imidazol-2-ones and related compounds. US0220402; 2004
  • Allergan Sales, Inc. 2-[(2-Thioxo-2,3-dihydro-1H-imidazol-4-yl)methyl]-3,4-dihydro-naphthalen-1(2H)-one. US0148872; 2006
  • Allergan Sales, Inc. Methods and compositions for the treatment of diabetes. US20293359; 2006
  • Allergan Sales, Inc. Unsubstituted and substituted 4-benzyl-1,3-dihydro-imidazole-2-thiones acting as specific or selective alpha2 adrenergic agonists and methods for using the same. US069142; 2006
  • Allergan Sales, Inc. 4-(Phenylmethyl and substituted phenylmethyl)-imidazole-2-thiones acting as specific alpha2 adrenergic agonists. WO036480; 2006
  • Allergan Sales, Inc. 4-(Condensed cyclicmethyl)-imidazole-2-thiones acting as alpha2 adrenergic agonists. US069144; 2006
  • Schering Corp. Alpha2C adrenoreceptor agonists. WO024949; 2007
  • Allergan Sales, Inc. Alpha-2 adrenergic agonists. US04789; 2007
  • Allergan Sales, Inc. Alpha-2 adrenergic agonists for the treatment of pain. WO05177; 2007
  • Allergan Sales, Inc. 4-(Substituted cycloalkylmethyl)imidazole-2-thiones, 4-(substituted cycloalkenylmethyl)imidazole-2-thiones, 4-(substituted cycloalkylmethyl)imidazol-2-ones and 4-(substituted cycloalkenylmethyl)imidazol-2-ones and related compounds. US072926; 2007
  • Allergan Sales, Inc. Methods and compositions for the treatment of hyperlipidemia. WO014299; 2008
  • Allergan Sales, Inc. Method of treating sensorimotor disorders with alpha-2 adrenergic receptor agonists. WO052073; 2009
  • Allergan Sales, Inc. Alpha 2B or 2B/2C adrenoceptor agonists for the treatment of neurodegeneration. WO032913; 2004
  • Allergan Sales, Inc. Therapeutic [(phenyl)imidazolyl]methylquinolinyl compounds. WO147788; 2008
  • Allergan Sales, Inc. Quinolynylmethylimidazoles as therapeutic agents. WO140138; 2009
  • Allergan Sales, Inc. Substituted-[aryl(imidazole)methyl]phenyl compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors. WO091735; 2009
  • Schering Corp. Imidazole derivatives as functionally selective alpha2C adrenoreceptor agonists. WO024944; 2007
  • Schering Corp. Functionally selective alpha2C adrenoreceptor agonists. WO100456; 2008
  • Schering Corp. Functionally selective alpha2C adrenoreceptor agonists. WO100457; 2008
  • Schering Corp. Functionally selective alpha2C adrenoreceptor agonists. US0197562; 2010
  • Schering Corp. Functionally selective alpha2C adrenoreceptor agonists. US027100; 2008
  • Schering Corp. Alpha2C adrenoreceptor agonists. US039439; 2008
  • Schering Corp. 3,4-Dihydro-1,4-benzoxazine, 3,4-dihydro-1,4-benzothiazine and 1,2,3,4-tetrahydro-quinoxaline derivatives as alpha2C adrenoreceptor agonists. WO100463; 2008
  • Schering Corp. Derivatives and analogs of chroman as functionally selective alpha2C adrenoreceptor agonists. WO100459; 2008
  • Merck. Derivatives and analogs of chroman as functionally selective alpha2C adrenoreceptor agonists. US0168195; 2010
  • F. Hoffmann-La Roche AG. Substituted 4-imidazoles. WO058867; 2008
  • Schering Corp. Functionally selective alpha2C adrenoreceptor agonists. WO105504; 2009
  • Schering Corp. Functionally selective alpha2C adrenoreceptor agonists. WO100480; 2008
  • Allergan Sales, Inc. Pharmaceutical compositions comprising (3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol. WO093930; 2010
  • Stoilov I, Watt DS, Goodman JP, Pyrek JST. Synthesis of detomidine and medetomidine metabolites: 1,2,3-trisubstituted arenes with 4′(5′)-imidazolylmethyl groups. J Heterocyclic Chem 1993;30:1645-51
  • Allergan Sales, Inc. Pyridine compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors. WO091209; 2010
