Fluoxetine: A case history of its discovery and preclinical development

Expert Opinion on Drug Discovery

Volumn 9, Issue 5, 2014, Pages 567-578

  Perez Caballero, Laura ^a,b   Torres Sanchez, Sonia ^a,b   Bravo, Lidia ^a,b   Mico, Juan Antonio ^a,b   Berrocoso, Esther ^a,b  

^a UNIVERSITY OF CÁDIZ   (Spain)

^b CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE SALUD MENTAL CIBERSAM   (Spain)

Author keywords

Antidepressant; Depression; Fluoxetine; Selective serotonin reuptake inhibitor; Serotonin

Indexed keywords

FLUOXETINE; SEROTONIN UPTAKE INHIBITOR; ANTIDEPRESSANT AGENT;

ANXIETY; COGNITION; DEPRESSION; DRUG EFFECT; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; PRIORITY JOURNAL; REVIEW; ANIMAL; CHEMISTRY; DRUG DEVELOPMENT; DRUG SCREENING; HISTORY; HUMAN;

ANIMALS; ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; FLUOXETINE; HISTORY, 20TH CENTURY; HUMANS;

EID: 84899115583     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2014.907790     Document Type: Review

References (100)

1. Murray CJ, Lopez AD. Evidence-based health policy-lessons from the Global Burden of Disease Study. Science 1996;1;274(5288):740-3 (Pubitemid 26398244)
2. Schildkraut JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 1965;122(5):509-22
3. Bremner JD. Fluoxetine in depressed patients: a comparison with imipramine. J Clin Psychiatry 1984;45(10):414-19 (Pubitemid 14007874)
4. Robertson DW, Jones ND, Swartzendruber JK, et al. Molecular structure of fluoxetine hydrochloride, a highly selective serotonin-uptake inhibitor. J Med Chem 1988;31(1):185-9 (Pubitemid 18027872)
5. Hyttel J. Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs). Int Clin Psychopharmacol 1994;9(Suppl 1):19-26 (Pubitemid 24107713)
6. Wong DT, Bymaster FP, Reid LR, et al. Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain. Neuropsychopharmacology 1993;8(4):337-44 (Pubitemid 23162959)
7. van Harten J. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clin Pharmacokinet 1993;24(3):203-20 (Pubitemid 23094387)
8. Bergstrom RF, Lemberger L, Farid NA, Wolen RL. Clinical pharmacology and pharmacokinetics of fluoxetine: a review. Br J Psychiatry 1988(3):47-50
9. Stevens JC, Wrighton SA. Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450. J Pharmacol Exp Ther 1993;266(2):964-71 (Pubitemid 23318714)
10. Lemberger L, Bergstrom RF, Wolen RL, et al. Fluoxetine: clinical pharmacology and physiologic disposition. J Clin Psychiatry 1985;46(3 Pt 2):14-19 (Pubitemid 15139184)
11. Wong DT, Horng JS, Bymaster FP, et al. A selective inhibitor of serotonin uptake: lilly 110140, 3-(p-trifluoromethylphenoxy)-N-methyl- 3-phenylpropylamine. Life Sci 1974;15(3):471-9
12. Owens MJ, Morgan WN, Plott SJ, Nemeroff CB. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 1997;283(3):1305-22 (Pubitemid 28016506)
13. Wong DT, Bymaster FP, Horng JS, Molloy BB. A new selective inhibitor for uptake of serotonin into synaptosomes of rat brain: 3-(p-trifluoromethylphenoxy) . N-methyl-3-phenylpropylamine. J Pharmacol Exp Ther 1975;193(3):804-11
14. Sanchez C, Hyttel J. Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cell Mol Neurobiol 1999;19(4):467-89 (Pubitemid 29283825)
15. Bymaster FP, Zhang W, Carter PA, et al. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl) 2002;160(4):353-61 (Pubitemid 34253277)
16. Wood MD, Broadhurst AM, Wyllie MG. Examination of the relationship between the uptake system for 5-hydroxytryptamine and the high-affinity [3H]imipramine binding site-I. Inhibition by drugs. Neuropharmacology 1986;25(5):519-25 (Pubitemid 16036369)
