Case history: The discovery of fluoxetine hydrochloride (Prozac)

Nature Reviews Drug Discovery

Volumn 4, Issue 9, 2005, Pages 764-774

  Wong, David T ^a   Perry, Kenneth W ^b   Bymaster, Frank P ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 HYDROXYTRYPTOPHAN; AMITRIPTYLINE; ANTIDEPRESSANT AGENT; APOMORPHINE; CITALOPRAM; CLOMIPRAMINE; DESIPRAMINE; DIPHENHYDRAMINE; FLUOXETINE; IMIPRAMINE; LY 82816; LY 86032; MONOAMINE OXIDASE INHIBITOR; NISOXETINE; NORCLOMIPRAMINE; NORFLUOXETINE; NORTRIPTYLINE; PAROXETINE; PROBENECID; SEROTONIN; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRICYCLIC ANTIDEPRESSANT AGENT; UNCLASSIFIED DRUG; ZIMELDINE;

ANOREXIA NERVOSA; ANXIETY; BLURRED VISION; BULIMIA; CONSTIPATION; DEPRESSION; DROWSINESS; DRUG APPROVAL; DRUG MECHANISM; DRUG RESPONSE; DRUG SOLUBILITY; DRUG STRUCTURE; DYSPHORIA; FLU LIKE SYNDROME; GENERALIZED ANXIETY DISORDER; HEART MUSCLE CONDUCTION DISTURBANCE; HUMAN; INSOMNIA; MAJOR DEPRESSION; NAUSEA; NEUROTRANSMISSION; NONHUMAN; OBSESSIVE COMPULSIVE DISORDER; ORTHOSTATIC HYPOTENSION; PANIC; PRIORITY JOURNAL; REVIEW; SEDATION; SEROTONIN UPTAKE; SEXUAL DYSFUNCTION; SIDE EFFECT; STRUCTURE ACTIVITY RELATION; SYNAPSE; SYNAPTOSOME; VOMITING; XEROSTOMIA; DRUG DESIGN; DRUG INDUSTRY; HISTORY; METHODOLOGY;

DEPRESSION; DRUG APPROVAL; DRUG DESIGN; DRUG INDUSTRY; FLUOXETINE; HISTORY, 20TH CENTURY; HUMANS;

EID: 26044482076     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ajo.2005.02.011     Document Type: Review

References (89)

1. Wong, D. T., Horng, J. S., Bymaster, F. P., Hauser, K. L. & Molloy, B. B. A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine. Life Sci. 15, 471-479 (1974).
2. Fuller, R. W., Perry, K. W. & Molloy, B. B. Effect of an uptake inhibitor on serotonin metabolism in rat brain: Studies with 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine (Lilly 110140). Life Sci. 15, 1161-1171 (1974).
3. Fuller, R. W. & Wong, D. T. Inhibition of serotonin uptake. Fed. Proc. Fed. Am. Soc. Exp. Blol. 36, 2154-2158 (1977).
4. Fuller, R. W., Wong, D. T. & Robertson, D. W. Fluoxetine, a selective inhibitor of serotonin uptake. Med. Res. Rev. 11, 17-34 (1991).
5. Wong, D. T., Bymaster, F. P. & Engleman, E. A. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug (in US): Twenty years since its first publication. Life Sci. 57, 411-441 (1995).
6. Stark, P. & Hardison, C. D. A review of multicenter controlled studies of fluoxetine vs imipramine and placebo in outpatients with major depressive disorder. J. Clin. Psychiatry 46, 53-58 (1985).
7. Boyer, W. F. & Feighner, J. P. in Perspectives in Psychiatry, Volume 1: Selective Serotonin Re-uptake Inhibitors (eds Feighner, J. P. & Boyer, W. F.) 89-108 (Wiley, Chichester, England, 1991).
8. Stokes, P. Fluoxetine: A five-year review. Clin. Ther. 15, 216-243 (1993).
9. Molloy, B. B., Wong, D. T. & Fuller, R. W. The discovery of fluoxetine. Pharmaceutical News 1, 6-10 (1994).
10. Bourne, G. H. The Structure and Function of Nervous Tissue, III: Biochemistry and Disease (Academic Press, New York, 1969).
