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Development of Antidepressant Drugs

Fluoxetine (Prozac) and Other Selective Serotonin Uptake Inhibitors
  • David T. Wong
  • Frank P. Bymaster
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 363)

Abstract

Active uptake processes have been described for the monoaminergic neurotransmitters including serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA) in nervous tissues (Whitby, Axelrod, and Weil-Malherbe, 1961; Burgen and Iverson, 1965; Iverson, 1971). The uptake of 5-HT and NE in brain tissues has been the target sites in our search of selective inhibitors, which may have therapeutic potential for treatment of depressive disorders (Wong et al., 1974; 1975a; 1993a). Fluoxetine [Prozac], a member of the substituted phenoxyphenylpropylamines, was the first selective 5-HT uptake inhibitor to appear in the scientific literature (Wong et al, 1974) and has served as a useful tool to establish the physiological role of 5-HT neurons and a reference of pharmacological responses indicative of an enhanced transmission of 5-HT neurons (Fuller and Wong, 1977; Wong and Fuller, 1987; Wong and Murphy, 1989; Fuller and Wong, 1990). After its introduction in 1988, fluoxetine (Prozac) has become a major antidepressant drug in the United States and in many countries (Beasley et al., 1990; Boyer and Feighner, 1991a). In the U.S., two other selective 5-HT uptake inhibitors, sertraline and paroxetine, have been introduced as antidepressant drugs. In this article, we present some of the background which attracted our attention, and some studies on the chemical series of phenoxyphenylpropylamines and the enantiomers of fluoxetine and its major metabolite norfluoxetine as inhibitors of 5-HT and NE uptake in vitro. We also present the consequences of 5-HT reuptake inhibition in vivo, and the contrast between the classical tricyclic antidepressant drugs and the newly developed selective 5-HT reuptake inhibitors in terms of their interaction with receptors of neurotransmitters.

Keywords

Reuptake Inhibitor Tertiary Amine Antidepressant Drug Uptake Inhibitor Serotonin Uptake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adell, A. and Artigas, F. (1991).Differential effects of clomipramine given locally or systemically on extracellular 5-hydroxytryptamine in raphe nuclei and frontal cortex: an in vivo brain microdialysis study. Naunyn-Schmiedeberg’s Arch. Pharmacol. 343: 237–244.Google Scholar
  2. Asberg, M., Bertilsson, L., Tuck, D. et al. (1973).Indolamine metabolites in the cerebrospinal fluid of depressed patients before and during treatment with nortriptyline. Clin. Pharmacol. Ther. 14: 277–286.PubMedGoogle Scholar
  3. Asberg, M, Bertilsson, L., Martensson, B. et al. (1986).Therapeutic effects of serotonin uptake inhibitors in depression. J. Clin. Psychiatry 47 (suppl): 23–35.PubMedGoogle Scholar
  4. Asberg, M. and Wagner, A. (1986). Biochemical effects of antidepressant treatment-studies of monoamine metabolites in cerebrospinal fluid and platelet [H]imipramine, in “Antidepressants and Receptor function,” Wiley, Chichester, Ciba Foundation Symposium 123: 57–83.Google Scholar
  5. Aschroft, G. W., Crawford, T. B. B. and Eccleston, D. (1966).5-Hydroxyindole compounds in the cerebrospinal fluid of patients with psychiatric or neurological diseases. Lancet11: 1049–1050.Google Scholar
  6. Auerbach, S. B., Minzenberg, M. J. and Wilkinson, L. O. (1989).Extracellular serotonin and 5-hydroxyindoleacetic acid in hypothalamus of the unanesthetized rat measured by in vivo dialysis coupled to high-performance liquid chromatography with electrochemical detection: dialysate serotonin reflects neuronal release. Brain Res. 499: 281–290.PubMedCrossRefGoogle Scholar
