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Research Article

Drug Disposition in the Mammalian Eye and Brain: A Comparison of Mechanisms

Pages 133-246 | Published online: 22 Sep 2008

References

  • Oppenheimer S. B. Introduction to Embryonic Development. Allyn and Bacon, Boston 1980
  • Shepherd G. M. Synaptic Organisation of the Brain. Oxford University Press, London 1974
  • Betz A. L. Transport of ions across the blood-brain barrier. Fed. Proc 1986; 45: 2050–2054
  • Pardridge W. M., Choi T. B. Neutral amino acid transport at the human blood-brain barrier. Fed. Proc 1984; 45: 2073–2078
  • Pautler E. L., Tengerdy C. Transport of acidic amino acids by the bovine pigment epithelium. Exp. Eye Res. 1986; 43: 207–214
  • Goodchild M., Neal M. J. The uptake of 3H-7-aminobutyric acid by the retina. Brit. J. Pharmacol. 1973; 47: 529–542
  • Steele R. D. Blood-brain barrier transport of the a-keto acid analogs of amino acids. Fed. Proc 1986; 45: 2060–2064
  • Spector R., Eells J. Deoxynucleoside and vitamin transport into the central nervous system. Fed. Proc 1984; 43: 196–200
  • Heath H., Fiddick R. The active transport of ascorbic acid in the rat retina. Exp. Eye Res. 1966; 5: 156–163
  • Neal M. J., Gilroy J. High-affinity choline transport in the isolated retina. Brain Res. 1975; 93: 548–551
  • Cornford E. M., Braun L. D., Oldendorf W. H. Carrier mediated blood-brain barrier transport of choline and certain choline analogs. J. Neurochem. 1978; 30: 299–308
  • Banks W. A., Kastin A. J., Fischman A. J., Coy D. H., Strauss S. L. Carrier-mediated transport of enkephalins and /V-Tyr-MIF-1 across blood-brain barrier. Am. J. Physiol. 1986; 251: E477–E482
  • van Bree J. B. M. M., de Boer A. G., Verhoef J. C., Danhof M., Breimer D. D. Transport of vasopressin fragments across the blood-brain barrier: in vitro studies using monolayer cultures of bovine brain endothelial cells. J. Pharmacol. Exp. Ther. 1989; 249: 901–905
  • Bodor N. Novel approaches to the design of safer drugs: Soft drugs and site-specific chemical delivery systems. Adv. Drug Res. 1984; 13: 255–331
  • Lee V. H. L. Topical ocular drug delivery: recent advances and future perspectives. Pharmacy International 1985; 6: 135–138
  • Lee V. H. L., Urrea P. T., Smith R. E., Schanzlin D. J. Ocular drug bioavailability from topically applied liposomes. Survey Ophthalmol. 1985; 29: 335–348
  • Fraunfelder F. T., Meyer S. M. Drug-induced Ocular Side Effects and Drug Interactions. Lea and Febiger, Philadelphia 1988
  • Kremers J. J. M., van Norren D. Retinal damage in macaque after white light exposure lasting ten minutes to twelve hours. Invest. Ophthalmol. Vis. Sci. 1989; 30: 1032–1040
  • Varma S. D., Kumar S., Richards R. D. Light-induced damage to ocular lens cation pump: Prevention by vitamin C. Proc. Natl. Acad. Sci. USA 1979; 76: 3504–3506
  • Varma S. D., Rice D., Deleon-Cuello A. M., Richards R. D. Mechanism of in vitro photodynamic damage to lens. Lens Research 1984–1985; 2: 145–157
  • Kurnik R. T., Burde R. M., Becker B. Breakdown of the blood-aqueous barrier in the rabbit eye by infrared radiation. Invest. Opthalmol. Vis. Sci. 1989; 30: 717–722
  • Ohmori S., Nose H. Physical changes in bovine lens homoge-nate following ultraviolet irradiation and their prevention by some compounds. Chem. Pharm. Bull. 1985; 33: 2432–2437
  • Zigman S. Photobiology of the lens. Ocular Lens, Maisel. Dekker, New York 1985; 303–347
  • Ehling U., Krokowski E. Schaden durch Rontgenstrahlen am Kaninchenauge in Abhangigkeit von Dosis und Strahlenqualitat. Fortschr. Rontgenstrahlen und Nuklearmed. 1957; 86: 469–477
  • Matsuda H., Giblin F. J., Reddy V. N. The effect of X-irradiation on cation transport in rabbit lens. Exp. Eye Res. 1981; 33: 253–265
  • Matsuda H., Giblin F. J., Reddy V. N. The effect of X-irradiation on NaK ATPase and cation distribution in rabbit lens. Invest. Ophthalmol. Vis. Sci. 1982; 22: 180–185
  • Ehling U. H., Favor J., Kratochvilova J., Neuhauser-Klaus A. Dominant cataract mutations and specific-locus mutations in mice induced by radiation or ethylnitrosurea. Mutat. Res. 1982; 92: 181–192
  • Kratochvilova J., Favor J. Phenotypic characterization and genetic analysis of twenty dominant cataract mutations detected in offspring of irradiated male mice. Genet. Res., Camb. 1988; 52: 125–134
  • Ehling U. H. Induction and manifestation of hereditary cataracts. Assessment of Risk from Low-Level Exposure to Radiation and Chemicals, A. D. Woodhead, C. J. Shellabarger, V. Pond, A. Hollaender. Plenum. 1985; 345–367
  • Giblin F. J., McCready J. P., Schrimscher L., Reddy V. N. Peroxide-induced effects on lens cation transport following inhibition of glutathione reductase activity in vitro. Exp. Eye Res. 1987; 45: 77–91
  • West S., Munoz B., Emmett E. A., Taylor H. R. Cigarette smoking and risk of nuclear cataracts. Arch. Ophthalmol. 1989; 107: 1166–1169
  • Shearer T. R., David L. L., Anderson R. S. Selenite cataract: A review. Curr. Eye Res. 1987; 6: 289–300
  • Clark J. I., Danford M. E. Low Temperature and acrylamide inhibit lens opactification caused by calcium. Ophthalmic Res. 1985; 17: 246–250
  • Kinoshita J. H. Mechanisms initiating cataract formation. Invest. Ophthalmol. 1974; 13: 713–724
  • Simoons F. J. A geographic approach to senile cataract–Possible links with milk consumption, lactase activity, and galactose metabolism. Digest. Dis. Sci. 1982; 27: 257–264
  • Cotlier E., Apple D. Cataracts induced by the polypeptide antibiotic polymyxin B sulfate. Exp. Eye Res. 1973; 16: 69–77
  • Iwata S., Horiuchi M. Studies on experimental cataracts induced by ionophores: In vitro effects of nigericin and valinomycin on the lenses in mice. Exp. Eye Res. 1980; 31: 543–551
  • Mizuno G. R., Chapman C. J., Chipault J. R., Pfeifer D. R. Lipid composition and (Na+ + K+)-ATPase activity in rat lens during triparanol-induced cataract formation. Biochim. Biophys. Acta 1981; 644: 1–12
  • Hightower K. R., Harrison S. E. Valinomycin cataracts: The relative role of calcium and sodium accumulation. Exp. Eye Res. 1982; 34: 941–943
  • Horiuchi M., Iwata S. Effect of nigericin on distribution of sodium, potassium and calcium ion in rabbit lens. Exp. Eye Res. 1983; 37: 439–445
  • Calvin H. I., Medvedovsky C., Worgul B. V. Near-total glutathione depletion and age-specific cataracts induced by buthionine sulfoximine in mice. Science 1986; 233: 553–555
  • Bluming A. Z., Zeegen P. Cataracts induced by intermittent use of Decadron used as an antiemetic. J. Clin. Oncol. 1986; 4: 221–223
  • Dieperink H., Steinbriichel D., Kemp E., Svendsen P., Star-klint H. Cataractogenic effect of cyclosporin A: A new adverse effect observed in the rat. Nephrol. Dial. Transplant. 1987; 1: 251–253
  • Ellis E. F. Adverse effects of corticosteroid therapy. J. Allergy Clin. Immunol. 1987; 80: 515–517
  • Mandal K., Bose S. K., Chakrabarti B. Sensitizer-induced conformational changes in lens crystallin–I. Photodynamic action of methylene blue and W-formylkynurenine on bovine a-crystallin. Pho-tochem. Photobiol. 1986; 43: 515–523
  • Jernigan H. M., Jr. Role of hydrogen peroxide in riboflavin-sensitized photodynamic damage to cultured rat lenses. Exp. Eye Res. 1985; 41: 121–129
  • Rogers J. M., Grabowski C. T. Mirex-induced fetal cataracts: Lens growth, histology and cation balance, and relationship to edema. Teratology 1983; 27: 343–349
  • Hope-Ross M., Travers S., Mooney D. Solar retinopathy following religious rituals. Brit. J. Ophthalmol. 1988; 72: 931–934
  • Bernstein H. N., Ginsberg J. The pathology of chloroquine retinopathy. Arch. Ophthalmol. 1964; 71: 238–245
  • McFarlane J. R., Yanoff M., Scheie H. G. Toxic retinopathy following sparsomycin therapy. Arch. Ophthalmol. 1966; 76: 532–540
  • Henkes H. E., van Lith G. H. M., Canta L. R. Indomethacin retinopathy. Am. J. Ophthalmol. 1972; 73: 846–856
  • Davies S. C., Marcus R. E., Hungersford J. L., Miller M. H., Arden G. B., Huehns E. R. Ocular toxicity of high-dose intravenous desferoxamine. Lancet 1983; II: 181–184
  • Robinson W. G., Jr., Tillis T. N., Laver N., Kinoshita J. H. Diabetes-related histopathologies of the rat retina prevented with an aldose reductase inhibitor. Exp. Eye Res. 1990; 50: 355–366
  • Potts A. M. Toxic responses of the eye. Casaretts and Doulls Toxicology, the Basic Science of Poisons, 3rd ed., C. D. Klaassen, M. O. Amdur, J. Doull. Macmillan, New York 1986; 478–515
  • Cserr H. F. Physiology of the choroid plexus. Physiol. Rev. 1971; 51: 273–311
  • Benson H. Permeability of the cornea to topically applied drugs. Arch. Ophthalmol. 1974; 91: 313–327
  • Rapoport S. I. Blood-Brain Barrier in Physiology and Medicine. Raven Press, New York 1976
  • Raviola G. The structural basis of the blood-ocular barriers. Exp. Eye Res. suppl. 1977; 27, 63
  • Mason C. G. Ocular accumulation and toxicity of certain system-ically administered drugs. J. Toxicol. Environ. Health 1977; 2: 977–995
  • Bradbury M. The Concept of the Blood-Brain Barrier. Wiley, Chichester 1979
  • Bito L. Z., DeRousseau C. J. Transport functions of the blood-retinal barrier system and the microenvironment of the retina. The Blood-Retinal Barriers, J. Cunha-Vaz. Plenum Press, New York 1979; 133–163
  • Reddy V. N. Dynamics of transport systems in the eye. Invest. Ophthalmol. Vis. Sci. 1979; 18: 1000–1018
  • Burstein N. L. Corneal cytotoxicity of topically applied drugs, vehicles and preservatives. Survey Ophthalmol. 1980; 25: 15–30
  • Wiederholt M. Physiology of epithelial transport in the human eye. Klin. Wochenschr. 1980; 58: 975–984
  • Shichi H., Nebert D. W. Drug metabolism in ocular tissues. Extrahepatic Metabolism of Drugs and Other Foreign Compounds, T. E. Gram. S. P. Medical & Scientific Books, New York 1980; 333–363
  • Zimmerman T. J., Leader B., Kaufman H. E. Advances in ocular pharmacology. Ann. Rev. Pharmacol. Toxicol. 1980; 20: 415–428
  • Mishima S. Clinical pharmacokinetics of the eye. Invest. Ophthalmol. Vis. Sci. 1981; 21: 504–541
  • Shell J. W. Pharmacokinetics of topically applied ophthalmic drugs. Survey Ophthalmol. 1982; 26: 207–218
  • Gjedde A. Modulation of substrate transport to the brain. Acta Neurol. Scand. 1983; 67: 3–25
  • Auricchio G., Libondi T. The physiologic and pharmacologic factors protecting the lens transparency and the update approach to the prevention of experimental cataracts: A review. Metabolic, Pediatric and Systemic Ophthalmology 1983; 7: 115–124
  • Moller J. V., Sheikh M. I. Renal organic anion transport system: Pharmacological, physiological and biochemical aspects. Pharmacol. Rev. 1983; 34: 315–358
  • Mesnil M., Testa B., Jenner P. Xenobiotic metabolism by brain monooxygenases and other cerebral enzymes. Adv. Drug Res. 1984; 13: 95–207
  • Mathias R. T., Rae J. L. Transport properties of the lens. Am. J. Physiol. 1985; 249: C181–C190
  • Kador P. F., Kinoshita J. H., Sharpless N. E. Aldose reductase inhibitors: A potential new class of agents for the pharmacological control of certain diabetic complications. J. Med. Chem. 1985; 28: 841–849
  • Cornford E. M. The blood-brain barrier, a dynamic regulatory interface. Mol. Physiol. 1985; 7: 219–260
  • Kador P. F., Robison W. G., Jr., Kinoshita J. H. The pharmacology of aldose reductase inhibitors. Ann. Rev. Pharmacol. Toxicol. 1985; 25: 691–714
  • Koneru P. B., Lien E. J., Koda R. T. Review: Oculotoxicities of systemically administered drugs. J. Ocul. Pharmacol. 1986; 2: 385–404
  • McLane N. J., Carroll D. M. Ocular manifestations of drug abuse. Survey Ophthalmol. 1986; 30: 298–313
  • Wright C. E., Tallan H. H., Lin Y. Y. Taurine: Biological update. Ann. Rev. Biochem. 1986; 55: 427–453
  • Besseghir K., Roch-Ramel F. Renal excretion of drugs and other xenobiotics. Renal Physiol. 1987; 10: 221–241
  • Pardridge W. M. Recent advances in blood-brain transport. Ann. Rev. Pharmacol. Toxicol. 1988; 28: 25–39