11. Gray, E. G. & Whittaker, V. P. The isolation of nerve endings from brain: An electron-microscopic study of cell fragments derived by homogenization and centrifugation. J. Anal. 96, 79-88 (1962).
12. Whittaker, V. P. in The Structure and Function of Nervous Tissue, III: Biochemistry and Disease (ed. Bourne, G. H.) 1-24 (Academic Press, New York, 1969).
13. Wong, D. T., Horng, J. S., Hamill, R. L. & Lardy, H. A. Effect of a new monocarboxylic acid antibiotic, A204, on the monovalent cation permeability of rat liver mitochondria. Biochem. Pharmacol. 20, 3169-3177 (1971).
14. Wong, D. T., Wilkinson, J. R., Hamill, R. L. & Horng, J. S. Effects of antibiotic ionophore, A23187, on oxidative phosphorylation and calcium transport of liver mitochondria. Arch. Biochem. Biophys. 156, 578-585 (1973).
15. Wong, D. T., Van Frank, R. M., Horng, J. S. & Fuller, R. W. Accumulation of amphetamine and p-chloroamphetamine into synaptosomes of rat brain. J. Pharm. Pharmacol. 24, 171-173 (1972).
16. Page, I. in Serotonin and the Brain (ed. Bourne, G. H.) 289-307 (Academic Press, New York, 1969).
17. Rapport, M. M., Green, A. A. & Page, I. H. Crystalline serotonin. Science 108, 329-330 (1948).
18. Twarog, B. M. & Page, I. H. Serotonin content of some mammalian tissues and urine and a method for its determination. Am. J. Physiol. 175, 157-161 (1953).
19. Weil-Malherbe, H. & Szara, S. I. in The Biochemistry of Functional and Experimental Psychoses 5-16. (Thomas, Springfield, Illinois, 1971).
20. Dahlstrom, A. & Fuxe, K. Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand. 62 (Suppl. 232), 1-55 (1964).
21. Fuxe, K., Hokfelt, T. & Ungerstedt, U. Localization of indol-alkylamines in CNS. Adv. Pharmacol. 6A, 235-251 (1968).
22. Lindbrink, P., Jonsson, G. & Fuxe, K. The effect of imipramine-like drugs and antihistamine drugs on uptake mechanisms in the central noradrenaline and 5-hydroxy-tryptamine neurons. Neuropharmacology 10, 521-536 (1971).
23. Wong, D. T., Horng, J. S. & Fuller, R. W. Kinetics of serotonin accumulation into synaptosomes of rat brain-effects of amphetamine and chloroamphetamines. Biochem. Pharmacol. 22, 311-322 (1973).
24. Wong, D. T., Horng, J. S. & Bymaster, F. P. DL-N-methyl 3-(o-methoxyphenoxy)-3-phenylpropylamine hydrochloride, Lilly 94939, a potent inhibitor for uptake of norepinephrine into rat brain synaptosomes and heart. Life Sci. 17, 755-760 (1975).
25. Wong, D. T. & Bymaster, F. P. Effect of nisoxetine on uptake of catecholamines in synaptosomes isolated from discrete regions of rat brain. Biochem. Pharmacol. 25, 1979-1983 (1976).
26. Bunney, W. E. Jr. & Davis, J. M. Norepinephrine in depressive reactions. A review. Arch. Gen. Psychiatry 13, 483-494 (1965).
27. Schildkraut, J. J. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am. J. Psychiatry 122, 509-522 (1965).
28. Axelrod, J. Noradrenaline: Fate and control of its biosynthesis. Science 173, 598-606 (1971).
29. Weil-Malherbe, H. & Szara, S. I. in The Biochemistry of Functional and Experimental Psychoses 57-76 (Thomas, Springfield, Illinois, 1971).
30. Gillette, J. R., Dingell, J. V., Sulser, F., Kuntzman, R. & Brodie, B. B. Isolation from rat brain of a metabolic product, desmethylimipramine, that mediates the antidepressant activity of imipramine (Tofranil). Experientia (Basel) 17, 417-416 (1961)
31. Hertting, G., Axelrod, J. & Whitby, L. G., Effect of drugs on the uptake and metabolism of 3H-norepinephrine. J. Pharmacol. Exp. Ther. 134, 146-153 (1961).