  7. Barrett, R. J., Blackshear, M. A. and Sanders-Bush, E. (1982).Discriminative stimulus properties of L-5-hydroxytryptophan: Behavioral evidence for multiple serotonin receptors. Psychopharmacology 76: 29–35.PubMedCrossRefGoogle Scholar
  8. Beasley, C. M., Bosomworth, J. C. and Wernicke, J. F. (1990).Fluoxetine: relationship among dose, response, adverse events, and plasma concentrations in the treatment of depression. Psychopharmacol. Bull. 26: 18–24.PubMedGoogle Scholar
  9. Bjerkenstedt, L., Edman, G., Flyckt, L. et al. (1985).Clinical and biochemical effects of citalopram, a selective 5-HT reuptake inhibitor-a dose-response study in depressed patients. PsychopharmacoL 87: 253–259.CrossRefGoogle Scholar
  10. Bolden-Watson, C. and Richelson, E. (1993).Blockade by newly developed anti-depressants of biogenic amine uptake into rat brain synaptosomes. Life Sci. 52: 1023–1029.PubMedCrossRefGoogle Scholar
  11. Bourin, M. (1990).Is it possible to predict the activity of a new antidepressant in animals with simple psychopharmacological tests? Fundam. Clin. Pharmacol. 4: 49–64.Google Scholar
  12. Boyer, W. E. and Feighner, J. D. (1991a). The efficacy of selective serotonin re-uptake inhibitors in depression, in “Selective Serotonin Re-Uptake Inhibitors, The Clinical Use of Citalopram, Fluoxetine, Fluvoxamine, Paroxetine and Sertraline,” J. D. Feighner and W. E. Boyer, eds., John Wiley & Son, Chichester, England, pp. 89–108.Google Scholar
  13. Boyer, W. E. and Feighner, J. D. (1991b). Side-effects of the selective serotonin re-uptake inhibitors, ibid, pp. 133-152.Google Scholar
  14. Bremner, J. D. (1984).Fluoxetine in depressed patients: a comparison with imipramine. J. Clin. Psychiatry 45: 414–419.PubMedGoogle Scholar
  15. Broune, H. R., Bunney, W. E., Jr., Colbum, R. W. et al. (1968).Noradrenaline, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in hindbrains of suicidal patients. Lancet 11: 805–808.CrossRefGoogle Scholar
  16. Burgen, A.S.V. and Iversen, L.L. (1965).The inhibition of noradrenaline uptake by sympathomimetic amines in the rat isolated heart. Brit. J. Pharmacol. 25: 34–49.PubMedGoogle Scholar
  17. Bymaster, F. P. and Wong, D. T. (1977).Effect of Lilly 110140, 3-(p-trifluoro-methylphenoxy)-N-methyl-3-phenylpropylamine on synthesis of 3H-serotonin from 3H-tryptophan in rat brain. The Pharmacologist 16: 244.Google Scholar
  18. Carboni, E. and Di Chiara, G. (1989).Serotonin release estimated by transcortical dialysis in freely-moving rats. Neuroscience 32: 637–645.PubMedCrossRefGoogle Scholar
  19. Carlsson, A. (1970).Structural specificity for inhibition of [14C]-5-hydroxytryptamine uptake by cerebral slices. J. Pharm. Pharmacol. 22: 729–732.PubMedCrossRefGoogle Scholar
  20. Carlsson, A., Fuxe, K., Hamberger, B. and Lindqvist, M. (1966).Biochemical and histochemical studies on the effects of imipramine-like drugs and (+)-amphetamine on central and peripheral catecholamine neurons. Acta Physiol. Scand. 67: 481–497.PubMedCrossRefGoogle Scholar
  21. Carlsson, A., Corrodi, H., Fuxe, K. and Hokfelt, T. (1969a). Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-a-ethyl-meta-tyramine. Eur. J. Pharmacol. 5: 357–366.PubMedCrossRefGoogle Scholar
  22. Carlsson, A., Corrodi, H., Fuxe, K. and Hokfelt, T. (1969b).Effects of some antidepressant drugs on the depletion of intraneuronal brain catecholamine stores caused by 4, a-dimethyl-meta-tyramine. Eur. J. Pharmacol. 5: 367–373.PubMedCrossRefGoogle Scholar
  23. Carlsson, A., Fuxe, K. and Ungerstedt, U. (1968).The effects of imipramine of central 5-hydroxytryptamine neurons. J. Pharm. Pharmacol. 20: 150–151.PubMedCrossRefGoogle Scholar