  • Taylor R., Agius L. The biochemistry of diabetes. Biochem. J. 1988; 250: 625–640
  • Rose R. C. Transport of ascorbic acid and other water-soluble vitamins. Biochim. Biophys. Acta 1988; 947: 335–366
  • Parke D. V. The Biochemistry of Foreign Compounds. Pergamon Press, Oxford 1968
  • Vaughan D., Asbury T. General Ophthalmology 10th ed. Lange Publications. 1983
  • Goldman E. Vitalfarbung am Zentralnervensystem. Abhandl. Preuss. Akad. Wiss. Phys.-Math. K. 1913; I: 1–60
  • Schnaudigel O. Albrecht von Graefes Arch. Ophthalmol. 1913; 86: 93–97, as cited by Cunha-Vaz [85]
  • Palm E. On the occurrence in the retina of conditions corresponding to the “blood-brain barrier,”. Acta Ophthalmol. 1947; 25: 29–35
  • Cunha-Vaz J. G., Shakib M., Ashton N. Studies on the permeability of the blood-retinal barrier. I. On the existence, development, and site of a blood-retinal barrier. Brit. J. Ophthalmol. 1966; 50: 441–453
  • Bellhorn R. W. Permeability of blood-ocular barriers of neonatal and adult cat to sodium fluorescein. Invest. Ophthalmol. Vis. Sci. 1980; 19: 870–877
  • Maurice D. M. The use of fluorescein in ophthalmological research. Invest. Ophthalmol. 1967; 6: 464–477
  • Maurice D. M., Mishima S. Ocular pharmacokinetics. Pharmacology of the Eye, Handbook of Experimental Pharmacology, M. L. Sears. Springer-Verlag, New York 1984; Vol. 69: 19–116
  • Cunha-Vaz J. Sites and functions of the blood-retinal barriers. The Blood-Retinal Barriers, J. Cunha-Vaz. Plenum Press, New York 1979; 101–117
  • Newell F. W. Ophthalmology, Principles and Concepts, 6th ed. Mosby. 1986
  • Betz A. L., Goldstein G. W. Transport of hexoses, potassium and neutral amino acids into capillaries isolated from bovine retina. Exp. Eye Res. 1980; 30: 593–605
  • Crosson C. E., Pautler E. L. Glucose transport across isolated bovine pigment epithelium. Exp. Eye Res. 1982; 35: 371–377
  • Khatami M., Li W., Rockey J. H. Kinetics of ascorbate transport by cultured retinal capillary pericytes. Inhibition by glucose. Invest. Ophthalmol. Vis. Sci. 1986; 27: 1665–1671
  • Khatami M., Stramm L. E., Rockey J. H. Ascorbate transport in cultured cat retinal pigment epithelial cells. Exp. Eye Res. 1986; 43: 607–615
  • Reddy V. N., Thompson M. R., Chakrapani B. Amino acid transport across blood-aqueous barrier of mammalian species. Exp. Eye Res. 1977; 25: 555–562
  • Edwards R. B. Accumulation of taurine by cultured retinal pigment epithelium of the rat. Invest. Ophthalmol. Vis. Sci. 1977; 16: 201–208
  • Kador R F., Jernigan H. M., Jr., Kinoshita J. H. Accumulation and incorporation of radiolabeled choline into cultured rabbit lenses: Evidence for a choline transport system. Exp. Eye Res. 1980; 30: 1–11
  • Walinder R E. The accumulation of alpha-aminoisobutyric acid by rabbit ciliary body-iris preparations. Invest. Ophthalmol. 1968; 7: 67–76
  • Reddy V. N. Studies on intraocular transport of taurine. I. Accumulation in rabbit ciliary body-iris preparation in vitro. Biochim. Bio-phys. Acta 1968; 158: 246–254
  • Coben L. A., Cotlier E., Beaty C., Becker B. Proline transport by rabbit ciliary body-iris in vitro. Invest. Ophthalmol. 1970; 9: 949–958
  • Reddy V. N. Transport of organic molecules in the lens. Exp. Eye Res. 1973; 15: 731–750
  • Cotlier E., Beaty C. The transport of 14C-a-aminoisobutyric acid in galactose cataracts in rats and rabbit lenses incubated in high galactose media. Invest. Ophthalmol. 1968; 7: 77–87
  • Reddy V. N. Studies on intraocular transport of taurine. II. Accumulation in the rabbit lens. Invest. Ophthalmol. 1970; 9: 206–219
  • Becker B. Ascorbate transport in guinea pig eyes. Invest. Ophthalmol. 1967; 6: 410–415
  • Chu T. -C., Candia O. A. Active transport of ascorbate across the isolated rabbit ciliary epithelium. Invest. Ophthalmol. Vis. Sci. 1988; 29: 594–599
  • Delamere N. A., Williams R. N. A comparative study on the uptake of ascorbic acid by the iris-ciliary body of the rabbit, guinea pig and rat. Comp. Biochem. Physiol. 1987; 88B: 847–849
  • Stone R. A. Cholic acid accumulation by the ciliary body and by the iris of the primate eye. Invest. Ophthalmol. Vis. Sci. 1979; 18: 819–826
  • Stone R. A. The transport of para-aminohippuric acid by the ciliary body and by the iris of the primate eye. Invest. Ophthalmol. Vis. Sci. 1979; 18: 807–818
  • Kern H. L. Accumulation of amino acids by calf lens. Invest. Ophthalmol. 1962; 1: 368–376
  • Varma S. D., Chakrapani B., Reddy V. N. Intraocular transport of myoinositol. II. Accumulation in the rabbit lens in vitro. Invest. Ophthalmol. 1970; 9: 794–800
  • Shiono T., Kador P. F., Kinoshita J. H. Ornithine accumulation and metabolism in rat lens. Exp. Eye Res. 1985; 40: 421–429
  • DiBenedetto F. E., Bito L. Z. The kinetics and energy dependence of prostaglandin transport processes. I In vitro studies on the rate of PGF2ct accumulation by the rabbit anterior uvea. Exp. Eye Res. 1980; 30: 175–182
  • Socci R. R., Delamere N. A. Characteristics of ascorbate transport in the rabbit iris-ciliary body. Exp. Eye Res. 1988; 46: 853–861
  • Becker B., Forbes M. Iodopyracet (Diodrast) transport by the rabbit eye. Am. J. Physiol. 1961; 200: 461–464
  • Barany E. H. In vitro uptake of bile acids by choroid plexus and anterior uvea. I. The iodipamide-sensitive transport systems in the rabbit. Acta Physiol. Scand. 1975; 93: 250–268
  • Stone R. A., Wilson C M. Fluorescein transport in the anterior uvea. Invest. Ophthalmol. Vis. Sci. 1982; 22: 303–309
  • Cantrill H. L., Pederson J. E. Experimental retinal detachment. VI. The permeability of the blood-retinal barrier. Arch. Ophthalmol. 1984; 102: 747–751
  • Matsumoto S., Araie M., Takase M. Active transport of beta-adrenergic blocking agents in the anterior uvea of albino rabbit. Japan. J. Ophthalmol. 1986; 30: 339–350
  • Mochizuki M. Transport of indomethacin in the anterior uvea of the albino rabbit. Japan J. Ophthalmol. 1980; 24: 363–373
  • Stramm L. E., Pautler E. L. Glucose uptake by normal and dystrophic rat retinas and ciliary bodies. Exp. Eye Res. 1980; 30: 709–718
  • Paterson S. J., Wilson W. S. Uptake of choline by rabbit corneal epithelium. Brit. J. Pharmacol. 1977; 59: 499P
  • Di Mattio J., Zadunaisky J. A. Glucose transport into the ocular compartments of the rat. Exp. Eye Res. 1981; 32: 517–532
  • Di Mattio J. A comparative study of ascorbic acid entry into aqueous and vitreous humors of the rat and guinea pig. Invest. Ophthalmol. Vis. ScL 1989; 30: 2320–2331
  • Kern H. L., Zolot S. L. Transport of vitamin C in the lens. Curr. Eye Res. 1987; 6: 885–896
  • Audus K. L., Borchardt R. T. Transport of macromolecules across the capillary endothelium. Handbook of Experimental Pharmacology, R. L. Juliano. Springer-Verlag, Berlin, in press
  • Patil P. N. Some factors which affect the ocular drug responses. Trends Pharmacol. Sci. 1984; 5: 201–204
  • Schoenwald R. D. Ocular Drug Delivery. Pharmacokinetic Considerations. Clin. Pharmacokinet. 1990; 18: 255–269
  • Piatigorsky J. Lens crystallins and their genes: Diversity and tissue-specific expresion. FASEB J. 1989; 3: 1933–1940
  • Kinsey V. E., Reddy D. V. N. Studies on the crystalline lens. XI. The relative role of the epithelium and capsule in transport. Invest. Ophthalmol. 1965; 4: 104–116
  • Kern H. L., Ho C. -K., Ostrove S. A. Comparison of transport at the anterior and posterior surfaces of the calf lens. Exp. Eye Res. 1977; 24: 559–570
  • Christensen H. N. Recognition sites for material transport and information transfer. Current Topics in Membranes and Transport, F. Bronner, A. Kleinzeller. Academic Press. 1975; 227–258
  • Reddy V. N., Varma S. D., Chakrapani B. Intraocular transport of myoinositol. I. Accumulation in rabbit ciliary body. Invest. Ophthalmol. 1970; 9: 785–793
  • Brassil D., Kern H. L. Characterization of the transport of neutral amino acids by the calf lens. Invest. Ophthalmol. 1968; 7: 441–451
  • Cotlier E., Myo-inositol. Active transport by the crystalline lens. Invest. Ophthalmol. 1970; 9: 681–691
  • Reddy V. N., Varma S. D., Chakrapani B. Transport and metabolism of glutathione in the lens. Exp. Eye Res. 1973; 16: 105–114
  • Kern H. L., Ho C. -K. Transport of dicarboxylic amino acids in the rat lens. Ophthal. Res. 1974; 6: 166–174
  • Smith E. L., Hill R. L., Lehman I. R., Lefkowitz R. J., Handler P., White E. Principles in Biochemistry–Mammalian Biochemistry, 7th ed. McGraw-Hill. 1983; 663
  • Downes C. P. The cellular functions of myo-inositol. Biochem. Soc. Trans. 1989; 17: 259–266
  • Maekawa S., Hibasami H., Uji Y., Nakashima K. Active transport and metabolic characteristics of polyamines in the rat lens. Bio-chim. Biophys. Acta 1989; 993: 199–203
  • Reddy D. V. N. Studies on intraocular transport of taurine. I. Accumulation in rabbit ciliary body-iris preparation in vitro. Biochim. Biophys. Acta 1968; 158: 246–254
  • Cayen M. N., Hicks D. R., Ferdinandi E. S., Kraml M., Grese-lin E., Dvornick D. Metabolic disposition and pharmacokinetics of the aldose reductase inhibitor tolrestate in rats, dogs, and monkeys. DrugMetab. Dispos. 1985; 13: 412–419
  • Park Y. H., Woolbridge C. B., Mattern J., Stoltz M. L., Brazzell R. K. Disposition of the aldose reductase inhibitor AL01576. J. Pharm. Sci. 1985; 77: 110–115
  • Graham D. J. M., Hama K. M., Smith S. A., Kurz L., Chaplin M. D., Hall D. J. Disposition of namfimidone in rats. Drug Me-tabol. Dispos. 1987; 15: 565–570
  • Kobayashi T., Hohnoki H., Esumi Y., Ohtsuki T., Washino T., Tanayama S. Metabolism and disposition of (RS)-2-methoxy-3-(octadecylcarbamoyloxy)propyl 2-(3-thiazolio)ethyl phosphate (MOTP) in rats and dogs. Xenobiotica 1988; 18: 49–59
  • Tremaine L. M., Welch W. M., Ronfeld R. A. Metabolism and disposition of the 5-hydroxytryptamine uptake blocker sertraline in the rat and dog. Drug. Metabol. Dispos. 1989; 17: 542–550
  • Potts A. M. The concentration of phenothiazines in the eye of experimental animals. Invest. Ophthalmol. 1962; 1: 522–530
  • McChesney E. W., Banks W. F., Jr., Sullivan D. J. Metabolism of chloroquine and hydroxychloroquine in albino and pigmented rats. Toxicol. Appl. Pharmacol. 1965; 7: 627–636
  • Basu P. K., Matuk Y., Kapur B. M., Avaria M., Jankie R., Carre F. Ocular distribution of sodium pentobarbital after injection of lethal and anesthetic doses and after transfer via corneal grafting. Can. J. Ophthalmol. 1984; 19: 126–129
  • Valeri P., Romanelli L., de Paolis L., Martinelli B. Ocular distribution of aspirin and salicylate following systemic administration of aspirin to rabbits. J. Pharm. Pharmacol. 1988; 40: 823–824
  • Tabbara K. F., O'Connor G. R. Ocular tissue absorption of clindamycin phosphate. Arch. Ophthalmol. 1975; 93: 1180–1185
  • Bloome M. A., Golden B., McKee A. P. Antibiotic concentrations in ocular tissues. Arch. Ophthalmol. 1970; 83: 78–83
  • Fantes F. E., Heuer D. K., Parrish R. K., II, Sossi N., Gressel M. G. Topical fluorouracil–pharmacokinetics in normal rabbit eyes. Arch. Ophthalmol. 1985; 103: 953–955
  • Chen C. C., Anderson J., Shackleton M., Attard J. The disposition of bunolol in the rabbit eye. J. Ocular Pharmacol. 1987; 3: 149–157
  • Wei C., Anderson J. A., Leopold I. Ocular absorption and metabolism of topically applied epinephrine and a dipivalyl ester of epinephrine. Invest. Ophthalmol. Vis. Sci. 1978; 17: 315–321
  • Wiederholt M., Kossendrup D., Schulz W., Hoffmann F. Pharmacokinetics of topical cyclosporin A in the rabbit eye. Invest. Ophthalmol. Vis. Sci. 1986; 27: 519–524
  • Potts A. M. The reaction of uveal pigment in vitro with polycyclic compounds. Invest. Ophthalmol. 1964; 3: 405–417
  • Potts A. M. Further studies concerning the accumulation of polycyclic compounds on uveal melanin. Invest. Ophthalmol. 1964; 3: 399–404
  • Poynter D., Martin L. E., Harrison C., Cook J. Affinity of la-betalol for ocular melanin. Brit. J. Clin. Pharmacol. 1976; 711–721, suppl.