32. Carlsson, A. Structural specificity for inhibition of [3H]-5-hydroxytryptamine uptake by cerebral slices. J. Pharm. Pharmac. 22, 729-732 (1970).
33. Carlsson, A., Fuxe, K. & Ungerstedt, U. The effect of imipramine on central 5-hydroxytryptamine neurons. J. Pharm. Pharmacol. 20, 150-151 (1968).
34. Carlsson, A., Corrodi, H., Fuxe, K. & Hokfelt, T. Effects of some antidepressant drugs on the depletion of intraneuronal brain catecholamine stores caused by 4,α-dimethyl-metatyramine. Eur. J. Pharmacol. 5, 367-373 (1969).
35. Carlsson, A., Corrodi, H., Fuxe, K. & Hokfelt, T. Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-α-ethyl-meta-tyramine. Eur. J. Pharmacol. 5, 357-366 (1969).
36. Carlsson, A., Fuxe, K., Hamberger, B. & Lindqvist, M. 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 (1966).
37. Shaw, D. M., Camps, F. E. & Eccleston, E. G. 5-hydroxytryptamine in the hind-brain of depressive suicides. Br. J. Psychiatry 113, 1407-1411 (1967).
38. Bourne, H. R. et al. Noradrenaline, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in hindbrains of suicidal patients. Lancet 2, 805-808 (1968).
39. Pare, C. M., Yeung, D. P., Price, K. & Stacey, R. S. 5-hydroxytryptamine, noradrenaline and dopamine in brain stem, hypothalamus and caudate nucleus of control and of patients committing suicide by coal-gas poisoning. Lancet 2, 133-135 (1969).
40. Coppen, A., Shaw, D. M. & Farrell, J. P. Potentiation of the antidepressive effect of a monoamine oxidase inhibitor by tryptophan. Lancet 1, 79-81 (1963).
41. Pare, C. M. B. Potentiation of monoamine oxidase inhibitors by tryptophan. Lancet II 35, 527-528 (1963).
42. Kline, N. S. & Sack, W. Relief of depression within one day using an M. A. O. inhibitor and intravenous 5-HTP. Am. J. Psychiatry 120, 274-275 (1963).
43. Shaskan, E. G. & Snyder, S. H. Kinetics of serotonin accumulation into slices from rat brain: Relationship to catecholamine uptake. J. Pharm. Exp. Ther. 175, 404-418 (1970).
44. Blackburn, K. J., French, P. C. & Merrills, R. J. 5-hydroxytryptamine uptake by rat brain in vitro. Life Sci. 6, 1653-1663 (1967).
45. Ross, S. B. & Renyi, A. L. Inhibition of the uptake of tritiated 5-hydroxytryptamine in brain tissue. Eur. J. Pharm. 7, 270-277 (1969).
46. 3H]-dopamine uptake in rat brain homogenates. J. Pharmacol. Exp. Ther. 165, 78-86 (1969).
47. Slater, I. H., Rathbun, R. C. & Kattau, R. Role of 5-hydroxytryptaminergic and adrenergic mechanism in antagonism of reserpine-induced hypothermia in mice. J. Pharm. Pharmacol. 31, 108-110 (1979).
48. Wong, D. T. & Bymaster, F. P. in Neurochemistry in Clinical Application (eds Tang, L. & Tang, S.) 77-95 (Plenum, New York, 1995).
49. Wong, D. T., Bymaster, F. P., Horng, J. S. & Molloy, B. B. 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine (Lilly 110140), a selective inhibitor of serotonin uptake into synaptosomes of rat brain. Fed. Proc. 33, 296 (1974).
50. Wong, D. T., Bymaster, F. P., Horng, J. S. & Molloy, B. B. A new selective inhibitor for uptake of serotonin into synaptosomes of rat brain: 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine. J. Pharmacol. Exp. Ther. 193, 804-811 (1975).