  24. Chaput, H., de Montigny, C. and Blier, P. (1986).Effects of a selective 5-HT reuptake blocker, citalopram, on the sensitivity of 5-HT autoreceptors: electrophysiological studies in the rat brain. Naunyn-Schmiedeberg’s Arch. Pharmacol. 333: 342–348.CrossRefGoogle Scholar
  25. Claassen, V., Davis, J. E., Hertting, G. et al. (1977).Fluvoxamine, a specific 5-hydroxytryptamine uptake inhibitor. Brit. J. Pharmacol. 60: 505–516.CrossRefGoogle Scholar
  26. Clemens, J. A., Sawyer, B. D. and Cerimele, B. (1977).Further evidence that serotonin is a neurotransmitter involved in the control of prolactin secretion. Endocrinology 100: 692–698.PubMedCrossRefGoogle Scholar
  27. Cohn, J. B. and Wilcox, C. S. (1992).Paroxetine in major depression: a double-blind trial with imipramine and placebo. J. Clin. Psychiatry 53: 2 (suppl) 52–56.PubMedGoogle Scholar
  28. Coppen, A. J., Prange, A. K. and Whybrow, P. C. (1972).Abnormalities of indoleamines in affective disorders. Arch. Gen. Psychiatry 26: 474–478.PubMedCrossRefGoogle Scholar
  29. Coppen, A., Shaw, D. M., and Farrell, J. P. (1963).Potentiation of the antidepressive effect of a monoamine oxidase inhibitor by tryptophan. Lancet 1: 79–81.PubMedCrossRefGoogle Scholar
  30. Coppen, A., Shaw, D. M., Herzberg, B. and Maggs, R. (1967).Tryptophan in the treatment of depression. Lancet 11: 1178.CrossRefGoogle Scholar
  31. Corrodi, H. and Fuxe, K. (1968).The effects of imipramine on central monoamine neurones. J. Pharm. Pharmacol. 20: 230–231.PubMedCrossRefGoogle Scholar
  32. Dahlstrom, A. and Fuxe, K. (1964).Evidence for the existence of monoamine-containing neurons in the central nervous system. 1. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand. 62: suppl. 232: 6–55.Google Scholar
  33. Dailey, J.W., Yan, Q.S., Mishra, P.K. et al. (1992).Effects of fluoxetine on convulsions and in brain serotonin as detected by microdialysis in genetically epilepsy-prone rats. J. Pharmacol. Exp. Ther. 260: 533–540.PubMedGoogle Scholar
  34. Delgado, P. L., Charney, D. S., Price, L. H. et al. (1990).Serotonin function and the mechanism of antidepressant action. Arch. Gen. Psychiatry 47: 411–418.PubMedCrossRefGoogle Scholar
  35. Dencker, S. J., Malm, U., Roo, B. E. et al. (1966).Acid monoamine metabolites of cerebrospinal fluid in mental depression and mania. J. Neurochem. 13: 1545–1548.PubMedCrossRefGoogle Scholar
  36. Dengler, H.J. and Titus, E.O. (1961).The effect of drugs on the uptake of isotopic norepinephrine in various tissues. Biochem. Pharmacol. 8: 64.CrossRefGoogle Scholar
  37. Dominguez, R. A., Goldstein, B. J., Jacobson, A. F. and Steinbook, R. M. (1985).A double-blind placebo-controlled study of fluvoxamine and imipramine in depression. J. Clin. Psychiatry 46: 84–87.PubMedGoogle Scholar
  38. Doogan, D. P. and Caillard, V. (1988).Sertraline: A new antidepressant. J. Clin. Psychiatry 49: 8 (suppl) 46–51.PubMedGoogle Scholar
  39. Feighner, J. P. (1985).A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. J. Clin. Psychiatry 46: 69–372.Google Scholar
  40. Flood, J. F. and Cherkin, A. (1987).Fluoxetine enhances memory processing in mice. Psychopharmacology 93: 36–43.PubMedCrossRefGoogle Scholar
  41. Fuller, R. W. (1981).Serotonergic stimulation of pituitary-adrenocortical function in rats. Neuroendocrinology 32: 118–127.PubMedCrossRefGoogle Scholar
  42. Fuller, R. W., Perry, K. W. and Molloy, B. B. (1974).Effect of an uptake inhibitor on serotonin metabolism in rat brain: studies with 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine. Life Sci. 15: 1161–1171.PubMedCrossRefGoogle Scholar