  • Aula P., Kaila T., Huupponen R., Salminen L. Timolol binding to bovine ocular melanin in vitro. J. Ocular Pharmacol. 1988; 4: 29–36
  • Lyons J. S., Krohn D. L. Pilocarpine uptake by pigmented uveal tissue. Am. J. Ophthalmol. 1973; 75: 885–888
  • Patil P. N., Trendelenburg U. The extraneuronal uptake and metabolism of 3H-isoprenaline in the rabbit iris. Nauyn-Schmiedeberg's Arch. Pharmacol. 1982; 318: 158–165
  • Shimada K., Baweja R., Sokoloski T., Patil P. N. Binding char-actersitics of drugs to synthetic levodopa melanin. J. Pharm. Sci. 1976; 65: 1057–1060
  • Atlasik B., Stepien K., Wilczok T. Interaction of drugs with ocular melanin in vitro. Exp. Eye Res. 1980; 30: 325–331
  • Patil P. N. Cocaine-binding by the pigmented and the nonpigmented iris and its relevance to the mydriatic effect. Invest. Ophthalmol. 1972; II: 739–746
  • Salazar M., Patil P. N. An explanation for the long duration of mydriatic effect of atropine in the eye. Invest. Ophthalmol. 1976; 15: 671–673
  • Urtti A., Salminen L., Kujari H., Jantti V. Effect of ocular pigmentation of pilocarpine pharmacology in the rabbit eye. II. Drug response. Int. J. Pharmaceutics 1984; 19: 53–61
  • Salminen L., Urtti A., Periviita L. Effect of ocular pigmentation on pilocarpine pharmacology in the rabbit eye. I. Drug distribution and metabolism. Int. J. Pharmaceutics 1984; 18: 17–24
  • Obianwu H. O., Rand M. J. The relationship between the mydriatic aeon of aphedrine and the colour of the iris. Brit. J. Ophthalmol. 1965; 49: 264–270
  • Schwartzman M. L., Masferrer J., Dunn M. W., McGiff J. C., Abraham N. G. Cytochrome P-450, drug-metabolizing enzymes and arachidonic acid metabolism in bovine ocular tissues. Curr. Eye Res. 1987; 6: 623–630
  • Sakamoto S., Shichi H. Induction of alkoxyresorufin O-dealkylase and UDP-glucuronosyl transferase by phenobarbital and 3-methylcholanthrene in primary cultures of porcine ciliary epithelial cells. Biochem. Pharmacol., in press
  • Das N. D., Shichi H. Enzymes of mercapturate synthesis and other drug-metabolizing reactions–specific localization in the eye. Exp. Eye Res. 1981; 33: 525–533
  • Shichi H., Tsunematsu Y., Nebert D. W. Aryl hydrocarbon hydroxylase induction in retinal pigmented epithelium: Possible association of genetic differences in a drug-metabolizing enzyme system with retinal degeneration. Exp. Eye Res. 1976; 23: 165–176
  • Goos C. M.A. A., Hukkelhoven M. W. A. C., Ver-morken A. J. M., Henderson P. T., Bloemendal H. Metabolism of ben-zo(a)pyrene in bovine lens epithelium. Exp. Eye Res. 1981; 33: 345–350
  • Shichi H., Atlas S. A., Nebert D. W. Genetically regulated aryl hydrocarbon hydroxylase induction in the eye: Possible significance of the drug-metabolizing enzyme system for the retinal pigmented epithelium-choroid. Exp. Eye Res. 1975; 21: 557–567
  • Kishida K., Matsumoto K., Manabe R., Sugiyama T. Cytochrome P-450 and related components of the microsomal electron transport system in the bovine ciliary body. Curr. Eye Res. 1986; 5: 529–533
  • Aimoto T., Chiou G. C. Y. 7-Ethoxycoumarin deethylase activity as indicator of oxidative metabolism in rabbit eyes. J. Ocular Pharmacol. 1985; 1: 279, 286
  • Gallegos A. J., Partida P. D., Garzon P. The presence of 68-steroid hydroxylase in human cornea. J. Steroid Biochem. 1976; 7: 135–137
  • Vermorken A. J. M., De R., Waal W. J. M., van De VenBloemendal H., Henderson P. T. Hydroxylation of dehydroepiandros-terone in the eye lens. Biochim. Biophys. Acta 1977; 496: 495–506
  • Vermorken A. J. M., van de Ven W. J. M., Gielen W. H. J., Bloemendal H., Ketelaars H C.J. Metabolism of dehydroepi-androsterone in the eye lens epithelium. Exp. Eye Res. 1977; 24: 263–270
  • Abraham N. G., Lin J. H.-C., Dunn M. W., Schwartzman M. Presence of heme oxygenase and NADPH cytochrome P-450(c) reductase in human corneal epithelium. Invest. Ophthalmol. Vis. Sci. 1987; 28: 1464–1472
  • Shanthaveerappa T. R., Bourne G. H. Monoamine oxidase distribution in the rabbit eye. J. Histochem. Cytochem. 1964; 12: 281–287
  • Thomas T. N., Sparks D. L., Buckholtz N. S., Zemp J. W. Monoamine oxidase activity in retina–distribution and drug inhibition. Abstr. Soc. for Neurosci. 1979; 5: 810
  • Waltman S., Sears M. Catechol-O-methyltransferase and monoamine oxidase activity in the ocular tissues of albino rabbits. Invest. Ophthalmol. 1964; 3: 601–605
  • Kremzner L. T., Roy D., Spector A. Polyamines in normal and cataractous humans lenses: Evidence for post-translational modification. Exp. Eye Res. 1983; 37: 649–659
  • Crabbe M. J. C. Ocular diamine oxidase activity. Exp. Eye Res. 1985; 41: 777–778
  • Ellis P. P., Littlejohn K., Deitrich R. A. Enzymatic hydrolysis of pilocarpine. Invest. Ophthalmol. 1972; 11: 747–751
  • Lavallee W. F., Rosenkrantz H. Evidence for pilocarpine transformation by serum. Biochem. Pharmacol. 1966; 15: 206–210
  • Lee V. H. L. Esterase activities in adult rabbit eyes. J. Pharm. Sci. 1983; 72: 239–244
  • Michon J., Jr., Kinoshita J. H. Cholinesterase in the lens. Arch. Ophthalmol. 1967; 77: 804–808
  • Leinweber F. -J. Possible physiological roles of carboxylic ester hydrolases. Drug Metab. Rev. 1987; 18: 379–439
  • Rush R. S., Main A. R., Miller S. K., Kirkpatrick B. F. Resolution and purification of two monomeric butyrylcholine esterases from rabbit liver. J. Biol. Chem. 1980; 255: 7155–7157
  • Billiar R. B., Eiknes K. B. Use of cholinesterase for hydrolysis of steroid acetates. Anal. Biochem. 1965; 13: 11–18
  • Mentlein R. The tumor promoter 12-O-tetradecanoyI phorbol 13-acetate and regulatory diacylglycerols are substrates for the same carboxylic esterase. J. Biol. Chem. 1986; 261: 7816–7818
  • Lockridge O., Motthershaw-Jackson N., Eckerson H. W., LaDu B. N. Hydrolysis of diacetylmorphine (heroin) by human serum cholinesterase. J. Pharmacol. Exp. Ther. 1980; 215: 1–8
  • Stewart D. J., Inaba T., Tang B. K., Kalow W. Hydrolysis of cocaine in human plasma by cholinesterase. Life Sci. 1977; 20: 1557–1564
  • Main A. R. Purification and properties of plasma cholinesterases. Rev. Biochem. Toxicol. 1984; 6: 117–154
  • Anderson J. A., Richman J. B., Mindel J. S. Effects of echo-thiophate on enzymatic hydrolysis of dipivefrin. Arch. Ophthalmol. 1984; 102: 913–916
  • Philipson B., Kaufman P. L., Fagerholm P., Axelsson U., Barany E. H. Echothiophate cataracts in monkeys. Arch. Ophthalmol. 1979; 97: 340–346
  • Lockridge O. Substance P hydrolysis by human serum choline-sterase. JNeurochem. 1982; 39: 106–110
  • Boopathy R., Balasubramanian A. S. A peptidase activity exhibited by human pseudocholinesterase. Eur. J. Biochem. 1987; 162: 191–197
  • Chubb I. W., Hodgson A. J., White G. H. Acetylcholinesterase hydrolyzes substance P. Neuroscience 1980; 5: 2065–2072
  • Chubb I. W., Ranieri E., White G. H., Hodgson A. J. The enkephalins are amongst the peptides hydrolyzed by purified acetylcholinesterase. Neuroscience 1983; 10: 1369–1377
  • Nichols C. W., Koelle G. B. Acetylcholinesterase: Method for demonstration in amacrine cells of rabbit retina. Science 1967; 155: 477–478
  • Petersen R. A., Lee K. -J., Donn A. Acetylcholinesterase in the rabbit cornea. Arch. Ophthalmol. 1965; 73: 370–377
  • Lee V. H. L., Chang S. -C., Oshiro C. M., Smith R. E. Ocular esterase composition in albino and pigmented rabbits: Possible implications in ocular prodrug design and evaluation. Curr. Eye Res. 1985; 4: 1117–1125
  • Moore D. E., Hess G. P. Acetylcholinesterase-catalyzed hydrolysis of an amide. Biochemistry 1975; 14: 2386–2389
  • Hara S., Hayasaka S., Mizuno K. Distribution and some properties of lysosomal arylsulfatases in the bovine eye. Exp. Eye Res. 1979; 28: 641–650
  • Dutton G. J. Glucuronidation of Drugs and Other Compounds. CRC Press, Boca Raton, FL 1966
  • Hayasaka S., Shiono T. Postnatal changes in lysosomal enzymes of rabbit ocular tissues. Exp. Eye Res. 1982; 34: 571–575
  • Price G., Tsui J., Unakar N. Arylsulfatases in normal and cat-aractous rat lens. Micron 1982; 13: 471–472
  • Price G., Tsui J., Unakar N. J. Arylsulfatase–Cytochemical localization in lenses of normal and galactose-fed rats. Curr. Eye Res. 1981/1982; 1: 567–577
  • Harries W., Tsui J., Unakar N. J. Ultrastructural cytochemistry: Effect of Sorbinil on arylsulfatases in cataractous lenses. Curr. Eye Res. 1985; 4: 657–666
  • Tanimoto T., Fukuda H., Kawamura J. Purification and some properties of aldose reductase from rabbit lens. Chem. Pharm. Bull. 1983; 31: 2395–2403
  • Kador P. F., Kinoshita J. H., Brittain D. R., Sennitt C. M., Stribling D., Mirrlees D. J. Purified rat lens aldose reductase. Polyol production in vitro and its inhibition by aldose reductase inhibitors. Biochem. J. 1986; 240: 233–237
  • Okuda J., Miwa I., Inagaki K., Horie T., Nakayama M. Inhibition of aldose reductases from rat and bovine lenses by fla-vonoides. Biochem. Pharmacol. 1982; 31: 3807–3822
  • del Corso A., Barsacchi D., Camici M., Garland D., Mura U. Bovine lens aldose reductase: Identification of two enzyme forms. Arch. Biochem. Biophys. 1989; 270: 604–610
  • Del Corso A., Barsacchi D., Osman A. M., Mohamed A. S., Tozzi M. G., Camici M., Mura U. Lens aldo-keto reductase of Camelus dromedarius: Purification and properties. Biochim. Biophys. Acta 1989; 993: 116–120
  • O'Brien M. M., Schofield P. J. Polyol-pathway enzymes of human brain. Partial purification and properties of aldose reductase and hexonate dehydrogenase. Biochem. J. 1980; 187: 21–30
  • Flynn T. G. Aldehyde reductases: Monomeric NADPH-dependent oxidoreductases with multifunctional potential. Biochem. Pharmacol. 1982; 31: 2705–2712
  • Vander Jagt D. L., Stangebye L. A., Hunsaker L. A., Eaton R. P., Sibbit W. L., Jr. Purification of aldose reductase from human placenta and stabilization of the inhibitor binding site. Biochem. Pharmacol. 1988; 37: 1051–1056
  • von Wartburg J. P., Wermuth B. Aldehyde reductase from human tissues. Meth. Enzymol. 1982; 89: 506–513
  • Sawada H., Hara A., Kato F., Nakayama T. Purification and properties of reductases for aromatic aldehydes and ketones from guinea pig liver. J. Biochem. 1979; 86: 871–881
  • Felsted R. L., Gee M., Bachur N. R. Rat liver daunorubicin reductase, an aldo-keto reductase. J. Biol. Chem. 1974; 249: 3672–3679
  • McMahon R. E. Enzymatic Oxidation of alcohols, aldehydes and ketones. Handbook of Experimental Pharmacology, pt. 2, B. B. Brodie, J. Gillette. Springer-Verlag, New York 1971; vol. 28: 500–517
  • Bachur N. R. Cytoplasmic aldo-keto reductases: A class of drug-metabolizing enzymes. Science 1976; 193: 595–597
  • Lee V. H. L., Chien D. -S., Sasaki H. Ocular ketone reductase distribution and its role in the metabolism of ocularly applied levobunolol in the pigmented rabbit. J. Pharmacol. Exp. Then 1988; 246: 871–878
  • Woodward D. F., Novack G. D., Williams L. S., Nieves A. L., Potter D. E. Dihydrobunolol is a potent ocular beta-adrenoceptor antagonist. JOcular Pharmacol. 1987; 3: 11–15
  • Shimada S., Mishima H., Kitamura S., Tatsumi K. Nicotinamide N-oxide reductase activity in bovine and rabbit eyes. Invest. Ophthalmol. Vis. Sci. 1987; 28: 1204–1206
  • Shimada S., Mishima H., Nikaido H., Kitamura S., Tatsumi K. Reduction of drugs by ocular tissue preparations. Abstract I-404-P9, ISSX Meeting, KobeJapan, 1988
  • Shimada S., Mishima H. K., Nikaido H., Kitamura S., Tatsumi K. Purification of aldehyde oxidase from bovine ciliary body. Curr. Eye Res. 1989; 8: 721–726
  • Shimada S., Mishima H. K., Nikaido H., Kitamura S., Tatsumi K. Metabolism of drugs in the eye. Menadione-dependent reduction of tertiary amine JV-oxide by preparations from bovine ocular tissues. Curr. Eye Res. 1989; 8: 1309–1313
  • Shimada S., Mishima H., Kitamura S., Tatsumi K. Metabolism of drugs in the eye, Drug-reducing activity of preparations from bovine ciliary body. Curr. Eye Res. 1988; 7: 1069–1075
  • Yoshihara S., Tatsumi K. Guinea pig liver aldehyde oxidase as sulfoxide reductase: Its purification and characterization. Arch. Biochem. Biophys. 1985; 242: 213–224
  • Tatsumi K., Yamada H., Kitamura S. Reductive metabolism of A/-nitrosodiphenylamine to the corresponding hydrazine derivative. Arch. Biochem. Biophys. 1983; 226: 174–181
  • Sawada H., Hara A., Hayashibara M., Nakayama T. Guinea pig liver aromatic aldehyde-ketone reductases identical with 17B-hydroxysteroid dehydrogenase isozymes. JBiochem. 1979; 86: 883–892
  • Kitamura S., Tatsumi K. Azoreductase activity of liver aldehyde oxidase. Chem. Pharm. Bull. 1983; 31: 3334–3337
  • Tatsumi K., Kitamura S., Narai N. Reductive metabolism of aromatic nitro compounds including carcinogens by rabbit liver preparations. Cancer Res. 1986; 46: 1089–1093
  • Sugihara K., Tatsumi K. Participation of liver aldehyde oxidase in reductive metabolism of hydroxamic acids to amides. Arch. Biochem. Biophys. 1986; 247: 289–293
  • Shichi H., O'Meara R D. Purification and properties of anionic glutathione ^-transferase from bovine ciliary body. Biochem. J. 1986; 237: 365–371
  • Saneto R. R, Awasthi Y. C., Srivastava S. K. Glutathione S-transferases of the bovine retina. Biochem. J. 1982; 205: 213–217
  • Singh S. V., Dao D. D., Srivastava S. K., Awasthi Y. C. Purification and characterization of glutathione ^-transferases in human retina. Curr. Eye Res. 1984; 3: 1273–1280
  • Awasthi Y. C., Saneto R. P., Srivastava S. K. Purification and properties of bovine lens glutathione S-transferase. Exp. Eye Res. 1980; 30: 29–39
  • Saneto R. P., Awasthi Y. C., Srivastava S. K. Interrelationship between cationic and anionic forms of glutathione S-transferases of bovine ocular lens. Biochem. J. 1980; 191: 11–20
  • Singh S. V., Hong T. D., Srivastava S. K., Awasthi Y. C. Characterization of glutathione 5-transferases of human cornea. Exp. Eye Res. 1985; 40: 431–437
  • Das N. D., Shichi H. Gamma-glutamyl transpeptidase of bovine ciliary body: Purification and properties. Exp. Eye Res. 1979; 29: 109–121
  • Reddy V. N., Unakar N. J. Localization of gamma-glutamyl transpeptidase in rabbit lens, ciliary process and cornea. Exp. Eye Res. 1973; 17: 405–408
  • Ng M. C., Shichi H. Enzymes of mercapturate pathway in cultured bovine ciliary epithelial cells. J. Ocular Pharmacol. 1987; 3: 341–348
  • Kishida K., Akaki Y., Sasabe T., Yamamoto C., Manabe R. Glutathione conjugation of methazolamide and subsequent reactions in the ciliary body in vitro. J. Pharm. Sci. 1990; 79: 638–642
  • Hotta N., Kakuta H., Ando F., Sakamoto N. Current progress in clinical trials of aldose reductase inhibitors in Japan. Exp. Eye Res. 1990; 50: 625–628
  • Mizuno K. Studies on retinitis pigmentosa. Eye, Ear, Nose and Throat Monthly 1960; 39: 493–499
  • Putnam M. L., Schoenwald R. D., Duffel M. W., Bar-fknecht C. F., Segarra T. M., Campbell D. A. Ocular disposition of aminozolamide in the rabbit eye. Invest. Ophthalmol. Vis. Sci. 1987; 28: 1373–1382
  • Patil P. N., Trendelenburg U. The extraneuronal uptake and metabolism of 3H-isoprenaline in the rabbit iris. Naunyn-Schmiedeberg's Arch. Pharmacol. 1982; 318: 158–165
  • Jedziniak J. A., Kinoshita J. H. Activators and inhibitors of lens aldose reductase. Invest. Ophthalmol. 1971; 10: 357–366
  • Fukushi S., Merola S., Kinoshita J. H. Altering the course of cataracts in diabetic rats. Invest. Ophthalmol. Vis.5c J. 1980; 19: 313–315
  • Beyer-Mears A., Cruz E., Nicolas-Alexandre J., Varagiannis E. Sorbinil protection of lens components and cell hydration during diabetic cataract formation. Pharmacology 1982; 24: 193–200
  • Hu T. -S., Datiles M., Kinoshita J. H. Reversal of galactose cataract with sorbinil in rats. Invest. Ophthalmol. Vis. Sci. 1983; 24: 640–644
  • Jacobson M., Sharma Y. R., Cotlier E., Hollander J. D. Diabetic complications in lens and nerve and their prevention by sulin-dac or sorbinil: two novel aldose reductase inhibitors. Invest. Ophthalmol. Vis. Sci. 1983; 24: 1426–1429
  • Hu T. -S., Merola L. O., Kuwabara T., Kinoshita J. H. Prevention and reversal of galactose cataract in rats with topical sorbinil. Invest. Ophthalmol. Vis. Sci. 1984; 25: 603–605
  • Okuda J., Yashima K., Inagaki K., Miwa I. Effects of an aldose reductase inhibitor, l-[(p-bromophenyl)sulfonyl]hydantoin, on cataract formation and tissue polyol levels in galactosemic rats. Chem. Pharm. Bull. 1985; 33: 2990–2995
  • Beyer-Mears A., Cruz E. Reversal of diabetic cataract by sorbinil, an aldose reductase inhibitor. Diabetes 1985; 34: 15–21
  • Simard-Duquesne N., Greselin E., Gonzalez R., Dvornik D. Prevention of cataract development in severely galactosemic rats by the aldose reductase inhibitor, tolrestate (42048). Proc. Soc. Exp. Biol. Med. 1985; 178: 599–605
  • Unakar N., Tsui J., Johnson M. Aldose reductase inhibitors and prevention of galactose cataracts in rats. Invest. Ophthalmol. Vis. Sci. 1989; 30: 1623–1632
  • Lou M. F., Dickerson J. E., Jr., Handler M. L., Brazzell R. K., York B. M. The prevention of biochemical changes in lens, retina and nerve of galactosemic dogs by the aldose reductase inhibitor AL01576. J. Ocular Pharmacol. 1989; 5: 233–240
  • Varma S. D., Schocket S. S., Richards R. D. Implications of aldose reductase in cataracts in human diabetes. Invest. Ophthalmol. Vis. Sci. 1979; 18: 237–241
  • Crabbe M. J. C., Petchey M., Burgess S. E. P., Cheng H. The penetration of sorbinil, an aldose reductase inhibitor, into lens, aqueous humor and erythrocytes of patients undergoing cataract extraction. Exp. Eye Res. 1985; 40: 95–99
  • Kador P. F. Overview of the current attempts toward the medical treatment of cataract. Ophthalmology 1983; 90: 352–364
  • Hara A., Harado T., Kakagawa M., Matsuura M., Nakayama T., Sawada H. Isolation from the pig lens of two proteins with dihydrodiol dehydrogenase and aldehyde reductase activities. Bio-chem. J. 1989; 264: 403–407
  • Stribling D. Clinical trials with aldose reductase inhibitors. Exp. Eye Res. 1990; 50: 621–624
  • Cunha-Vaz J. G., Maurice D. M. The active transport of fluorescein by the retinal vessels and the retina. J. Physiol. 1967; 191: 467–486
  • Blair N. P., Zeimer R. C., Rusin M. M., Cunha-Vaz J. G. Outward transport of fluorescein from the vitreous in normal human subjects. Arch. Ophthalmol. 1983; 101: 1117–1121
  • Cole D. F. Aqueous and ciliary body. Biochemistry of the Eye, C. N. Graymore. Academic Press, London 1970; 105–181
  • Bito L. Z., Salvador E. V. Effects of anti-inflammatory agents and some other drugs on prostaglandin biotransport. J. Pharmacol. Exp. Ther. 1976; 198: 481–488
  • Bito L. Z. Absorptive transport of prostaglandins from intraocular fluids to blood: A review of recent findings. Exp. Eye Res. 1973; 16: 299–306
  • Bito L. Z., Wallenstein M. C. Transport of prostaglandins across the blood-brain and blood-aqueous barriers and the physiological significance of these absorptive transport processes. Exp. Eye Res. 1977; 25: 229–243, suppl.