51. Horng, J. S., Bymaster, F. P. & Wong, D. T. Effects of compound, Lilly 110140, a specific inhibitor of serotonin uptake on transport of monoamines in peripheral tissues of rat. Fed. Proc. 33, 560 (1974).
52. Horng, J. S. & Wong, D. T. Effects of serotonin uptake inhibitor, Lilly 110140, on transport of serotonin in rat and human blood platelets. Biochem. Pharmacol. 25, 865-867 (1976).
53. Fuller, R. W. & Perry, K. W. Blockade of 4-chloroamphetamine-induced depletion of brain serotonin by 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine hydrochloride (Lilly 110140), a selective inhibitor of uptake by serotonin neurons. Fed. Proc. 33, 255 (1974).
54. Wong, D. T. & Bymaster, F. P. 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. Path. Pharmacol. 15, 221-231 (1976).
55. Fuller, R. W. Kinetic studies and effects in vivo of a new monoamine oxidase inhibitor. N-[2-(o-chlorophenoxy)-ethyl]-cyclopropylamine. Biochem. Pharmacol. 17, 2097-2106 (1968).
56. Mills, J., Kattau, R., Slater, I. H. & Fuller, R. W. N-substituted cyclopropylamines as monoamine oxidase inhibitors. Structure-activity relationships. Dopa potentiation in mice and in vitro inhibition of kynuramine oxidation. J. Med. Chem. 11, 95-97 (1968).
57. Fuller, R. W., Hines, C. W. & Mills J. Lowering of brain serotonin level by chloramphetamines. Biochem. Pharmacol. 14, 483-488 (1965).
58. Fuller, R. W. & Hines, C. W. Tissue levels of chloroamphetamines in rats and mice. J. Pharm. Sci. 56, 302-303 (1967).
59. Fuller, R. W. & Hines, C. W. Inhibition by p-chloroamphetamine of the conversion of 5-hydroxytryptamine to 5-hydroxyindoleacetic acid in rat brain. J. Pharm. Pharmacol. 22, 634-635 (1970).
60. Meek, J. L., Fuxe, K. & Carlsson, A. Blockade of p-chloromethamphetamine induced 5-hydroxytryptamine depletion by chlorimipramine, chlorpheniramine and meperidine. Biochem. Pharmacol. 20, 707-709 (1971).
61. Carlsson, A., Jonason, J., Lindqvist, M. & Fuxe, K. Demonstration of extraneuronal 5-hydroxytryptamine accumulation in brain following membrane-pump blockade by chlorimipramine. Brain Res. 12, 456-460 (1969).
62. Fuller, R. W., Perry, K. W., Snoddy H. D. & Molloy, B. B. Comparison of the specificity of 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine and chlorimipramine as amine uptake inhibitors in mice. Eur. J. Pharmacol. 28, 233-236 (1974).
63. Da Prada, M. & Pletscher, A. On the mechanism of chlorpromazine-induced changes of cerebral homovanillic acid levels. J. Pharm. Pharmacol. 18, 628-630 (1966).
64. Miller, F. P., Cox, R. H., Snodgrass, W. R. & Maickel, R. P. Comparative effects of p-chloroamphetamine and p-chloro-N-methylamphetamine on rat brain norepinephrine, serotonin and 5-hydroxyindole-3-acetic acid. Biochem. Pharmacol. 19, 435-442 (1970).
65. Perry, K. W. & Fuller, R. W. Effect of 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine HCl (Lilly 110140), a specific inhibitor of serotonin uptake, on 5-hydroxyindole levels and turnover in rats. Fed. Proc. 33, 560 (1974).
66. Bymaster, F. P. & Wong, D. T. Effect of Lily 110140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine on synthesis of [3H]-serotonin from [3H]-tryptophan in rat brain. Pharmacologist 16, 244 (1974).
67. Clemens, J. A., Sawyer, B. D. & Cerimele, B. Further evidence that serotonin is a neurotransmitter involved in the control of prolactin secretion. Endocrinology 100, 692-698 (1977).
68. Perry, K. W. & Fuller, R. W. Effect of fluoxetine on serotonin and dopamine concentration in microdialysis fluid from rat striatum. Life Sci. 50, 1683-1690 (1992).