  43. Fuller, R. W., Perry, K. W. and Molloy, B. B. (1975).Effect of 3-(p-trifluoro-methylphenoxy)-N-methyl-3-phenylpropylamine on the depletion of brain serotonin by 4-chloroamphetamine. J. Pharmacol. Exp. Ther. 193: 796–803.Google Scholar
  44. Fuller, R. W. and Wong, D. T. (1977).Inhibition of serotonin reuptake. Fed. Proc.36: 2154–2158.PubMedGoogle Scholar
  45. Fuller, R. W. and Wong, D. T. (1990). Serotonin uptake and serotonin uptake inhibition. Ann. N.Y. Acad. Sci. 600: 68–78.PubMedCrossRefGoogle Scholar
  46. Fuller, R. W., Wong, D.T. and Robertson, D. W. (1991).Fluoxetine, a selective inhibitor of serotonin uptake. Medicinal Res. Rev. 11: 17–34.CrossRefGoogle Scholar
  47. Geyer, M. A., Dawsey, W. J. and Mandell, A. L. (1978).Fading: a new cytofluorimetric measure quantifying serotonin in the presence of catecholamines at the cellular level in brain. J. Pharmacol. Exp. Ther. 207: 650–667.PubMedGoogle Scholar
  48. Gibbs, D. M. and Vale, W. (1983).Effect of the serotonin reuptake inhibitor fluoxetine on corticotropin-releasing factor and vasopressin secretion into hypophysial portal blood. Brain Res. 280: 176–179.PubMedCrossRefGoogle Scholar
  49. Gill, K., Amit, Z. and Koe, B. (1988).Treatment with sertraline, a new serotonin uptake inhibitor, reduces voluntary ethanol consumption in rats. Alcohol 5: 349–354.PubMedCrossRefGoogle Scholar
  50. Glowinski, J. and Axelrod, J. (1964). Inhibition of uptake of tritiated-noradrenaline in the intact rat brain by imipramine and structurally-related compounds. Nature 204: 1318–1319.Google Scholar
  51. Goudie, A. J., Thornton, E. W. and Wheeler, T. J. (1976).Effects of Lilly 110140, a specific inhibitor of 5-hydroxytryptamine uptake, on food intake and 5-hydroxy-tryptophan-induced anorexia. Evidence for serotonergic inhibition of feeding. J. Pharm. Pharmacol. 28: 318–320.Google Scholar
  52. Guan, X. M., and McBride, W. J. (1988).Fluoxetine increases the extracellular levels of serotonin in the nucleus accumbens. Brain Res. Bull. 21: 43–46.PubMedCrossRefGoogle Scholar
  53. Guelfi, J. D., Dreyfus, J. F., Boyer, P. and Pichot, P. (1981). A double-blind controlled multicenter trial comparing indalpine and imipramine. 3rd World Congress of Biological Psychiatry, Stockhohn, June 28-July 3, 1981.Google Scholar
  54. Hall, H. and Ogren, S. O. (1981).Effects of antidepressant drugs on different receptors in rat brain. Eur. J. Pharmacol. 70: 393–407.PubMedCrossRefGoogle Scholar
  55. Heel, R. C., Morley, P. A., Brogden, R. N., et al. (1982).Zimelidine: a review of its pharmacological properties and therapeutic efficacy in depressive illness. Drugs 24: 169–206.PubMedCrossRefGoogle Scholar
  56. Hertting, G., Axelrod, J. and Whitby, L. G. (1961).Effect of drugs on the uptake and mechanism of [3H]-no-repinephrine. J. Pharmacol. Exp. Ther. 134: 146–153.Google Scholar
  57. Hertz, D. and Sulman, F. G. (1968). Preventing depression with tryptophan. Lancet I: 531.Google Scholar
  58. Horng, J. S. and Wong, D. T. (1976).Effects of serotonin uptake inhibitor, Lilly 110140, on transport of serotonin in rat and human blood platelets. Biochem. Pharmacol.25: 865–867.PubMedCrossRefGoogle Scholar
  59. Hyttel, J. (1982).Citalopram-pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Neuro-Psychopharmacol. Biol. Psychiatry 6: 277–295.CrossRefGoogle Scholar
  60. Invernizzi, R., Belli, S. and Samanin, R. (1992).Citalopram’s ability to increase the extracellular concentrations of serotonin in the dorsal raphe prevents the drug’s effect in the frontal cortex. Brain Res. 584: 322–324.PubMedCrossRefGoogle Scholar
  61. Itil, T. M., Shrivastava, R. K., Mukherjee, S. et al. (1983).A double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression. Brit. J. Clin. Pharmacol. 15: 433S–438S.CrossRefGoogle Scholar