  • Bito L. Z., Salvador E. V. Intraocular fluid dynamics. III. The site and mechanism of prostaglandin transfer across blood intraocular fluid barriers. Exp. Eye Res. 1972; 14: 233–241
  • Eakins K. E., Atwal M., Bhattacherjee P. Inactivation of prostaglandin E, by ocular tissues in vitro. Exp. Eye Res. 1974; 19: 141–146
  • Bito L. Z., Baroody R. Concentrative accumulation of 3H-prostaglandins by some rabbit tissues in vitro: The chemical nature of the accumulated 3H-labelled substances. Prostaglandins 1974; 7: 131–140
  • Bito L. Z. Prostaglandins and related compounds as potential ocular therapeutic agents. Biological Protection with Prostaglandins. CRC Press, Boca Raton, FL 1987; vol. 1: 231–252
  • Bito L. Z. Eicosanoid transport system: Mechanisms, Physiological roles, and inhibitors. CRC Handbook of Eicosanoids: Pros-taglandins and Related Lipids. CRC Press, Boca Raton, FL 1987; vol. 1: 211–231
  • Bito L. Z. Prostaglandins and other eicosanoids: Their ocular transport, pharmacokinetics, and therapeutic effects. Trans. Ophthalmol. Soc. UK 1986; 105: 162–170
  • Bito L. Z. Absorptive transport of prostaglandins and other eicosanoids across the blood-brain barrier system and its physiological significance. Blood-Brain Barrier in Health and Disease, M. Bradbury, M. G. Rumsby, A. J. Suckling. Ellis Horwood Ltd. 1985; 109–121
  • Maurice D. M. Drug exchanges between the blood and vitreous. The Blood-Retinal Barriers, J. G. Cunha-Vaz. Plenum Press. 1979; 165–178
  • Reddy V. N., Chakrapany B., Lim C. P. Blood-vitreous barrier to amino acids. Exp. Eye Res. 1977; 25: 543–554
  • Barza M., Kane A., Baum J. The effects of infection and probenecid on the transport of carbenicillin from the rabbit vitreous humor. Invest. Ophthalmol. Vis. Sci. 1982; 22: 720–726
  • Salminen L., Jarvinen H., Toivanen P. Distribution of tritiated benzylpenicillin in the rabbit eye. Invest. Ophthalmol. Vis. Sci. 1969; 47: 115–121
  • Faris B. M., Uwaydah M. W. Intraocular penetration of semisynthetic penicillins. Arch. Ophthalmol. 1974; 92: 501–505
  • Reddy V. N., Thompson M. R., Chakrapani B. Amino acid transport across blood-aqueous barrier of mammalian species. Exp. Eye Res. 1977; 25: 555–562
  • Furguiele F. P., Smith J. P., Baron J. G. Tobramycin levels in human eyes. Am. J. Ophthalmol. 1978; 85: 121–123
  • Oldendorf W. H. Lipid solubility and drug penetration of the blood-brain barrier. Proc. Soc. Exp. Biol. Med. 1974; 147: 813–816
  • Rapoport S. I., Ohno K., Pettigrew K. D. Drug entry into the brain. Brain Res. 1979; 172: 354–359
  • Levin V. A. Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J. Med. Chem. 1980; 23: 682–684
  • Cornford E. M., Braun L. D., Oldendorf W. H., Hill M. A. Comparison of lipid-mediated blood-brain penetrability in neonates and adults. Am. J. Physiol. 1982; 243: C161–C168
  • Reese T. S., Karnovsky M. J. Fine Structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol. 1967; 34: 207–217
  • Goldstein G. W., Betz A. L., Bowman P. D., Dorovini-Zis K. In vitro, studies of the blood-brain barrier using isolated brain capillaries and cultured endothelial cells. Ann. NY Acad. Sci. 1986; 481: 202–213
  • Bito L., Davson H., Levin E., Murray M., Snider N. The concentrations of free amino acids and other electrolytes in cerebrospinal fluid in vivo dialysate of brain, and blood plasma of the dog. J. Neurochem. 1966; 13: 1057–1057
  • Pollay M., Davson H. The passage of certain substances out of the cerebrospinal fluid. Brain 1963; 86: 137–150
  • Davson H., Kleeman C. R., Levin E. Quantitative studies of the passage of different substances out of the cerebrospinal fluid. J. Physiol. 1962; 161: 126–142
  • Pardridge W. M. Blood-brain barrier transport of nutrients. Fed. Proc 1986; 45: 2047–2049
  • Spector R. Micronutrient homeostasis in mammalian brain and cerebrospinal fluid. J. Neurochem. 1989; 53: 1667–1674
  • Oldendorf W. H. Brain uptake of radiolabeled amino acids, amines and hexoses after arterial injection. Am. J. Physiol. 1971; 221: 1629–1639
  • Oldendorf W. H., Szabo J. Amino acid assignment to one of three blood-brain barrier amino acid carriers. Am. J. Physiol. 1976; 230: 94–98
  • Pardridge W. M. Kinetics of competitive inhibition of neutral amino acid transport across the blood-brain barrier. J. Neurochem. 1977; 28: 103–108
  • Pardridge W. M., Oldendorf W. H. Kinetic analysis of blood-brain barrier transport of amino acids. Biochim. Biophys. Acta 1975; 401: 128–136
  • Pardridge W. M., Connor J. D. Saturable transport of amphetamine across the blood-brain barrier. Experientia 1973; 29: 302–304
  • Markovitz D. C., Fernstrom J. D. Diet and uptake of aldomet by the brain: Competition with natural large neutral amino acids. Sci-ence 1977; 197: 1014–1015
  • Greig N. H., Momma S., Sweeney D. J., Smith Q. R., Rapoport S. I. Facilitated transport of melphalan at the rat blood-brain barrier by the large neutral amino acid carrier system. Cancer Res. 1987; 47: 1571–1576
  • Cornford E. M., Braun L. D., Oldendorf W. H. Carrier mediated blood-brain barrier transport of choline and certain choline analogs. J. Neurochem. 1978; 30: 299–308
  • Greenwood J., Love E. R., Pratt O. E. Kinetics of thiamine transport across blood-brain barrier in the rat. J. Physiol. 1982; 327: 95–KB
  • Becker B. The transport of organic anions by the rabbit eye. I” In vitro iodopyracet (Diodrast) accumulation by ciliary body-iris preparations. Am. J. Ophthalmol. 1960; 50: 862–867
  • Forbes M., Becker B. The transport of organic anions by the rabbit eye. II”In vivo transport of iodopyracet (Diodrast). Am. J. Ophthalmol. 1960; 50: 867–873
  • Becker B. Cerebrospinal fluid iodide. Am. J. Physiol. 1961; 201: 1149–1151
  • Barany E. H. Inhibition by hippurate and probenecid of in vitro uptake of iodipamide and o-iodohippurate. A composite uptake system for iodipamide in choroid plexus, kidney cortex and anterior uvea of several species. Acta Physiol. Scand. 1972; 86: 12–27
  • Barany E. H. The liver-like anion transport system in rabbit kidney, uvea and choroid plexus. I. Selectivity of some inhibitors, direction of transport, possible physiological substrates. Acta Physiol. Scand. 1973; 88: 412–429
  • Barany E. H. The liver-like anoin transport system in rabbit kidney, uvea and choroid plexus. II. Efficiency of acidic drugs and other anions as inhibitors. Acta Physiol. Scand. 1973; 88: 491–504
  • Lorenzo A. V., Cutler R. W. P. Amino acid transport by choroid plexus in vitro. J. Neurochem. 1969; 16: 577–585
  • Coben L. A., Cotlier E., Beaty C., Becker B. Transport of amino acids by rabbit choroid plexus in vitro. Brain Res. 1971; 30: 67–82
  • Csaky T. Z., Rigor B. M., Sr. A concentrative mechanism for sugars in the choroid plexus. Life Sci. 1964; 3: 931–936
  • Spector R., Lorenzo A. V. Specificity of ascorbic acid transport system of the central nervous system. Am. J. Physiol. 1974; 226: 1468–1473
  • Berlin R. D., Purines. Active transport by isolated choroid plexus. Science 1969; 163: 1194–1195
  • Bdrany E. H. Organic cation uptake in vitro by the rabbit iris-ciliary body, renal cortex, and choroid plexus. Invest. Ophthalmol. 1976; 15: 341–349
  • Di Benedetto F. E., Bito L. Z. Transport of prostaglandins and other eicosanoids by the choroid plexus: Its characterization and physiological significance. J. Neurochem. 1986; 46: 1725–1731
  • Fishman R. A. Blood-brain and CSF barriers to penicillin and related organic acids. Arch. Neurol. 1966; 15: 113–124
  • Pappenheimer J. R., Heisey S. R., Jordan E. F. Active transport of diodrast and phenolsulfonphthalein from cerebrospinal fluid to blood. Am. J. Physiol. 1961; 200: 1–10
  • Cornford E. M., Diep C. P., Pardridge W. M. Blood-brain barrier transport of valproic acid. J. Neurochem 1985; 44: 1541–1550
  • Oldendorf W. H., Hyman S., Braun L., Oldendorf S. Z. Blood-brain barrier: Penetration of morphine, codeine, heroin, and methadone after carotid injection. Science 1972; 178: 984–986
  • Bito L. Z., Davson H., Hollingsworth J. R. Facilitated transport of prostaglandins across the blood-cerebrospinal fluid and blood-brain barriers. J. Physiol. 1976; 256: 273–285
  • Spector R., Goetzl E. J. Leukotriene C4 by the choroid plexus in vitro. Science 1985; 228: 325–327
  • Spector R., Goetzl E. J. Leukotriene C4 transport and metabolism in the central nervous system. J. Neurochem. 1986; 46: 1308–1312
  • Spector R., Lorenzo A. V. Folate transport by the choroid plexus in vitro. Science 1975; 187: 540–542
  • Cserr H. F., van Dyke D. H. 5-Hydroxyindoleacetic acid accumulation by isolated choroid plexus. Am. J. Physiol. 1971; 220: 718–723
  • Forn J. Active transport of 5-hydroxyindoleacetic acid by the rabbit choroid plexus in vitro. Biochem. Pharmacol. 1972; 21: 619–624
  • Meek J. L., Neff H. N. Acidic and neutral metabolites of norepinephrine: Their metabolism and transport from brain. J. Pharmacol. Exp. Ther. 1972; 181: 457–462
  • Hug C. C., Jr. Transport of narcotic analgesics by choroid plexus and kidney tissue in vitro. Biochem. Pharmacol. 1967; 16: 345–359
  • Wang J. H., Takemori A. E. Studies on the transport of morphine into the cerebrospinal fluid of rabbits. J. Pharmacol. Exp. Ther. 1972; 183: 41–48
  • Huang J. T., Takemori A. E. Accumulation of methadone by the choroid plexus in vitro. Neuropharmacol. 1975; 14: 214–246
  • Tochino Y., Schanker L. S. Active transport of quaternary ammonium compounds by the choroid plexus in vitro. Am. J. Physiol. 1965; 208: 666–673
  • Pritchard J. B. Accumulation of anionic pesticides by rabbit choroid plexus in vitro. J. Pharmacol. Exp. Ther. 1980; 212: 354–359
  • Kim C. S., O'Tuama L. A., Mann J. D., Roe C. R. Saturable accumulation of the anionic herbicide, 2, 4-dichlorophenoxyacetic acid (2,4-D) by rabbit choroid plexus: Early developmental origin and interaction with salicylates. J. Pharmacol. Exp. Ther. 1983; 225: 699–704
  • Suzuki H., Sawada Y., Sugiyama Y., Iga T., Hanano M. Transport of cimetidine by the rat choroid plexus in vitro. J. Pharmacol. Exp. Ther. 1986; 239: 927–935
  • Suzuki H., Sawada Y., Sugiyama Y., Iga T., Hanano M. Transport of benzylpenicillin by the rat choroid plexus in vitro. J. Pharmacol. Exp. Ther. 1987; 242: 660–665
  • Nohjoh T., Suzuki H., Sawada Y., Sugiyama Y., Iga T., Hanano M. Transport of cefodizime, a novel third-generation cephalosporin anitbiotic, in isolated rat choroid plexus. J. Pharmacol. Exp. Ther. 1989; 250: 324–328
  • Bigley R., Wirth M., Layman D., Stankova L. Interaction between glucose and dehydroascorbate transport in human neutrophils and fibroblasts. Diabetes 1983; 32: 545–548
  • Hjelle J. T., Baird-Lambert J., Cardinale G., Spector S., Udenfriend S. Isolated microvessels: The blood-brain barrier in vitro. Proc. Natl. Acad. Sci. USA 1978; 75: 4544–4548
  • Betz A. L., Goldstein G. W. Polarity of the blood-brain barrier: Neutral amino acid transport into isolated brain capillaries. Science 1978; 202: 225–226
  • Goldstein G. W., Wolinski J. S., Csejtey J., Diamond I. Isolation of metabolically active capillaries from rat brain. J. Neuro-chem. 1975; 25: 715–717
  • Goldstein G. W., Betz A. L., Bowman P. D. Use of isolated brain capillaries and cultured endothelial cells to study the blood-brain barrier. Fed. Proc 1984; 43: 191–195
  • van Bree J. B. M. M., DeBoer A. G., Danhof M., Ginsel L. A., Breimer D. D. Characterization of an “in vitro” blood-brain barrier: Effects of molecular size and lipophilicity on cerebrovascular endothelial transport rates of drugs. J. Pharmacol. Exp. Ther. 1988; 247: 1233–1239
  • De Bault L. E., Kahn L. E., Frommes S. P., Cancilla P. A. Cerebral microvessels and derived cells in tissue culture: Isolation and preliminary characterization. In Vitro 1979; 15: 473–487
  • Audus K. L., Borchardt R. T. Characteristics of the large neutral amino acid transport system of bovine microvessel endothelial cell monolayers. J. Neurochem. 1986; 47: 484–488
  • Bowman P. D., Betz A. L., Ar D., Wolinski J. S., Penney J. B., Shivers R. R., Goldstein G. W. Primary culture of capillary endothelium from rat brain. In Vitro 1981; 17: 353–362
  • Hargreaves K. M., Pardridge W. M. Neutral amino acid transport at the human blood-brain barrier. J. Biol. Chem. 1988; 263: 19392–19397
  • Kishi M., Ohkuma S., Kimori M., Kuriyama K. Characteristics of taurine transport system and its developmental pattern in mouse cerebral cortical neurons in primary culture. Biochim. Bio-phys. Acta 1988; 939: 615–623
  • Tayarani I., Cloez I., Lefauconnier J. -M., Bourre J. -M. Sodium-dependent high-affinity uptake of taurine by isolated rat brain capillaries. Biochim. Biophys. Acta 1989; 985: 168–172
  • van Bree J. B. M. M., Audus K. L., Borchardt R. T. Carrier-mediated transport of baclofen across monolayers of bovine brain endothelial cells in primary culture. Pharmaceut. Res. 1988; 5: 369–371
  • Wu P. H., Phillis J. W. Uptake of adenosine by isolated rat brain capillaries. J. Neurochem. 1982; 38: 687–690
  • Ghersi-Egea J. -F., Minn A., Siest G. A new aspect of the protective functions of the blood-brain barrier: Activities of four drug-metabolizing enzymes in isolated rat brain microvessels. Life Sci. 1988; 42: 2515–2523