69. Fuller, R. W., Snoddy, H. D. & Molloy B. B. Potentiation of the L-5-hydroxytryptophan-induced elevation of plasma corticosterone levels in rats by a specific inhibitor of serotonin uptake. Res. Comm. Chem. Path. Pharmacol. 10, 193-196 (1975).
70. Parli, C. J. & Hick, J. In vivo demethylation of Lilly 110140: 3(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine to an active metabolite, Lilly 103947. Fed. Proc. 33, 560 (1974).
71. Fuller, R. W., Perry, K. W. & Molloy, B. B. Effect of 3-(p-trifluoromethylphenoxy). N.N.methyl-3-phenylpropylamine on the depletion of brain serotonin by 4-chloroamphetamine. J. Pharmacol. Exp. Ther. 193. 793-803 (1975).
72. Asberg, M., Bertilsson, L., Tuck, D., Cronholm, B. & Sjoqvist, F. Indoleamine metabolites in the cerebrospinal fluid of depressed patients before and during treatment with nortriptyline. Clin. Pharmacol. Ther. 14, 277-286 (1973).
73. Lemberger, L. et al. Pharmacologic effects in man of a specific serotonin-reuptake inhibitor. Science 199, 436-437 (1978).
74. Lemberger, L. et al. Fluoxetine, a selective serotonin uptake inhibitor. Clin. Pharmacol. Ther. 23, 421-429 (1978).
75. Wong, D. T., Bymaster, F. P., Reid, L. R. & Threlkeld, P. G. Fluoxetine and two other serotonin uptake inhibitors without affinity for neuronal receptors. Biochem. Pharmacol. 32, 1287-1293 (1983).
76. Montgomery, S. A. Development of new treatments for depression, J. Clin. Psychiatry 46, 3-6 (1985).
77. Wernicke, J. F. The side effect profile and safety of fluoxetine. J. Clin. Psychiatry 40, 59-67 (1985).
78. Beasley, C. M. Jr, Nilsson, M. E., Koke, S. C. & Gonzales, J. S. Efficacy, adverse events, and treatment discontinuations in fluoxetine clinical studies of major depression: A meta-analysis of the 20-mg/day dose. J. Clin. Psychiatry 61, 722-728 (2000).
79. Bengtsson, B. O., Wiholm, B. E., Myrhed, M. & Walinder, J. Adverse experiences during treatment with zimelidine on special licence in Sweden. Int. Clin. Pharmacol. 9, 55-61 (1994).
80. Davidson, J. R. & Meltzer-Brody, S. E. The underrecognition and undertreatment of depression: What is the breadth and depth of the problem? J. Clin. Psychiatry 60 (Suppl. 7), 4-9 (1999).
81. Ustun, T. B., Ayuso-Mateos, J. L., Chatterji, S., Mathers, C. & Murray, C. J. Global burden of depressive disorders in the year 2000. Br. J. Psychiatry 184, 386-392 (2004).
82. Arias, E. et al. Deaths: Final data for 2001. National Vital Statistics Reports (CDC) 52, 1-116 (2003).
83. Stokes, P. E. & Holtz, A. Fluoxetine tenth anniversary update: The progress continues. Clin Ther. 19, 1135-1250 (1997).
84. Stokes, P. E. Ten years of fluoxetine. Depress Anxiety 8 (Suppl. 1), 1-4 (1998).
85. Tranter, R., O'Donovan, C., Chandarana, P. & Kennedy, S. Prevalence and outcome of partial remission in depression. J. Psychiatry Neurosci. 27, 241-247 (2002).
86. Mulrow, C. D. et al. Efficacy of newer medications for treating depression in primary care patients. Am. J. Med. 108, 54-64 (2000).
87. Wernicke, J. F. Safety and side effect profile of fluoxetine. Expert Opin. Drug Saf. 3, 495-504 (2004).
88. Stevens, J. C. & Wrighton, S. A. Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450. J. Phammacol. Exp. Ther. 266, 964-971 (1993).
89. Page, I. H. & McCubbin, J. W. Serotonin or tenure for the pharmacologist. Circulation 14, 161 (1956).