  62. Iversen, L. L. (1971).Role of transmitter uptake mechanisms in synaptic neuro-transmission. Brit. J. Pharmacol. 41: 571–591.CrossRefGoogle Scholar
  63. Jenck, F., Moreau, J.-L., Mutel, V. et al. (1993).Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur. J. Pharmacol. 231: 223–229.PubMedCrossRefGoogle Scholar
  64. Jesberger, J. A. and Richardson, J. S. (1985).Animal models of depression: Parallels and correlates to severe depression in human. Biol. Psychiatry 20: 764–784.PubMedCrossRefGoogle Scholar
  65. Joly, D. and Danger, D.J. (1986).The effects of fluoxetine and zimelidine on the behavior of olfactory bulbectomized rats. Pharmacol. Biochem. Behav. 24: 199–204.PubMedCrossRefGoogle Scholar
  66. Kalen, P., Strecker, R. E., Rosengren, E. and Bjorklund, A. (1988).Endogenous release of neuronal serotonin and 5-hydroxyindoleacetic acid in the caudate-putamen of the rat as revealed by intracerebral dialysis coupled to high-performance liquid chromatography with fluorimetric detection. J. Neurochem. 51: 1422–1435.PubMedCrossRefGoogle Scholar
  67. Kline, N. S. and Sacks, W. (1963).Relief of depression within one day using an M.A.O. inhibitor and intravenous 5-HTP. Am. J. Psychiatry, 120: 274.PubMedGoogle Scholar
  68. Koe, K. K., Weissman, A., Welch, W. M. et al. (1983).Sertraline, 1S, 4S-N-methyl-4-(3, 4-dichlorophenyl)-1, 2, 3, 4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin. J. Pharmacol. Exp. Ther. 226: 686–700.PubMedGoogle Scholar
  69. Korpi, E. R., Kleinman, J. E., Goodman, S. I. et al. (1968).Serotonin and 5-hydroxy-indoleacetic acid in brain of suicide victims: Comparison in chronic schizophrenic patients with suicide as cause of death. Arch. Gen. Psychiatry 43: 594–600.CrossRefGoogle Scholar
  70. Krulich, L. (1975).The effect of a serotonin uptake inhibitor (Lilly 110140) on the secretion of prolactin in the rat. Life Sci. 17: 1141–1144.PubMedCrossRefGoogle Scholar
  71. Kuhar, M.J., Shaskan, E.G. and Snyder, S.H. (1971).The subcellular distribution of endogenous and exogenous serotonin in brain tissue: Comparison of synaptosomes storing serotonin, norepinephrine, and gamma-ami-nobutyric acid. J. Neurochem. 18: 333–343.PubMedCrossRefGoogle Scholar
  72. Kuhar, M. J., Roth, R. and Aghajanian, G. K. (1972).Synaptosomes from forebrains of rats with midbrain raphe lesions: selective reduction of serotonin uptake. J. Pharmacol. Exp. Ther. 181: 36–45.PubMedGoogle Scholar
  73. Kuhn, R. (1957).Die behandlung depressiver zustande mit einem iminodebenzylderivat (G22355).Schweiz, und Wschr. 87: 1135–1140.Google Scholar
  74. Lapin, I. P. and Oxenkrug, G. F. (1969).Intensification of the central serotonergic processes as a possible determinant of the thymoleptic effect. Lancet 1: 132–136.PubMedCrossRefGoogle Scholar
  75. Lee, E. H. Y., Lin, W. R., Chen, H. Y. et al. (1992).Fluoxetine and 8-OHDPAT in the lateral septum enhances and impairs retention of an inhibitory avoidance response in rats. Physiol. Behav. 51: 681–688.PubMedCrossRefGoogle Scholar
  76. Lloyd, K. G., Farley, I. J., Deck, J.H.H. et al. (1974).Serotonin and 5-hydroxy-indolacetic acid in discrete areas of the brainstem of suicide victims and control patients. Adv. Biochem. Psychopharmacol. 11: 387–397.PubMedGoogle Scholar
  77. Marsden, C. A., Conti, J., Strope, E. et al. (1979). Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanesthetized rat using in vivo voltammetry. Brain Res. 171: 85–99.Google Scholar
  78. Messing, R. B., Phebus, L., Fisher, L. A. et al. (1975).Analgesic effect of fluoxetine hydrochloride (Lilly 110140), a specific inhibitor of serotonin uptake. Psychopharmacol. Comm. 1: 511–521.Google Scholar