  • Allergan Sales, Inc. Selective subtype alpha 2 adrenergic agents and methods for use thereof. WO140204; 2009
  • Allergan Sales, Inc. N-(1-phenyl-2-arylethyl)-4,5-dihydro-2H-pyrrol-5-amine compounds as subtype selective modulators of alpha2B or alpha2B and alpha2C adrenoceptors. US145061; 2010
  • Allergan Sales, Inc. Selective subtype alpha 2 adrenergic agents and methods for use thereof. WO091759; 2009
  • Allergan Sales, Inc. Oxazolidine and thiazolidine selective subtype alpha 2 adrenergic agents and methods for use thereof. WO091760; 2009
  • Allergan Sales, Inc. Selective subtype alpha 2 adrenergic agents and methods for use thereof. US0239918; 2009
  • Allergan Sales, Inc. Alpha2B and alpha2C agonists. US0275627; 2009
  • Allergan Sales, Inc. Selective subtype alpha 2 adrenergic agents and methods for use thereof. WO120648; 2009
  • Schering Corp. Alpha2C adrenoreceptor agonists. WO020578; 2009
  • Schering Corp. Fuctionally selective azanitrile alpha2C adrenoreceptor agonists. WO033495; 2010
  • Allergan Sales, Inc. Substituted-aryl-2-phenylethyl-1H-imidazole compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors. US0176843; 2009
  • Allergan Sales, Inc. Substituted-aryl-2-phenylethyl-1H-imidazole compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors. WO089132; 2009
  • Schering Corp. Cyclopropylchromene derivatives as modulators of the alpha-2C receptor. WO017120; 2010
  • Schering Corp. Biaryl spiroaminooxazoline analogues as alpha2C adrenergic receptor modulators. WO042473; 2010
  • Schering Corp. Spiroaminooxazoline analogues as alpha2C adrenergic receptor modulators. WO042475; 2010
  • Gentili F, Pigini M, Piergentili A, Giannella M. Agonists and antagonists targeting the different alpha2-adrenoceptor subtypes. Curr Top Med Chem 2007;7:163-86
  • Maura G, Bonanno G, Raiteri M. Presynaptic alpha2-adrenoceptors mediating inhibition of noradrenaline and 5-hydroxytryptamine release in rat cerebral cortex: further characterization as different alpha2-adrenoceptor subtypes. Naunyn Schmiedeberg's Arch Pharmacol 1992;345:410-16
  • Tellez S, Colpaert F, Marien M. Acetylcholine release in the rat prefrontal cortex in vivo: modulation by alpha2-adrenoceptor agonists and antagonists. J Neurochem 1997;68:778-85
  • Janssen Pharmaceutica N.V. Benzothieno[3,2-c]pyridines as alpha2 antagonists. WO020422; 2000
  • Orion Corp. Use of an alpha2-adrenoreceptor antagonist for CNS-related diseases. WO082825; 2003
  • Orion Corp. Derivatives of quinoline as alpha-2 antagonists. WO064645; 2001
  • Sallinen J, Hoglund I, Engstrom M, Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302. Brit J Pharmacol 2007;150:391-402
  • Massachusetts Menthal Health Inst. Treating alcohol and/or substance abuse by antagonizing alpha2 adrenergic receptors with weak dopamine blocking. WO034996; 2004
  • Fish & Richardson PC. Combinations of dopamine D2 receptor blockade with norepinephrine reuptake inhibition and with norepinephrine alpha 2 receptor blockade. US0188464; 2008
  • Janssen Pharmaceutica N.V. Triazolone, tetrazolone and imidazolone derivatives for use as alpha-2C adrenoreceptor antagonists. WO067139; 2006
  • Janssen Pharmaceutica N.V. Substituted pyrazinone derivatives for use as a medicine. WO122173; 2007
  • Janssen Pharmaceutica N.V. Substituted pyrazinone derivatives for use as a medicine. WO135131; 2007
  • Janssen Pharmaceutica N.V. Substituted pyrazinone derivatives as alpha 2C-adrenoreceptor antagonists. WO071639; 2007
  • Oy Juvantia Pharma Ltd. Antagonists for alpha-2 adrenoceptors. WO067513; 2004