  • Baranczyk-Kuzma A., Audus K. L., Borchardt R. T. Catecholamine-metabolizing enzymes of bovine brain microvessel endothelial cell monolayers. J. Neurochem. 1986; 46: 1956–1960
  • Deuticke B. Monocarboxylate transport in red blood cells: Kinetics and chemical modification. Meth. Enzymol. 1989; 173: 732–745
  • Kaplan R. S., Pratt R. D., Pedersen P. L. Purification and re-constitution of the phosphate transporter from rat liver. Meth. Enzymol. 1989; 173: 732–745
  • Goldinger J. M., Khalsa B. D. S., Hong S. K. Photoaffinity labeling of organic anion transport system in proximal tubule. Am. J. Physiol. 1984; 247: C217–C227
  • Wolkoff A. W., Chung C. T. Identification, purification and partial characterization of an organic anion binding protein from rat liver cell plasma membrane. J. Clin. Invest. 1980; 65: 1152–1161
  • Stremmel W., Gerber M. A., Glezerov V., Thung S. N., Kochwa S., Berk P. D. Physiocochemical and immunohistologi-cal studies of a sulfobromophthalein-and bilirubin-binding protein from rat liver plasma membranes. J. Clin. Invest. 1983; 71: 1796–1805
  • Reichen J., Berk P. D. Isolation of an organic anion binding protein from rat liver plasma membrane fraction by affinity chromatography. Biochem. Biophys. Res. Commun. 1979; 91: 484–489
  • Dick A. P. K., Harik S. I., Klip A., Walker D. M. Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity. Proc. Natl. Acad. Sci. USA 1984; 81: 7233–7237
  • Baldwin S. A., Cairns M. T., Gardiner R. M., Ruggier R. A D-glucose-sensitive cytochalasin B binding component of cerebral microvessels. J. Neurochem. 1985; 45: 650–652
  • Suleiman S. A., Spector R. Purification and characterization of a folate binding protein from porcine choroid plexus. Arch. Biochem. Biophys. 1981; 208: 87–94
  • Loscher W., Nau H. Distribution of valproic acid and its metabolites in various brain areas of dogs and rats and after acute and prolonged treatment. J. Pharmacol. Exp. Then 1983; 226: 845–854
  • Neff N., Rossi G. V., Chase G. D., Rabinowitz J. L. Distribution and metabolism of mescaline-C14 in the cat brain. J. Pharmacol. Exp. Ther. 1964; 144: 1–7
  • Snyder S. H., Reivich M. Regional localization of lysergic acid diethylamide in monkey brain. Nature 1966; 209: 1093–1095
  • Martin B. R., Dewey W. L., Harris L. S., Beckner J. S. 3H-A9-tetrahydrocannabinol tissue and subcellular distribution in the CNS and tissue distribution in peripheral organs of tolerant and non-tolerant dogs. J. Pharmacol. Exp. Ther. 1976; 196: 128–144
  • Sershen H., Reith M. E. A., Hashim A., Lajtha A. Comparison of [3H]nicotine and [3H]acetylcholine binding in mouse brain: Regional distribution. Res. Commun. Chem. Pathol. Pharmacol. 1985; 48: 345–352
  • Mohler H., Okada T., Heitz P., Ulrich J. Biochemical identification of the site of action of benzodiazepines in human brain by 3H-diazepam binding. Life Sci. 1978; 22: 985–996
  • Young W. S.HI, Kuhar M. J. Radiochemical localization of benzodiazepine receptors in rat brain. J. Pharmacol. Exp. Ther. 1980; 212: 337–346
  • Kim C., Speisky M. B., Kalant H. Simultaneous determination of biogenic amines and morphine in discrete rat brain regions by high performance liquid chromatography with electrochemical detection. J. Chromatog. 1986; 370: 303–313
  • Agnew W. F., Rumbaugh C. L., Cheng J. T. The uptake of A9-tetrahydrocannabinol in choroid plexus and brain cortex in vitro and in vivo. Brain Res. 1976; 109: 355–366
  • Shah N. S., Powell D. A., Shahi A. B., Wiscovitch R., McAmis W. Distribution of 3H-levo-cocaine in brain regions of rabbit after intracerebroventricular administration. Res. Commun. Subst. Abuse 1982; 3: 433–441
  • Minder R., Schnetzer F., Bickel M. H. Hepatic and extrahepatic metabolism of the psychotropic drugs, chlorpromazine, imipramine and imipramine N-oxide. Naunyn-Schmiedebergs Arch. Pharmakol. 1971; 268: 334–347
  • Dingell J. V., Sulser F., Gillette J. R. Species differences in the metabolism of imipramine and desmethylimipramine. J. Pharmacol. Exp. Ther. 1964; 143: 14–22
  • Machinist J. M., Dehner E. W., Ziegler D. M. Microsomal oxidases. III. Comparison of species and organ distribution of dialky-larylamine N-oxide dealkylase and dialkylarylamine JV-oxidase. Arch. Biochem. Biophys. 1968; 125: 858–864
  • Uehleke H. Extrahepatic microsomal drug metabolism. Proc. Eur. Soc. Study Drug Toxicity 1969; 10: 94–100
  • Volk B., Amelizad Z., Anagnostopoulos J., Knoth R., Oesch F. First evidence of cytochrome P-450 induction in the mouse brain by phenytoin. Neurosci. Lett. 1988; 84: 219–224
  • Marietta M. P., Vesell E. S., Hartmann R. D., Weisz J., Dvorchik B. H. Characterization of cytochrome P-450 dependent aminopy-rine N-demethylation in rat brain: Comparison with hepatic aminopy-rine N-demethylation. J. Pharmacol. Exp. Then 1979; 208: 271–279
  • Shiverick K. T., Notelovitz M. Mestranol-induced hypertension: Characterization of cytochrome P-450 dependent catechol estrogen formation in brain microsomes. Biochem. Pharmacol. 1983; 32: 101–106
  • Sasame H. A., Ames M. M., Nelson S. D. Cytochrome P-450 and NADPH cytochrome c reductase in rat brain: Formation of catechols and reactive catechol metabolites. Biochem. Biophys. Res. Commun. 1977; 78: 919–926
  • Cohn J. A., Alvares A. P., Kappas A. On the occurrence of cytochrome P-450 and aryl hydrocarbon hydroxylase activity in rat brain. JExp. Med. 1977; 145: 1607–1611
  • Walther B., Ghersi-Egea J. F., Minn A., Siest G. Subcellular distribution of cytochrome P-450 in the brain. Brain Res. 1986; 375: 338–344
  • Warner M., Kohler C., Hansson T., Gustafson J. -A. Regional distribution of cytochrome P-450 in the rat brain: Spectral quantitation and contribution of P-450b,e and P-450c,d. J. Neurochem. 1988; 50: 1057–1064
  • Paul S. M., Axelrod J., Diliberto E. J., Jr. Catechol estrogen-forming enzyme of brain: Demonstration of a cytochrome P-450 monooxygenase. Endocrinology 1977; 101: 1604–1610
  • Mesnil M., Testa B., Jenner P. Aryl hydrocarbon hydroxylase in rat brain microsomes. Biochem. Pharmacol. 1985; 34: 435–436
  • Srivastava S. P., Seth P. K. 7-Ethoxycoumarin 0-deethylase activity in rat brain microsomes. Biochem. Pharmacol. 1983; 32: 3657–3660
  • Ghersi-Egea J. F., Walther B., Perrin R., Minn A., Siest G. Inducibility of rat brain drug-metabolizing enzymes. Eur. J. Drug Metabol. Pharmacokin. 1987; 12: 263–265
  • Rouet P., Alexandrov K., Markovits P., Frayssinet C., Dansette P. M. Metabolism of benzo[a]pyrene by brain microsomes of fetal and adult rats and mice. Induction by 5,6-benzoflavone, comparison with liver and lung microsomal activities. Carcinogenesis 1981; 2: 919–926
  • Das M., Seth P. K., Mukhtar H. Characterization of microsomal aryl hydrocarbon hydroxylase of rat brain. J. Pharmacol. Exp. Then 1981; 216: 156–161
  • Das M., Seth P. K., Mukhtar H. NADH-dependent inducible aryl hydrocarbon hydroxylase activity in rat brain mitochondria. Drug Metab. Dispos. 1971; 9: 69–70
  • Das M., Seth P. K., Dixit R., Mukhtar H. Aryl hydrocarbon hydroxylase of rat brain mitochondria: Properties of, and effect of inhibitors and inducers on, enzyme activity. Arch. Biochem. Bio-phys. 1982; 217: 205–215
  • Oesch F., Glatt H., Schmassmann H. The apparent ubiquity of epoxide hydratase in rat organs. Biochem. Pharmacol. 1977; 26: 603–607
  • Walther B., Ghersi-Egea J. -F., Jayyosi Z., Minn A, Siest G. Ethoxyresorufin O-deethylase activity in rat brain subcellular fractions. Neuroscience Lett. 1987; 76: 58–62
  • Kodeira H., Spector S. Transformation of thebaine to ori-pavine, codeine, and morphine by rat liver, kidney, and brain microsomes. Proc. Natl. Acad. Sci. USA 1988; 85: 1267–1271
  • Benuck M., Reith M. E. A., Shershen H., Wiener H. L., Lajtha A. Oxidative metabolism of cocaine: Comparison of brain and liver. Proc. Soc. Exp. Biol. Med. 1989; 190: 7–13
  • Watanabe K., Tanaka T., Yamamoto I., Yoshimura H. Brain microsomal oxidation of A8-and A9-tetrahydrocannabinol. Biochem. Biophys. Res. Commun. 1988; 157: 75–80
  • Christensen H. D., Freudenthal R. I., Gidlay J. T., Rosenfeld R., Boegli G., Testino L., Brine D. R., Pitt C. G., Wall M. E. Activity of A8-and A9-tetrahydrocannabinol and related compounds in the mouse. Science 1971; 172: 165–167
  • Yamamoto I., Narimatsu S., Watanabe K., Shimonishi T., Yoshimura H., Nagano T. Human liver microsomal oxidation of A8-tetrahydrocannabinol. Chem. Pharm. Bull. 1983; 31: 1784–1787
  • Quato M. K., Maines M. D. Regulation of heme and drug metabolism activities in the brain by manganese. Biochem. Biophys. Res. Commun. 1985; 128: 18–24
  • Chen Z. R., Irvine R. J., Bochner F., Somogyi A. A. Morphine formation from codeine in rat brain: A possible mechanism of codeine analgesia. Life Sci. 1990; 46: 1067–1074
  • Masana M., de Toranzo E. G. D., Castro J. A. Studies on ni-furtimox nitroreductase activity in liver and other rat tissues. Arch. Int. Pharmacodyn 1984; 270: 4–10
  • Kochli H. W., Wermuth B., von Wartburg J. -P. Characterization of a mitochondrial NADH-dependent nitro reductase from rat brain. Biochim. Biophys. Acta 1980; 616: 133–142
  • Hook G. E. R., Haseman J. K., Lucier G. W. Induction and suppression of hepatic and extrahepatic foreign-compound metabolizing enzyme systems by 2,3,7,8-tetrachlorodibenzo-/?-dioxin. Chem.-Biol. Interact. 1975; 10: 199–214
  • White H. L., Wu J. C. Multiple binding sites of human brain monoamine oxidase as indicated by substrate competition. J. Neu-rochem 1975; 25: 21–26
  • Gabay S., Achee F. M., Mentes G. Some parameters affecting the activity of monoamine oxidase in purified bovine brain mitochondria. J. Neurochem. 1976; 27: 415–424
  • Schuur A., Ho B. T., Schoolar J. C. Human brain monoamine oxidase: One molecular entity–multiple binding sites. J. Pharm. Pharmacol. 1981; 33: 165–170
  • Sitaram B. R., Talomsin R., Blackman G. L., McLeod W. R. Study of metabolism of psychotomimetic indolealkylamines by rat tissue extracts using liquid chromatography. Biochem. Pharmacol. 1987; 36: 1503–1508
  • Barker S. A., Monti J. A., Christian S. T. Metabolism of the hallucinogen iV.iV-dimethyltryptamine in rat brain homogenates. Biochem. Pharmacol. 1980; 29: 1049–1057
  • Chemnitius J. M., Zech R. Carboxylesterases in primate brain: Characterization of multiple forms. Int. J. Biochem. 1983; 15: 1019–1025
  • Hj Oring N., Svensmark O. Carboxylesterases of human brain extract. Purification and properties of a butyrylesterase. Biochim. Bio-phys. Acta 1977; 481: 500–514
  • Dabich D., Chakrapani B., Syner F. N. Purification and properties of esterases characteristic of adult rat brain. Biochem. J. 1968; 110: 713–718
  • Selfe S., Storm D. R. Deacetylation of forskolin catalyzed by bovine brain membranes. Biochem. Biophys. Res. Commun. 1985; 133: 52–59
  • Bhat S. V., Bajwa B. S., Dornauer M., de Souza N. J. Structures and stereochemistry of new labdane diterpenoids from Coleus forskohlii Briq. Tetrahedron Lett. 1977; 19: 1669–1672
  • Way E. L., Young J. M., Kemp J. W. Metabolism of heroin and its pharmacologic implications. Bull. Narc 1965; 17: 25–33
  • Maksay G., Kardos J., Simonyi M., Tegyey Zs., Otvos L. Specific binding of racemic oxazepam to rat brain synaptosomes. Arzne-imittelforsch.lDrug Res. 1981; 31: 979–981
  • Oomen A., George S. T., Balasubramanian A. S. Phenacetin iV-deacetylase and its nonidentity with the serotonin-sensitive aryl acylamidase of brain. Life Sci. 1980; 26: 2129–2136
  • Oomen A., Balasubramanian A. S. The association of serotonin-sensitive aryl acylamidase with acetylcholinesterase in the monkey brain. Eur. J. Biochem. 1979; 94: 135–143
  • George S. T., Balasubramanian A. S. The identity of the serotonin-sensitive aryl acylamidase with acetylcholinesterase from human erythrocytes, sheep basal ganglia and electric eel. Eur J. Biochem. 1980; HI: 511–524
  • Moore D. E., Hess G. P. Acetylcholinesterase-catalyzed hydrolysis of an amide. Biochemistry 1975; 14: 2386–2389
  • Hsu L. L., Halaris A. E., Freedman D. X. Rat brain aryl acylamidase: Further characterization of multiple forms. Int. J. Biochem. 1982; 14: 581–584
  • Fujimoto D. Serotonin-sensitive aryl acylamidase in rat brain. Biochem. Biophys. Res. Commun. 1974; 61: 12–14
  • Ramsay R. B., Smith K. R., Jr., Crafts D. C., Chung H. D., Fredericks M. Hydrolytic enzyme activities of the nervous system. Arch. Neurol. 1980; 37: 356–359
  • Alvares K., Balasubramanian A. S. Lysosomal and microsomal B-glucuronidase of monkey brain. Differential elution characteristics from Con A-sepharose and neutral sugar composition. Biochim. Bio-phys. Acta 1982; 708: 124–133
  • Stevens R. L., Fluharty A. L., Killgrove A. R., Kihara H. Ar-ylsulfatase of human tissue. Studies on a form of arylsulfatase B found predominantly in brain. Biochim. Biophys. Acta 1977; 481: 549–560
  • Mathew J., Balasubramanian A. S. ArySulphatase C and estrone sulphatase of sheep hypothalamus, preoptic area, and midbrain: Separation of hydrophobic interaction chromatography and evidence for differences in their lipid environment. J. Neurochem. 1982; 39: 1205–1209