  79. Molina, V.A., Gobaille, S. and Mandel, P. (1986).Effects of serotonin-mimetic drugs on mouse-killing behavior. Aggress. Behav. 12: 201–269.CrossRefGoogle Scholar
  80. Moreau, J.-L., Jenck, F., Martin, J. R. et al. (1993).Effects of repeated mild stress and two antidepressant treatments on the behavioral response to 5-HT1C receptor activation in rats. Psychopharmacology 110: 140–144.PubMedCrossRefGoogle Scholar
  81. Murphy, J. M., Waller, M. B., Gatto, G. J. et al. (1985).Monoamine uptake inhibitors attenuate ethanol intake in alcohol-preferring (P) rats. Alcohol 2: 349–352.PubMedCrossRefGoogle Scholar
  82. Murphy, J. M., Waller, M. B., Gatto, G.J. et al. (1988).Effects of fluoxetine on the intragastric self-administration of ethanol in the alcohol preferring P lines of rats. Alcohol 5: 283–286.PubMedCrossRefGoogle Scholar
  83. Muscettola, G., Goodwin, F. K., Potter, W. Z. et al. (1978).Imipramine and desipramine in plasma and spinal fluid. Arch. Gen. Psychiatry 35: 621–625.PubMedCrossRefGoogle Scholar
  84. Nelson, D. R., Thomas, D. R. and Johnson, A. M. (1989). Pharmacological effects of paroxetine after repeated administration to animals. Acta Psychiatry Scand. 80 (suppl 350), 21–23.CrossRefGoogle Scholar
  85. Nelson, J. C., Mazure, C. M., Bowers, M. B. and Jatlow, P. L. (1991).A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Arch. Gen. Psychiatry 48: 303–307.PubMedCrossRefGoogle Scholar
  86. Ortmann, R., Waldmeier, P. C., Radeke, E. et al. (1980).The effect of 5-HT uptake and MAO-inhibitors on L-5-HTP-induced excitation in rats. Naunyn-Schmiedeberg’s Arch. Pharmacol. 311: 185–192.CrossRefGoogle Scholar
  87. Page, I. H. (1969). Serotonin and the brain, in “The Structure and Function of Nervous Tissue,” G. H. Bourne (ed.), Vol. III, Biochemistry and Disease, Academic Press, NY, pp. 289–307.Google Scholar
  88. Pare, C.M.B. (1963).Potentiation of monoamine oxidase inhibitors by tryptophan. Lancet II: 527–528.CrossRefGoogle Scholar
  89. Parti, C. J. and Hicks, J. (1974).In vivo demethylation of Lilly 110140: 3 (p-trifluoromethylphenoxy)-N-methyl-phenoxy)-N-methyl-3-phenyl propylamine to an active metabolite — Lilly 103947. Fed. Proc. 33: 560.Google Scholar
  90. Pastel, R. H. and Fernstrom, J. D. (1987).Short-term effects of fluoxetine and trifluorophenylpiperazines on electroencephalographic sleep in the rat. Brain Res. 436: 92–102.PubMedCrossRefGoogle Scholar
  91. Perry, K. W. and Fuller R. W. (1992).Effect of fluoxetine on serotonin and dopamine concentration in microdialysis fluid from rat striatum. Life Sci. 50: 1683–1690.PubMedCrossRefGoogle Scholar
  92. Richelson, E. and Nelson, A. (1984).Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J. Pharmacol. Exp. Ther. 230: 94–102.PubMedGoogle Scholar
  93. Robertson, D. W., Jones, N. D., Swartzendruber, J. K. et al. (1987).Molecular structure of fluoxetine hydrochloride, a highly selective serotonin uptake inhibitor. J. Med. Chem. 31: 185–189.CrossRefGoogle Scholar
  94. Rockman, G. E., Amit, Z., Brown, Z. W. et al. (1982).An investigation of the mechanisms of action of 5-hydroxytryptamine in the suppression of ethanol intake. Neuropharmacol. 21: 341–347.CrossRefGoogle Scholar
  95. Ross, S. B. and Renyi, A. L. (1967).Inhibition of the uptake of tritiated catecholamines by antidepressant and related agents. Eur. J. Pharmacol. 2: 181–186.PubMedCrossRefGoogle Scholar
  96. Ross, S. B. and Renyi, A. L. (1969).Inhibition of the uptake of tritiated 5-hydroxy-tryptamine in brain tissue. Eur. J. Pharmacol. 7: 270–277.PubMedCrossRefGoogle Scholar
  97. Roth, B. L., Meltzer, H. Y. and Craigo, S. (1992).Typical tricyclic antidepressants possess potent 5-HT1C receptor activity. Abst. 22nd Ann. Meeting, Society for Neuroscience 18: 522.Google Scholar