  • Kyowa Hakko Kogyo Co., Ltd. Receptor antagonist. WO028732; 2003
  • Janssen Pharmaceutica N.V. Substituted amino isoxazoline derivatives and their use as anti-depressants. WO082878; 2003
  • Orion Corp. Polycyclic compounds as potent alpha2-adrenoceptor antagonists. WO082866; 2003
  • Finnegarn, Henderson, Farabow, Garrett & Dunner LLP. Polycyclic compounds as potent alpha2-adrenoceptor antagonists. US094740; 2006
  • Finnegarn, Henderson, Farabow, Garrett & Dunner LLP. Polycyclic compounds as potent alpha2-adrenoceptor antagonists. US0293527; 2007
  • Orion Corp. Polycyclic compounds as potent alpha2-adrenoceptor antagonists. US7592350; 2009
  • Richelson E, Souder T. Binding of antipsychotic drugs to human brain receptors-focus on newer generation compounds. Life Sc 2000;68:29-39
  • Mutlib AE, Strupczewski JT, Chesson SM. Application of hyphenated LC/NMR and LC/MS techniques in rapid identification of in vitro and in vivo metabolites of iloperidone. Drug Metab Dispos 1995;23:951-64
  • Novartis AG. Optical isomers of an iloperidone metabolite. WO020707; 2003
  • Taisho Pharmaceutical Co., Ltd. Cyclic amine compound. WO100355; 2005
  • Kyowa Hakko Kogyo Co., Ltd. Preparation of benzofuran derivatives as adrenaline alpha2c receptor antagonists. JP139106; 2005
  • Schering Corp. Benzodioxan analogues as alpha2C adrenergic receptor modulators. WO042477; 2010
  • Dabire H. Idazoxan: a novel pharmacological tool for the study of alpha2-adrenoceptors. J Pharmacol 1986;17:113-18
  • O'Rourke MF, Blaxall HS, Iversen LJ, Bylund DB. Characterization of [3H]RX821002 binding to alpha2-adrenergic receptor subtypes. J Pharmacol Exp Ther 1994;268:1362-7
  • Gentili F, Cardinaletti C, Vesprini C, alpha2-Adrenoreceptors profile modulation. 4. From antagonist to agonist behaviour. J Med Chem 2008;51:4289-99
  • Orion Corp. Aryl piperazines and their use as alpha2C antagonists. WO058060; 2010
  • Orion Corp. 2,3-Dihydrobenzo[1,4]dioxin-2-ylmethyl derivatives as alpha2C antagonists for use in the treatment of peripheric and central nervous system diseases. WO013390; 2009
  • Finnegarn, Henderson, Farabow, Garrett & Dunner LLP. 2,3-Dihydrobenzo[1,4]dioxin-2-ylmethyl derivatives as alpha2C antagonists for use in the treatment of peripheric and central nervous system diseases. US0216836; 2010
  • Zheng W, Lei L, Lalchandani SG, Yohimbine dimers exhibiting binding selectivities for human alpha2a- versus alpha2b-adrenergic receptors. Bioorg Med Chem Lett 2000;10:627-30
  • Lalchandani SG, Lei L, Zheng W, Yohimbine dimers exhibiting selectivity for the human alpha2C-adrenoreceptor subtype. J Pharmacol Exper Ther 2002;303:979-84
  • The University of Tennessee Research Foundation and the University of Mississippi. Yohimbine derivatives and use thereof. US7470703; 2008
  • The Ohio State University Research Foundation. Methods and compositions for treating Raynaud's phenomenon and scleroderma. US6444681; 2002
  • The Ohio State University Research Foundation. Methods and compositions for treating Raynaud's phenomenon and scleroderma. WO076502; 2000
  • Harker CT, Vanhoutte PM. Cooling the central ear artery of the rabbit: myogenic and adrenergic responses. J Pharmacol Exp Ther 1988;245:89-93
  • Del Bello F, Mattioli L, Ghelfi F, Fruitful adrenergic alpha2C-agonism/alpha2A-antagonism combination to prevent and contrast morphine tolerance and dependence. J Med Chem 2010;53:7825-35
  • Vacher B, Funes P, Chopin P, Rigid analogues of the alpha2-adrenergic blocker atipamezole: small changes, big consequences. J Med Chem 2010;53:6986-95

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