  • Balasubramanian K. A., Bachhawat B. K. Purification, properties and glycoprotein nature of arylsulfatase A from sheep brain. Biochim. Biophys. Acta 1975; 403: 113–121
  • Iwamori M., Moser H. W., Kishimoto Y. Steroid sulfatase in brain: Comparison of sulfohydrolase activities for various steroid sulfates in normal and pathological brains, including the various forms of metachromatic leukodystrophy. J. Neurochem. 1976; 27: 1389–1395
  • Eto Y., Rampini S., Wiesmann U., Herschkovitz N. N. Enzy-mic studies of sulphatases in tissues of the normal human and in metachromatic leukodystrophy with multiple sulphatase deficiences: Arylsulphatases A, B, and C, cerebroside sulphatase, psychosine sulphatase and steroid sulphatases. J. Neurochem 1974; 23: 1161–1170
  • Lakshmi S., Balasubramanian A. S. The distribution of estrone sulphatase, dehydroepiandrosterone sulphatase, and arylsulphatase C in the primate (Macaca radiata) brain and pituitary. J. Neurochem. 1981; 37: 358–362
  • Perumal A. S., Robins E. Regional and subcellular distribution of aryl-and steroid sulfatases in brain. Brain Res. 1973; 59: 349–358
  • Knapstein P., David A., Wu C. H., Archer D. F., Flickinger G. L., Touchstone J. C. Metabolism of free and sulfoconjugated DHEA in brain tissue in vivo and in vitro. Steroids 1968; 11: 885–896
  • Hobkirk R. Steroid sulfotransferases and steroid sulfatases: Characteristics and biological roles. Can. J. Biochem. Cell Biol. 1985; 63: 1127–1144
  • Cash C. D., Maitre M., Rumigny J. F., Weissman-Nanopoulos D., Mandel P. Succinate semialdehyde reductases and their product: 4-hydroxybutyrate. Enzymology ofCarbonyl Metabolism: Aldehyde Dehydrogenase and Aldo/Keto Reductase, H. Weiner, B. Wermuth. Alan Liss, New York 1982; 379–395
  • Wermuth B., Burgisser H., Bohren K., von Wartburg J. P. Purification and characterization of human brain aldose reductase. Eur. J. Biochem. 1982; 127: 279–284
  • Boghosian R. A., McGuinness E. T. Affinity purification and properties of porcine brain aldose reductase. Biochim. Biophys. Acta 1979; 567: 278–286
  • Wermuth B. Purification and properties of an NADPH-dependent carbonyl reductase from human brain. J. Biol. Chem. 1981; 256: 1206–1213
  • O'Brien M. M., Schofield R J. Polyol-pathway enzymes of human brain. Partial purification and properties of aldose reductase and hexonate dehydrogenase. Biochem. J. 1980; 187: 21–30
  • Hoffman P. L., Wermuth B., von Wartburg J. -P. Multiple aldehyde reductases of human brain. Adv. Exp. Med. Biol. 1980; 132: 749–759
  • Ris M. M., von Wartburg J. -P. Heterogeneity of NADPH-dependent aldehyde reductase from human and rat brain. Eur. J. Biochem. 1973; 37: 69–77
  • Ryle C. M., Tipton K. E. Subcellular localization of aldehyde reductase activities in ox brain. Biochem. J. 1981; 197: 715–720
  • Rivett A. J., Smith I. L., Tipton K. F. The enzymes catalysing succinic semialdehyde reduction in rat brain. Biochem. Pharmacol. 1981; 30: 741–747
  • Tabakoff B., Anderson R., Alivisatos S. G. A. Enzymatic reduction of “biogenic” aldehydes in brain. Mol. Pharmacol. 1973; 9: 428–437
  • Wermuth B. Human carbonyl reductases. Enzymology of Carbonyl Metabolism: Aldehyde Dehydrogenase and Aldo/Keto Reductase, H. Weiner, B. Wermuth. Alan Liss, New York 1982; 261–274
  • Bohren K. M., von Wartburg J. -P., Wermuth B. Kinetics of carbonyl reductase from human brain. Biochem. J. 1987; 244: 165–171
  • Hoffman P. L., Wermuth B., von Wartburg J. P. Human brain aldehyde reductases: Relationship to succinic semialdehyde reductase and aldose reductase. J. Neurochem. 1980; 35: 354–366
  • Enzyme Nomenclature, Recommendations (1984)) of the Committee of the International Union of Biochemists. Academic Press, New York 1984
  • Turner A. J. Aldehyde reductases: Enzymes in search of a function. Enzymology of Carbonyl Metabolism: Aldehyde Dehydrogenase and AldolKeto Reductase, H. Weiner, B. Wermuth. Alan Liss, New York 1982; 183–195
  • Monder C., Bradlow H. L. Cortoic acids: Explorations at the frontier of corticosteroid metabolism. Recent Progr. Hormone Res. 1980; 36: 345–400
  • Lipman V., Monder C. Purification and properties of an NADPH-dependent 21-oxo-20-hydroxysteroid reductase (170-aldol reducatase) from sheep liver. JBiol. Chem. 1978; 253: 2126–2131
  • Turner A. J., Tipton K. F. The characterization of two reduced nicotinamide-adenine dinucleotide phosphate-linked aldehyde reductases from pig brain. Biochem. J. 1972; 130: 765–772
  • Matsuda Y. M., Hoshino H. Conversion in vivo of succinic semi-aldehyde to 4-hydroxybutyrate in the mouse. Jikeikai Med. J. 1976; 23: 189, as cited by Cash et al. [412]
  • Turner A. J., Flynn T. G. The nomenclature of aldehyde reductases. Enzymology of Carbonyl Metabolism: Aldehyde Dehydrogenase and AldolKeto Reductase, H. Weiner, B. Wermuth. Alan Liss, New York 1982; 401–402
  • Flynn T. G. Aldehyde reductases: Monomeric NADPH-dependent oxidoreductases with multifunctional potential. Biochem. Pharmacol. 1982; 31: 2705–2712
  • Agarwal D. P, Hafer G., Harada S., Goedde H. W. Studies on aldehyde dehydrogenase and aldehyde reductase in human brain. Enzymology of Carbonyl Metabolism: Aldehyde Dehydrogenase and AldolKeto Reductase, H. Weiner, B. Wermuth. Alan Liss, New York 1982; 319–327
  • Harada S., Agarwal D. P., Goedde H. W. Human aldehyde dehydrogenase: 3,4-dihydroxyphenylaldehyde metabolizing enzymes. Enzymology of Carbonyl Metabolism: Aldehyde Dehydrogenase and AldolKeto Reductase, H. Weiner, B. Wermuth. Alan Liss, New York 1982; 147–153
  • Aitio A. UDP glucuronosyltransferase activity in various rat tissues. Int. J. Biochem. 1974; 5: 325–330
  • Ghersi-Egea J. F., Walther B., Decolin D., Minn A., Siest G. The activity of 1-naphthol-UDP-glucuronosyltransferase in the brain. Neuropharmacology 1987; 26: 367–372
  • Shigezane J., Oguri K., Mishima M., Yoshimura H. UDP-glu-curonyltransferases in mice brain and the inducibility. J. Pharmaco-Dyn. 1982; 5: S–61
  • Ghersi-Egea J. F., Tayarani Y., Lefauconnier J. M., Minn A. Enzymatic protection of the brain: Role of 1-naphthol UDP-glucu-ronosyltransferase from cerebral tissue and cerebral microvessels. Cell. Molec. Aspects of Glucuronidation, G. Siest, J. Magdalou, B. Burchell. Colloque INSERM/John Libbey Eurotext Ltd. 1988; 173: 169–175
  • Wahlstrom A., Hammar L., Lundin L. -G., Rane A. Morphine metabolism in mouse brain. Natl. Inst. Drug Abuse Res. Monogr. Sen 1986; 75: 603–606
  • Renskers K. J., Feor K. D., Roth J. A. Sulfation of dopamine and other biogenic amines by human phenol sulfotransferase. J. Neu-rochem. 1980; 34: 1362–1368
  • Giorgi O., Meek J. L. Sulfation of peptides and simple phenols by rat brain phenolsulfotransferase. Inhibition by dichloronitrophe-nol. Biochem. Pharmacol. 1985; 34: 45–49
  • Young W. F., Jr., Laws E. R., Jr., Scarbrough F. W., Weinshilboum R. M. Human phenol sulfotransferase: Correlation of brain and platelet activities. JNeurochem. 1985; 44: 1131–1137
  • Weinshilboum R. M. Phenol sulfotransferase in humans: Properties, regulation, and function. Fed. Proc 1986; 45: 2223–2228
  • Wong K. P. The biosynthesis of 3-methoxy-4-hydroxyphenylgIycol sulphate by liver and brain. J. Neurochem. 1975; 24: 1059–1063
  • Pennings E. J. M., Vrielink R., van Kempen G. M. J. Kinetics and mechanism of the rat brain phenol sulphotransferase reaction. Biochem. J. 1978; 173: 299–307
  • Pennings E. J. M., Vrielink R., Wolters W. L., van Kempen G. M. J. Inhibition of rat brain phenol sulphotransferase in vitro by noradrenaline and dopamine metabolites. J. Neurochem. 1976; 27: 915–920
  • Rein G., Glover V., Sandler M. Characterization of human brain phenolsulfotransferase. J. Neurochem. 1984; 42: 80–85
  • Rein G., Glover V., Sandler M. Multiple forms of phenolsul-photransferase in human tissues. Selective inhibition by dichloroni-trophenol. Biochem. Pharmacol. 1982; 31: 1893–1897
  • Foldes A., Meek J. L. Rat brain phenolsulfotransferase–partial purification and some properties. Biochim. Biophys. Acta 1973; 327: 365–374
  • Young W. F., Jr., Okazaki H., Laws E. R., Jr., Weinshilboum R. M. Human brain phenol sulfotransferase: Biochemical properties and regional localization. J. Neurochem. 1984; 43: 706–715
  • Jenner W. N., Rose F. A. Studies on the sulphation of 3,4-dihydroxyphenylethylamine (dopamine) and related compounds by rat tissues. Biochem. J. 1973; 135: 109–114
  • Karoum F., Moyer-Schwing J., Potkin S. G., Wyatt R. J. Presence of free, sulfate and glucuronide conjugated 3-methoxy-4-hydroxyphenylglycol in human brain, cerebrospinal fluid and plasma. Brain Res. 1977; 125: 333–339
  • Schanberg S. M., Schildkraut J. J., Breese G. R., Kopin I. J. Metabolism of normetanephrine-3H in rat brain–identification of conjugated 3-methoxy-4-hydroxyphenylglycol as the major metabolite. Biochem. Pharmacol. 1968; 17: 247–254
  • Tyce G. M., Messick J. M., Yaksh T. L., Byer D. E. V., Danielson D. R., Rorie D. K. Amine sulfate formation in the central nervous system. Fed. Proc 1986; 45: 2247–2253
  • Borchardt R. T., Cheng C. F. Purification and characterization of rat heart and brain catechol methyltransferase. Biochim. Bio-phys. Acta 1978; 522: 49–62
  • White H. L., Wu J. C. Properties of catechol 0-methyl-transferases from brain and liver of rat and human. Biochem. J. 1975; 145: 135–143
  • Boppana V. K., Dolce K. M., Cyronak M. J., Ziemniak J. A. Simplified procedures for the determination of fenoldopam and its metabolites in human plasma by high-performance liquid chromatography with electrochemical detection: Comparison of manual and robotic preparation methods. J. Chromatogr. 1989; 487: 385–399
  • Burba J. V., Becking G. C. Effect of the antioxidant nordihy-droguaiaretic acid on the in vitro activity of catechol-O-methyl-transferase. Arch. Int. Pharmacodyn. 1969; 180: 323–330
  • Gordonsmith R. H., Raxworthy M. J., Gulliver P. A. Substrate stereospecificity and selectivity of catechol-0-methyltransferase for dopa, dopa derivatives and a-substituted catecholamines. Biochem. Pharmacol. 1982; 31: 433–437
  • Hagan R. M., Raxworthy M. J., Gulliver P. A. Benserazide and carbidopa as substrates of catechol-O-methyltransferase: New mechanism of action in Parkinson's disease. Biochem. Pharmacol. 1980; 29: 3123–3126
  • Hsu L. L., Geyer M. A., Mandell A. J. Extrapineal amine N-acetylation in rat brain. Biochem. Pharmacol. 1976; 25: 815–819
  • Yang H. -Y.T., Neff N. H. Brain N-acetyltransferase: Substrate specificity, distribution and comparison with enzyme activity from other tissues. Neuropharmacology 1976; 15: 561–564
  • Voisin P., Namboodiri M. A. A., Klein D. C. Arylamine N-acetyltransferase and arylalkylamine N-acetyltransferase in the mammalian pineal gland. J. Biol. Chem. 1984; 259: 10913–10918
  • Paul S. M., Hus L. L., Mandell A. J. Extrapineal N-acetyltransferase activity in rat brain. Life Sci. 1975; 15: 2135–2143
  • Chasseaud L. F. The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents. Adv. Cancer Res. 1979; 29: 175–274
  • Das M., Mukhtar H., Seth P. K. Effect of acrylamide on brain and hepatic mixed-function oxidases and gluthathione 5-transferase in rats. Toxicol. Appl. Pharmacol. 1982; 66: 420–426
  • Di Ilio C., Polidoro G., Arduini A., Federici G. Glutathione 5-transferase activity from guinea-pig brain: A comparison with hepatic multiple forms. Gen. Pharmacol. 1982; 13: 485–490
  • Kubota T., Miyaura S., Isono H. Rat brain glutathione 5-transferases. Chem. Pharm. Bull. 1985; 33: 5399–5403
  • Dierickx P. J. Soluble glutathione 5-transferase isoenzymes in rat brain. Toxicology Lett. 1983; 18: 121–125
  • Asaoka K., Takahashi K. Purification and properties of porcine brain glutathione 5-transferases. J. Biochem. 1983; 94: 1191–1199
  • Young P. R., Briedis A. V. Purification and kinetic mechanism of the major glutathione 5-transferase from bovine brain. Biochem. J. 1989; 257: 541–548
  • Ogorochi T., Ujihara M., Narumiya S. Purification and properties of prostaglandin H-E isomerase from the cytosol of human brain: Identification as anionic forms of glutathione 5-transferase. J. Neuro-chem. 1987; 48: 900–909
  • Das M., Mukhtar H., Seth P. K. Aryl hydrocarbon hydroxylase and glutathione-5-transferase activities in discrete regions of rat brain. Toxicol. Lett. 1982; 13: 125–128
  • Das M., Dixit R., Seth P. K., Mukhtar H. Glutathione 5-transferase activity in the brain: Species, sex, regional and age differences. J. Neurochem. 1981; 36: 1439–1442
  • Dixit R., Mukhtar H., Seth P. K., Krishna Murti C. R. Conjugation of acrylamide with glutathione catalysed by glutathiones-transferase of rat liver and brain. Biochem. Pharmacol. 1981; 30: 1739–1744
  • Dixit R., Seth P. K., Mukhtar H. Brain glutathiones-transferase catalyzed conjugation of acrylamide: A novel mechanism for detoxification of neurotoxin. Biochem. Int. 1980; 1: 547–552
  • Abramovitz M., Homma H., Ishigaki S., Tansey F., Cammer W., Listowsky I. Characterization and localization of glutathione-5-transferases in rat brain and binding of hormones, neurotransmitters, and drugs. J. Neurochem. 1988; 50: 50–57