  98. Rutter, J. J. and Auerbach, S. B. (1993).Acute uptake inhibition increases extracellular serotonin in the rat forebrain. J. Pharmacol. Exp. Ther. 265: 1319–1324.PubMedGoogle Scholar
  99. Sano, S. (1977).5-Hydroxy-L-tryptophan; a fast-acting drug for endogenous depression. Drugs Exptl. Clin. Res. 1: 239–242.Google Scholar
  100. Scatton, B., Claustre, Y., Graham, D., et al. (1988).SL 81.0385: A novel selective and potent serotonin uptake inhibitor. Drug Dev. Res. 12: 29–40.CrossRefGoogle Scholar
  101. Schmidt, M. J., Fuller, R. W. and Wong, D. T. (1988). Fluoxetine, a highly selective serotonin reuptake inhibitor: a review of preclinical studies. Brit. J. Psychiatr. 153(Suppl 3): 40–46.Google Scholar
  102. Shaskan, E. G. and Snyder, S. H. (1970).Kinetics of serotonin accumulation into slices from rat brain: relationship to catecholamine uptake. J. Pharmacol. Exp. Ther. 175: 404–418.PubMedGoogle Scholar
  103. Shaw, D. M., Camps, F. E. and Eccleston, E. G. (1967).5-Hydroxytrytamine in the hind brain of depressive suicides. Brit. J. Psychiatry 113: 1407–1411.CrossRefGoogle Scholar
  104. Slater, I. H., Jones, G. T. and Moore, R. A. (1978).Inhibition of REM sleep by fluoxetine, a specific inhibitor of serotonin uptake. Neuropharmacol. 17: 383–389.CrossRefGoogle Scholar
  105. Slater, I. H., Rathbun, R. C. and Kattau, R. (1979).Role of 5-hydroxytryptamergic and adrenergic mechanism in antagonism of reserpine-induced hypothermia in mice. J. Pharm. Pharmacol. 31: 108–110.PubMedCrossRefGoogle Scholar
  106. Snyder, S. H. and Coyle, J. T. (1969).Regional differences in 3H-norepinephrine and 3H-dopamine uptake into rat brain homogenates. J. Pharmacol. Exp. Ther., 165: 78–86.PubMedGoogle Scholar
  107. Snyder, S. H. and Yamamura, H. I. (1977).Antidepressants and muscarinic acetylcholine receptor. Arch. Gen. Psychiatry 34: 236–239.PubMedCrossRefGoogle Scholar
  108. Sugrue, M. F. (1979).On the role of 5-hydroxytryptamine in drug-induced antinociception. Brit. J. Pharmacol. 65: 677–681.CrossRefGoogle Scholar
  109. Sulser, F., Watts, J. and Brodie, B. B. (1962).On the mechanism of antidepressant action of imipramine-like drugs. Ann. N. Y. Acad. Sci. 96: 279.PubMedCrossRefGoogle Scholar
  110. Thomas, D. R., Nelson, D. R. and Johnson, A. M. (1987).Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacol. 93: 193–200.Google Scholar
  111. U’Prichard, D. C., Greenberg, D. A., Sheehan, P. B. etal. (1978).Tricyclic anti-depressants; therapeutic properties affinity for a-noradrenergic receptor binding sites in the brain. Sci. 199: 197–198.CrossRefGoogle Scholar
  112. Weil-Malherbe, H. and Szara, S. I. (1971). Brain amines and affective disorders, in “The Biochemistry of Functional and Experimental Psychosis,” Charles C. Thomas Publisher; Springfield, IL, pp. 57–76.Google Scholar
  113. Whitby, L.G., Axelrod, J. and Weil-Malherbe, H. (1961).The fate of H3-norepinephrine in animals. J. Pharmacol. Exp. Ther. 132: 193–201.PubMedGoogle Scholar
  114. Wong, D. T. and Bymaster, F. P. (1976).The comparison of fluoxetine and nisoxetine with tricyclic antidepressants in blocking the neurotoxicity of p-chloroamphetamine and 6-hydroxydopamine in the rat brain. Res. Comm. Chem. Pathol. Pharmacol. 15: 221–231.Google Scholar
  115. Wong, D. T., Bymaster, F. P., Horng, J. S. and Molloy, B. B. (1975a).A new selective inhibitor for uptake of serotonin into synaptosomes of rat brain: 3-(p-trifluoro-methylphenoxy)-N-methyl-3-phenylpropylamine. J. Pharmacol. Exp. Ther. 193: 804–811.PubMedGoogle Scholar
  116. Wong, D. T., Bymaster, F. P., Mayle, D.A. et al. (1993a).LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology 8: 23–33.PubMedGoogle Scholar