  • Olsson M., Guthenberg C., Mannervik B. Glutathione transferase in human brain. Extrahepatic Drug Metabolism and Chemical Carcinogenesis, J. Rydstrom, J. Montelius, M. Bengtsson. Elsevier Science Publishers. 1983; 191–192
  • Hopewell J. W., Wright E. A. The importance of implantation site in cerebral carcinogenesis. Cancer Res. 1969; 29: 1927–1931
  • Markovits P., Le S. Vy, Nocentini S., Mazabraud A., Velizarov A., Sabharwal P. S., Benda P. Transformation maligne in vitro de cellules de cerveau foetal de hamster par le benzo(a)pyrene. Compt. Rend. Acad. Sci. Paris 1976; 282: 2015–2020
  • Rice J. M., Joshi S. R., Shenefelt R. E., Wenk M. L. Transplacental carcinogenic activity of 7,12-dimethylbenz[a]anthracene. Carcinogenesis 1978; 3: 413–422
  • Juchau M. R., Di Giovanni J., Namkung M. J., Jones A. H. A comparison of the capacity of fetal and adult liver, lung, and brain to convert polycyclic aromatic hydrocarbons to mutagenic and cytotoxic metabolites in mice and rats. Toxicol. Appl. Pharmacol. 1979; 49: 171–178
  • Langston J. W., Ballard P., Tetrud J. W., Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219: 979–980
  • Forno L. S. Pathology of Parkinson's disease. Movement Disorders, C. D. Marsden, S. Fahn. Butterworth Scientific, London 1982; 25–40
  • Burns R. S., Chieuh C. C., Markey S. P., Ebert M. H., Jaco-bowitz D. M., Kopin I. J. A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. Proc. Natl. Acad. Sci. USA 1983; 80: 4546–4550
  • Davis G. C., Williams A. C., Markey S. P., Ebert M. H., Caine E. D., Reichert C. M., Kopin I. J. Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res. 1979; 1: 249–254
  • Weissman J., Trevor A., Chiba K., Peterson L. A., Caldera P., Castagnoli N., Jr. Metabolism of the nigrostriatal toxin 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine by liver homogenate fractions. J. Med. Chem. 1985; 28: 997–1001
  • DiMonte D., Shinka T., Sandy M. S., Castagnoli N., Jr., Smith M. T. Quantitative analysis of l-methyl-4-phenyl-l,2,3,6-tetrahy-dropyridine metabolism in isolated rat hepatocytes. Drug. Metab. Dispos. 1988; 16: 250–255
  • Riachi N. J., La Manna J. C., Harik S. I. Entry of 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine into the rat brain. J. Pharmacol. Exp. Then 1989; 249: 744–748
  • Markey S. P., Johannessen J. N., Chiueh C. C., Burns R. S., Herkenham M. A. Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 1984; 311: 464–467
  • Heikkila R. E., Manzino L., Cabbat F. S., Duvoisin R. C. Protection against the dopaminergic neurotoxicity of l-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984; 311: 467–469
  • Shinka E. WuT., Caldera-Munoz P., Yoshizumi H., Trevor A., Castagnoli N., Jr. Metabolic studies on the nigrostriatal toxin MPTP and its MAO B generated dihydropyridinium metabolite MPDP+. Chem. Res. Toxicol. 1988; 1: 186–194
  • Heikkila R. E., Kindt M. V., Sonsalla P. K., Giovanni A., Youngster S. K., McKeown K. A., Singer T. P. Importance of monoamine oxidase A in the bioactivation of neurotoxic analogs of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. Proc. Natl. Acad. Sci. USA 1988; 85: 6172–6176
  • Chiba K., Trevor A., Castagnoli N., Jr. Metabolism of the neurotoxic amine, MPTP, by brain monoamine oxidase. Biochem. Bio-phys. Res. Commun. 1984; 120: 574–578
  • Heikkila R., Duvoisin R. C., Finberg J. P. M., You-dim M. B. H. Prevention of MPTP-induced neurotoxicity by AGN-1I33 and AGN-1135, selective inhibitors of monoamine oxidase-B. Eur. J. Pharmacol. 1985; 116: 313–317
  • Youngster S. K., Sonsalla P. K., Sieber B. -A., Heikkila R. E. Structure-activity study of the mechanism of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. I. Evaluation of the biological activity of MPTP analogs. J. Pharmacol. Exp. Then 1989; 249: 820–828
  • Niwa T., Yoshizumi H., Tatematsu A., Matsuura S., Nagatsu T. Presence of tetrahydroisoquinoline, a parkinsonism-related compound, in food. J. Chromatogn 1989; 493: 347–352
  • Niwa T., Takeda N., Sasaoka T., Kaneda N., Hashizume Y., Yoshizumi H., Tatematsu A., Nagatsu T. Detection of tetrahydroisoquinoline in parkinsonian brain as an endogenous amine by use of gas chromatography-mass spectrometry. J. Chromatogn 1989; 491: 397–403
  • Niwa T., Takeda N., Kaneda N., Hashizume Y., Nagatsu T. Presence of tetrahydroisoquinoline and 2-methyl-tetrahydroquinoline in parkinsonian and normal human brains. Biochem. Biophys. Res. Commun. 1987; 144: 1084–1089
  • Naoi M., Matsuura S., Takahashi T., Nagatsu T. AN-methyltransferase in human brain catalyzes W-methylation of 1,2,3,4,-tetrahydroisoquinoline into N-methyl-1,2,3,4-tetrahydroiso-quinoline, a precursor of a dopaminergic neurotoxin, /V-methyliso-quinolinium ion. Biochem. Biophys. Res. Commun. 1989; 161: 1213–1219
  • Naoi M., Matsuura S., Parvez H., Takahashi T., Hirata Y., Mi-nami M., Nagatsu T. Oxidation of N-methyl-1,2,3,4,-tetrahydro-isoquinoline into the, /V-methyl-isoquinolinium ion by monoamine oxidase. J. Neurochem. 1989; 52: 653–655
  • Nagatsu T., Yoshida M. An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigros-triatal regions. Neurosci. Lett. 1988; 87: 178–182
  • Buege J. A., Aust S. D. Microsomal lipid peroxidation. Meth. Enzymol. 1978; 52: 302–310
  • Sugimoto E., Takahashi N., Kitagawa Y., Chiba H. Intracellular localization and characterization of beef liver aldehyde dehydrogenase isozymes. Agric. Biol., Chem. 1976; 40: 2063–2070
  • Bhuyan K. C., Bhuyan D. K., Podos S. M. Evidence of increased lipid peroxidation in cataracts. 1RCS Medical Sci.: Biochem.; Clin. Biochem. 1981; 9: 126–127
  • Benedetti A., Comporti M., Esterbauer H. Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. Biochim. Biophys. Acta 1980; 620: 281–296
  • Susilo R., Damm H., Rommelspacher H. Formation of a new biogenic aldehyde adduct by incubation of tryptamine with rat brain tissue. J. Neurochem. 1988; 50: 1817–1824
  • Nilsson G. E., Tottmar O. Biogenic aldehydes in brain: On their preparation and reactions with rat brain tissue. J. Neurochem. 1987; 48: 1566–1572
  • Case G. L., Benevenga N. J. Significance of formate as an intermediate in the oxidation of the methionine, 5-methyl-L-cysteine and sarcosine methyl carbons to C02 in the rat. J. Nutr. 1977; 107: 1665–1676
  • Cochin J., Axelrod J. Biochemical and pharmacological changes in the rat following chronic administration of morphine, nalorphine and normorphine. J. Biol. Chem. 1959; 125: 105–110
  • Uotila L., Koivusalo M. Formaldehyde dehydrogenase. Meth. Enzymol. 1981; 77: 314–320
  • Cohen G., Collins M. Alkaloids from catecholamines in adrenal tissue: Possible role in alcoholism. Science 1970; 167: 1749–1751
  • Tuma D. J., Newman M. R., Donohue T. M., Jr., Sorrel M. F. Covalent binding of acetaldehyde to proteins: Participation of lysine residues. Alcoholism 1987; 11: 579–584
  • Israel Y. Covalent binding of acetaldehyde to liver tubulin: A step in the right direction. Hepatology 1989; 9: 161–162
  • Jennet R. B., Sorrell M. F., Saffari-Fard A, Ockner J. L., Tuma D. J. Preferential covalent binding of acetaldehyde to the a-chain of purified rat liver tubulin. Hepatology 1989; 9: 57–62
  • Stevens V. J., Fantl W. J., Newman C. B. Acetaldehyde adducts with hemoglobin. J. Clin. Invest. 1981; 67: 361–369
  • Donohue T. M., Jr., Tuma D. J., Sorrell M. F. Acetaldehyde adducts with proteins: Binding of [14C]acetaldehyde to serum albumin. Arch. Biochem. Biophys. 1983; 220: 239–246
  • Jennett R. B., Saffari-Fard A., Sorrell M. F., Smith S. L., Tuma D. J. Increased covalent binding of acetaldehyde to calmodulin in the presence of calcium. Life Sci. 1989; 45: 1451–1466
  • Smith S. L., Jennett R. B., Sorrell M. F., Tuma D. J. Acetaldehyde substoichiometrically inhibits bovine neurotubulin polymerization. J. Clin. Invest. 1989; 84: 337–341
  • Blaner W. S., Churchich J. Succinic semialdehyde dehydrogenase. Reactivity of lysyl residues. J. Biol. Chem. 1979; 254: 1794–1798
  • Frankel-Conrat H., Singer B. Nucleoside adducts are formed by cooperative reaction of acetaldehyde and alcohols: Possible mechanism for the role of ethanol in carcinogenesis. Proc. Natl. Acad. Sci. USA 1988; 85: 3758–3761
  • Schatzkin A., Jones D. Y., Hoover R. N., Taylor P. R., Brinton L. A., Ziegler R. G., Harvey E. B., Carter C. L., Licitra L. M., Dufour M. C., Larson D. B. Alcohol consumption and breast cancer in the epidemiologic follow-up study of the first national health and nutrition examination survey. N. Engl. J. Med. 1987; 316: 1169–1173
  • Willett W. C., Stampfer M. J., Colditz G. A., Rosner B. A., Hennekens C. H., Speizer F. E. Moderate alcohol consumption and the risk of breast cancer. N. Engl. J. Med. 1987; 316: 1174–1180
  • Murphy S. D. Casarett and Doull's Toxicology third ed., C. D. Klaassen, M. O. Amdur, J. Doull. Macmillan, New York 1986; 519–581
  • Abou-Donia M. B. Organophosphorus ester-induced delayed neurotoxicity. Ann. Rev. Pharmacol. Toxicol. 1981; 21: 511–548
  • Mackness M. I. A-esterases: Enzymes looking for a role?. Biochem. Pharmacol. 1989; 38: 385–390
  • Johnson M. K. Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential. Arch. Toxicol. 1977; 37: 113–115
  • Padilla S., Veronesi B. The relationship between neurological damage and neurotoxic esterase inhibition in rats acutely exposed to tri-ortho-cresyl phosphate. Toxicol. Appl. Pharmacol. 1985; 78: 78–87
  • Dudek B. R., Richardson R. J. Evidence for the existence of neurotoxic esterase in neural and lymphatic tissue of the adult hen. Biochem. Pharmacol. 1982; 31: 1117–1121
  • Mackness M. L., Thompson H. M., Hardy A. R., Walker C. H. Distinction between “A” esterases and arylesterases. Biochem. J. 1987; 245: 293–296
  • Johnson M. K. Organophosphates and delayed neuropathy–is NTE alive and well?. Toxicol. Appl. Pharmacol. 1990; 102: 385–399
  • Moretto A., Lotti M. Organ distribution and delayed neuropathy target esterase in man. Biochem. Pharmacol. 1988; 37: 3041–3043
  • Johnson M. K. Initiation of organophosphate neurotoxicity. Toxicol. Appl. Pharmacol. 1981; 61: 480–481
  • Lotti M., Johnson M. K. Neurotoxic esterase in human nervous tissue. J Neurochem. 1980; 34: 747–749
  • Pope C. N., Padilla S. S. Chromatographic characterization of neurotoxic esterase. Biochem. Pharmacol. 1989; 38: 181–188
  • Yu P. H., Boulton A. A. Regional oxidation of tyramine isomers in rat brain. J. Neurochem. 1980; 35: 255–257
  • Goldberg R., Tipton K. F. The distribution of catechol-O-methyltransferase in pig liver and brain. Biochem. Pharmacol. 1978; 27: 2623–2629
  • Hiemke C., Ghraf R. Distribution and properties of thiol S-methyltransferase in rat brain. J. Neurochem. 1983; 40: 592–594
  • Loscher W., Frey H. -H. Transport of GABA at the blood-CSF interface. J. Neurochem. 1982; 38: 1072–1079
  • Snodgrass S. R., Lorenzo A. V. Transport of GABA from the perfused ventricular system of the cat. J. Neurochem. 1973; 20: 761–769
  • Coceani F. Prostaglandins and the central nervous system. Arch. Intern. Med. 1974; 133: 119–129
  • Nakano J., Prancan A. V., Moore S. E. Metabolism of prostaglandin E, in the cerebral cortex and cerebellum of the dog and rat. Brain Res. 1972; 39: 545–548
  • Wolfe L. S., Rostworowski K., Pappus H. M. The endogenous biosynthesis of prostaglandins by brain tissue in vitro. Can. J. Bio-chem. 1976; 54: 629–640
  • Pace-Asciak C. R., Rangaraj G. Prostaglandin biosynthesis and catabolism in the developing fetal sheep brain. J. Biol. Chem. 1976; 251: 3381–3385
  • Abdel-Halim M. S., Anggard E. Regional and species differences in endogenous prostaglandin biosynthesis by brain homoge-nates. Prostaglandins 1979; 17: 411–418
  • Dixon R. L., Owens E. S., Rail D. P. Evidence of active transport of benzyl-l4C-penicillin from cerebrospinal fluid to blood. JPharm. Sci. 1969; 58: 1106–1109
  • Dacey R. G., Sande M. A. Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrob. Ag. Chemother. 1974; 6: 437–441
  • Cutler R. W. P., Lorenzo A. V. Transport of 1-aminocyclo-pentane-carboxylic acid from feline cerebrospinal fluid. Science 1968; 161: 1363–1364
  • Asghar K., Way E. L. Active removal of morphine from the cerebral ventricles. J. Pharmacol. Exp. Then 1970; 175: 75–83
  • Spector R., Lorenzo A. V. The transport and metabolism of salicylate in the central nervous system: In vivo studies. J. Pharmacol. Exp. Ther. 1973; 185: 276–286
  • Oldendorf W. H. Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids. Am. J. Physiol. 1973; 224: 1450–1453
  • Conn A. R., Fell D. I., Steele R. D. Characterization of ot-keto acid transport across blood-brain barrier in rats. Am. J. Physiol. 1983; 245: E253–E260
  • Steele R. D. Blood-brain barrier transport of the a-keto acid analogs of amino acids. Fed. Proc 1986; 45: 2060–2064
  • Huang J. T. Accumulation of peptide tyr-D-ala-gly by choroid plexus during ventriculocisternal perfusion of rat brain. Neurochem. Res. 1982; 7: 1541–1548
  • Lanman R. C., Schanker L. S. Transport out of the cranial cerebrospinal fluid spaces of the rabbit. JPharmacol. Exp. Ther. 1980; 215: 563–568
  • Lorenzo A. V. Factors governing the composition of the cerebrospinal fluid. Exp. Eye Res. 1977; 205–228, Suppl.
  • Bradbury M. W. B. The structure and function of the blood-brain barrier. Fed. Proc 1984; 43: 186–190
  • Spector R., Sivesind C., Kinzenbaw D. Pantothenic acid transport through the blood-brain barrier. J. Neurochem. 1986; 47: 966–971
  • Pardridge W. M., Mietus L. J. Transport of steroid hormones through the rat blood-brain barrier. J. Clin. Invest. 1979; 64: 145–154
  • Pardridge W. M. Carrier-mediated transport of thyroid hormones through the rat blood-brain barrier: Primary role of albumin-bound hormone. Endocrinology 1979; 105: 605–612
  • Terasaki T., Pardridge W. M. Stereospecificity of triiodothyronine transport into brain, liver, and salivary gland: Role of carrier-and plasma protein-mediated transport. Endocrinology 1987; 121: 1185–1191
  • Bowman P. D., Betz A. L., Goldstein G. W. Primary culture of microvascular endothelial cells from bovine retina: Selective growth using fibronectin coated substrate and plasma derived serum. In Vitro 1982; 18: 626–632
  • Dorovini-Zis K., Bowman P. D., Betz A. L., Goldstein G. W. Formation of a barrier by brain microvessel endothelial cells in culture. Fed. Proc. 1987; 46: 2521–2522
  • Kalaria R. N., Harik S. I. Blood-brain barrier monoamine oxidase: Enzyme characterization in cerebral microvessels and other tissues from six mammalian species, including human. J. Neurochem. 1987; 49: 856–864
  • Savion N., Farzame N. Characterization of the Na,K-ATPase pump in cultured bovine corneal endothelial cells. Exp. Eye Res. 1986; 43: 355–363
  • Jaffe G. J., Burke J. M., Geroski D. H. Ouabain-sensitive Na+-K+ ATPase pumps in cultured human retinal pigment epithelium. Exp. Eye Res. 1989; 48: 61–68
  • Bresnick E. Drug metabolism: Speculations on the future. Drug Me tab. Rev. 1979; 10: 311–313
  • Hardebo J. E., Emson P. C., Falck B., Owman C., Rosen-gren E. Enzymes related to monoamine transmitter metabolism in brain microvessels. J. Neurochem. 1980; 35: 1388–1393
  • Haenick D. H., Ladman R. K., Weiss J., Boehme D. H., Vogel W. H. Monoamine oxidase activities in human brain microvessels. Experientia 1981; 37: 764–765
  • Lasbennes F., Sercombe R., Seylaz J. Monoamine oxidase activity in brain microvessels determined using natural and artificial substrates: Relevance to the blood-brain barrier. J. Cerebral Blood Flow and Metabolism 1983; 3: 521–528
  • Scriba G. K. E., Borchardt R. T. Metabolism of catecholamine esters by cultured bovine brain microvessel endothelial cells. J. Neu-rochem. 1989; 53: 610–615
  • Lorenzo A. V., Hammerstad J. P., Cutler R. W. P. The effect of anaesthetic agents on the cerebrospinal fluid clearance of 35S-sulphate and l25I-iodide. Biochem. Pharmacol. 1968; 17: 1279–1283
  • Wolfson L. I., Katzman R., Escriva A. Clearance of amine metabolites from the cerebrospinal fluid: The brain as a “sink,”. Neurology 1974; 24: 772–779
  • Davson H. Physiology of the Cerebrospinal Fluid. Little, Brown, Boston 1967
  • Neff N. H., Tozer T. N., Brodie B. B. Application of steady-state kinetics to studies of the transfer of 5-hydroxyindoleacetic acid from brain to plasma. J. Pharmacol. Exp. Then 1967; 158: 214–218
  • Anderson J. A., Davis W. L., Wei C. -P. Site of ocular hydrolysis of a prodrug, dipivefrin, and a comparison of its ocular metabolism with that of the parent compound, epinephrine. Invest. Ophthalmol. Vis. Sci. 1980; 19: 817–823
  • Redell M. A., Yang D. C., Lee V. H. L. The role of esterase activity in the ocular disposition of dipivalyl epinephrine in rabbits. Int. J. Pharmaceut. 1983; 17: 299–312
  • Schoenwald R. D., Chien D. S. Ocular absorption and disposition of phenylephrine and phenylephrine oxazolidine. Biopharm. Drug Dispos. 1988; 9: 527–538
  • Schoenwald R. D., Huang H. -S. Corneal penetration behavior of B-blocking agents. I. Physicochemical factors. J. Pharm. Sci. 1983; 72: 1266–1271
  • Chang S. -C., Chien D. -S., Bundgaard H., Lee V. H. L. Relative effectiveness of prodrug and viscous solution approaches in maximizing the ratio of ocular to systemic absorption of topically applied timolol. Exp. Eye Res. 1988; 46: 59–69
  • Chang S. -C., Bundgaard H., Buur A., Lee V. H. L. Low dose O-butyryl timolol improves the therapeutic index of timolol in the pigmented rabbit. Invest. Ophthalmol. Vis. Sci. 1988; 29: 626–629
  • Potter D. E., Shumate D. J., Bundgaard H., Lee V. H. L. Ocular and cardiac B-antagonism by timolol prodrugs, timolol and levobunolol. Curr. Eye Res. 1988; 7: 755–759
  • Buur A., Bundgaard H., Lee V. H. L. Prodrugs of propranolol: Hydrolysis and intramolecular aminolysis of various propranolol esters and an oxazolidin-2-one derivative. Int. J. Pharmaceut. 1988; 42: 51–60
  • Suzuki F., Hayashi H., Ito S., Hayaishi O. Methyl ester of prostaglandin D2 as a delivery system into brain. Biochim. Biophys. Acta 1987; 917: 224–230
  • Bito L. Z., Baroody R. A. The ocular pharmacokinetics of ei-cosanoids and their derivatives. 1. Comparisons of ocular eicosanoid penetration and distribution following the topical application of PGF2oi, PGF2a-l-methyl ester, and PGF2u-l-isopropyl ester. Exp. Eye Res. 1987; 44: 217–226
  • Bundgaard H., Falch E., Larsen C., Mosher G. L., Mikkel-son T. J. Pilocarpic acid esters as novel sequentially labile pilocarpine prodrugs for improved ocular delivery. J. Med. Chem. 1985; 28: 979–981
  • Mitra A. K., Mikkelson Y. J. Mechanism of transcorneal permeation of pilocarpine. J. Pharm. Sci. 1988; 77: 771–775
  • Chiou G. C. Y., Chuang C. Y., Chang M. S. Systemic delivery of enkephalin peptide through eyes. Life Sci. 1988; 43: 509–514
  • Narurkar M. M., Mitra A. K. Prodrugs of 5-iodo-2′ deoxyuri-dine for enhanced ocular transport. Pharmaceut. Res. 1989; 6: 887–891
  • Tsuji A., Tamai I., Sasaki K. Hydrolysis of prednisolone succinate by esterase in rabbit ocular tissues. Ophthalmic Res. 1987; 19: 322–329
  • Pardridge W. M. Strategies for drug delivery through the blood-brain barrier. Directed Drug Delivery, R. T. Borchardt, A. J. Repta, V. J. Stella. Humana Press, Clifton, NJ 1985; 83–96
  • Bodor N. Redox drug delivery systems for targeting drugs to the brain. Ann. NY Acad. Sci. 1987; 507: 289–306
  • Bodor Koussi N., El A. Novel “soft” B-blockers as potential safe antiglaucoma agents. Curr. Eye Res. 1988; 7: 369–374
  • Audus K. L., Bartel R. L., Hidalgo I. J., Borchardt R. T. The use of cultured epithelial and endothelial cells for drug transport and metabolism studies. Pharmaceut. Res. 1990; 7: 435–451
  • Rapoport S. I., Fredericks W. R., Ohno K., Pettigrew K. D. Quantitative aspects of reversible osmotic opening of the blood-brain barrier. Am. J. Physiol. 1980; 238: R421–R431
  • Li V., Turski P. A., Levin A. B., Weinstein J., Rozentai J., Strother C. M. Osmotic disruption of the blood-ocular barriers. Am. J. Neuroradiol. 1987; 8: 347–348
  • Pickard J. D., Durity F., Welch F. A., Langfitt T. -W., Harper A. M., MacKenzie E. T. Osmotic opening of the blood-brain barrier: Value in pharmacological studies on the cerebral circulation. Brain Res. 1977; 122: 170–176
  • Brightman M. W. Morphology of blood-brain interfaces. Exp. Eye Res. 1977; 1–25, Suppl.
  • Heistad D. D. Protection of the blood-brain barrier during acute and chronic hypertension. Fed. Proc 1984; 43: 205–209
  • Hirano A., Ghatak N. R., Becker N. H., Zimmerman H. M. A comparison of the fine structure of small blood vessels in intracranial and retroperitoneal malignant lymphomas. Acta Neuropathol. 1971; 27: 93–104, as cited by Bradbury [555]
  • Spector R., Lorenzo A. V. Inhibition of penicillin transport from the cerebrospinal fluid after intracisternal inoculation of bacteria. J. Clin. Invest. 1974; 54: 316–325
  • Cunha-Vaz J., Faria de Abreu J. R., Campos A. J., Figo G. M. Early breakdown of the blood-brain barrier in diabetes. Brit. J. Ophthalmol. 1975; 59: 649–656
  • Deutman A. F. Significance of alteration of the outer blood-retinal barrier. The Blood-Retinal Barriers, J. G. Cunha-Vaz. Plenum Press, New York 1979; 365–374
  • Goldberg M. F. Diseases affecting the inner blood-retinal barrier. The Blood-Retinal Barriers, J. G. Cunha-Vaz. Plenum Press, New York 1979; 309–310
  • Mallick K. S., Zeimer R. C., Fishman G. A., Blair N. P., Anderson R. J. Transport of fluorescein in the ocular posterior segment in retinitis pigmentosa. Arch. Opthalmol. 1984; 102: 691–696
  • Neuwelt E. A., Rapoport S. I. Modification of the blood-brain barrier in the chemotherapy of malignant brain tumors. Fed. Proc 1984; 43: 214–219
  • McGahan M. C. Ascorbic acid levels in aqueous and vitreous humors of the rabbit: Effects of inflammation and ceruloplasmin. Exp. Eye Res. 1985; 41: 291–298
  • Ficker L., Meredith T. A., Gardner S., Wilson A. L. Cefazolin levels of after intravitreal injection. Effects of inflammation and surgery. Invest. Ophthalmol. Vis. Sci. 1990; 31: 502–505
  • Sanders D. R., Kraff M. C., Lieberman H. L., Peyman G. A., Tarabishy S. Breakdown and reestablishment of blood-aqueous barrier with implant surgery. Arch. Ophthalmol. 1982; 100: 588–590
  • Sloane J. P., Lwin K. Y., Gore M. E., Powles R. L., Smith J. F. Disturbance of blood-brain after bone-marrow transplantation. Lancet 1985; 2: 280–281
  • Eakins K. E. Prostaglandin-and non-prostaglandin-mediated breakdown of the blood-aqueous barrier. Exp. Eye Res. 1977; 25: 483–498, Suppl.
  • Tsuboi S., Tsuboi J. E. Pederson, Acetazolamide effect on the inward permeability of the blood-retinal barrier to carboxyfluorescein. Invest. Ophthalmol. Vis. Sci. 1987; 28: 92–95
  • Saija A., Princi P., De Pasquale R., Costa G. Arecoline, but not haloperidol, induces changes in the permeability of the blood-brain barrier in the rat. J. Pharm. Pharmacol 1989; 42: 135–138
  • Novack G. D., Leopold I. H. The blood-aqueous and blood-brain barriers to permeability. Am. J. Ophthalmol. 1988; 105: 412–416
  • Pardridge W. M., Connor J. D., Crawford I. L. Permeability changes in blood-brain barrier: Causes and consequences. CRC Crit. Rev. Toxicol. 1975; 3: 159–199
  • Plazonnet B., Grove J., Durr M., Mazuel C., Quint M., Ro-zier A. Pharmacokinetics and biopharmaceutical aspects of some anti-glaucoma drugs. Ophthalmic Drug Delivery: Biopharmaceutical, Technological and Clinical Aspects. Liviana Press/Springer-Verlag, Berlin 1987; vol. 11: 118–139
  • Nabeshima T., Fontenot J., Ho I. K. Effects of chronic administration of pentobarbital or morphine on the brain microsomal cytochrome P-450 system. Biochem. Pharmacol. 1981; 30: 1142–1145
  • Rang Y. S., Terasaki T., Ohnishi T., Tsuji A. In vivo and in vitro evidence for a common carrier mediated transport of choline and basic drugs through the blood–brain barrier. J. Pharmacohio-Dyn. 1990; 13: 353–360

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