  117. Wong, D. T., Bymaster, F. P., Reid, L. R. and Threlkeld, P. G. (1983).Fluoxetine and two other serotonin uptake inhibitors without affinity for neuronal receptors. Biochem. Pharmacol. 32: 1287–1293.PubMedCrossRefGoogle Scholar
  118. Wong, D. T., Bymaster, F. P., Reid et al. (1993b).Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain. Neuropsychopharmacology 8: 337–344.PubMedGoogle Scholar
  119. Wong, D. T., Bymaster, F. P., Reid, L. R. et al. (1985a).Inhibition of serotonin uptake by optical isomers of fluoxetine. Drug Dev. Res. 6: 397–403.CrossRefGoogle Scholar
  120. Wong, D. T. and Fuller, R. W. (1987).Serotonergic mechanisms in feeding. Int. J. Obesity 11 (suppl 3): 125–133.Google Scholar
  121. Wong, D. T., Fuller, R. W. and Robertson, D.W. (1990a).Fluoxetine and its two enantiomers as selective serotonin uptake inhibitors. Acta Pharm. Nord. 2: 171–180.PubMedGoogle Scholar
  122. Wong, D. T., Horng, J.-S. and Bymaster, F. P. (1975b).dl-N-methyl-3-(o-methoxyphenoxy)-3-phenylpropy-lamine hydrochloride, Lilly 94939, a potent inhibitor for uptake of norepinephrine into rat brain synaptosomes and heart. Life Sci.17: 755–760.PubMedCrossRefGoogle Scholar
  123. Wong, D. T., Horng, J. S. and Fuller, R. W. (1973).Kinetics of serotonin accumulation into synaptosomes of rat brain: Effects of amphetamine and chloroamphetamine. Biochem. Pharmacol. 22: 311–322.PubMedCrossRefGoogle Scholar
  124. Wong, D. T., Horng, J. S., Bymaster, F. P. et al. (1974).A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropyl-amine. Life Sci. 15: 471–479.PubMedCrossRefGoogle Scholar
  125. Wong, D. T. and Murphy, J. M. (1989). Serotonergic mechanisms in alcohol intake, in “Neurobiological and Metabolic Aspects of Alcohol,” G. Y. Sun, Y. H. Wei, P. K. Rudeen etal. (eds.), Humana Press, pp. 133-146.Google Scholar
  126. Wong, D. T., Reid, L. R., Bymaster, F. P. et al. (1985b).Chronic effect of fluoxetine, a selective inhibitor of serotonin uptake, on neurotransmitter receptors. J. Neural Transm. 64: 251–269.PubMedCrossRefGoogle Scholar
  127. Wong, D. T., Reid. L. R., Thompson, D. C. and Robertson, D.W. (1990b). LY210448, a new selective inhibitor of serotonin (5-hydroxytryptamine, 5-HT) uptake and a potential antidepressant and antiobesity drug. Abst. 29th Ann. Meeting, Am. Coll. Neuropsychopharmacology, p. 133.Google Scholar
  128. Wong, D. T., Robertson, D. W., Bymaster, F. P. et al. (1988).LY227942, an inhibitor of serotonin and norepinephrine uptake: biochemical pharmacology of a potential antidepressant drug. Life Sci. 43: 2049–2057.PubMedCrossRefGoogle Scholar
  129. Wong, D. T. and Threlkeld, P.G. (1993). Tricyclic antidepressant drugs exhibit high affinity for serotonin (5-HT)1C receptors. FASEB J. 7: abst. 1530, p. A264.Google Scholar
  130. Wong, D. T., Threlkeld, P. G., Best, K. L. and Bymaster, F. P. (1982).A new inhibitor of norepinephrine uptake devoid of affinity for receptor in rat brain. J. Pharmacol. Exp. Ther. 222: 61–65.PubMedGoogle Scholar
  131. Wong, D. T., Threlkeld, P. G. and Robertson, D. W. (1991).Affinity of fluoxetine, its enantiomers and other inhibitors of serotonin uptake for subtypes of serotonin receptors. Neuropsychopharmacology 5: 43–47.PubMedGoogle Scholar
  132. Yen, T. T., Wong, D. T., and Bemis, K. G. (1987).Reduction of food consumption and body weight of normal and obese mice by chronic treatment with fluoxetine: A serotonin reuptake inhibitor. Drug Dev. Res. 10: 37–45.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • David T. Wong
    • 1
  • Frank P. Bymaster
    • 1
  1. 1.Lilly Research LaboratoriesEli Lilly and Company Lilly Corporate CenterIndianapolisUSA

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