17. Koch S, Perry KW, Nelson DL, et al. R-fluoxetine increases extracellular DA, NE, as well as 5-HT in rat prefrontal cortex and hypothalamus: an in vivo microdialysis and receptor binding study. Neuropsychopharmacology 2002;27(6):949-59 (Pubitemid 35447632)
18. Bel N, Artigas F. In vivo effects of the simultaneous blockade of serotonin and norepinephrine transporters on serotonergic function. Microdialysis studies. J Pharmacol Exp Ther 1996;278(3):1064-72 (Pubitemid 27166954)
19. Kreiss DS, Lucki I. Effects of acute and repeated administration of antidepressant drugs on extracellular levels of 5-hydroxytryptamine measured in vivo. J Pharmacol Exp Ther 1995;274(2):866-76
20. Rutter JJ, Auerbach SB. Acute uptake inhibition increases extracellular serotonin in the rat forebrain. J Pharmacol Exp Ther 1993;265(3):1319-24 (Pubitemid 23321035)
21. Sabol KE, Richards JB, Seiden LS. Fluoxetine attenuates the DL-fenfluramine-induced increase in extracellular serotonin as measured by in vivo dialysis. Brain Res 1992;585(1-2):421-4
22. Artigas F. 5-HT and antidepressants: new views from microdialysis studies. Trends Pharmacol Sci 1993;14(7):262 (Pubitemid 23204242)
23. Malagie I, Trillat AC, Jacquot C, Gardier AM. Effects of acute fluoxetine on extracellular serotonin levels in the raphe: an in vivo microdialysis study. Eur J Pharmacol 1995;286(2):213-17
24. Hervas I, Artigas F. Effect of fluoxetine on extracellular 5-hydroxytryptamine in rat brain. Role of 5-HT autoreceptors. Eur J Pharmacol 1998;358(1):9-18 (Pubitemid 28464463)
25. Romero L, Hervas I, Artigas F. The 5-HT1A antagonist WAY-100635 selectively potentiates the presynaptic effects of serotonergic antidepressants in rat brain. Neurosci Lett 1996;219(2):123-6 (Pubitemid 26396330)
26. Palvimaki EP, Roth BL, Majasuo H, et al. Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology (Berl) 1996;126(3):234-40 (Pubitemid 26252760)
27. Gobert A, Rivet JM, Lejeune F, et al. Serotonin(2C) receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic, but not serotonergic, pathways: a combined dialysis and electrophysiological analysis in the rat. Synapse 2000;36(3):205-21 (Pubitemid 30252995)
28. Chen NH, Reith ME. Effects of locally applied cocaine, lidocaine, and various uptake blockers on monoamine transmission in the ventral tegmental area of freely moving rats: a microdialysis study on monoamine interrelationships. J Neurochem 1994;63(5):1701-13
29. Perry KW, Fuller RW. Fluoxetine increases norepinephrine release in rat hypothalamus as measured by tissue levels of MHPG-SO4 and microdialysis in conscious rats. J Neural Transm 1997;104(8-9):953-66 (Pubitemid 27507341)
30. Ichikawa J, Meltzer HY. Effect of antidepressants on striatal and accumbens extracellular dopamine levels. Eur J Pharmacol 1995;281(3):255-61
31. Perry KW, Fuller RW. Extracellular 5-hydroxytryptamine concentration in rat hypothalamus after administration of fluoxetine plus L-5-hydroxytryptophan. J Pharm Pharmacol 1993;45(8):759-61 (Pubitemid 23258699)
32. Invernizzi R, Bramante M, Samanin R. Role of 5-HT1A receptors in the effects of acute chronic fluoxetine on extracellular serotonin in the frontal cortex. Pharmacol Biochem Behav 1996;54(1):143-7
33. Rutter JJ, Gundlah C, Auerbach SB. Increase in extracellular serotonin produced by uptake inhibitors is enhanced after chronic treatment with fluoxetine. Neurosci Lett 1994;171(1-2):183-6 (Pubitemid 24142120)
34. Amargos-Bosch M, Artigas F, Adell A. Effects of acute olanzapine after sustained fluoxetine on extracellular monoamine levels in the rat medial prefrontal cortex. Eur J Pharmacol 2005;516(3):235-8 (Pubitemid 40922743)
35. Tanda G, Frau R, Di Chiara G. Chronic desipramine and fluoxetine differentially affect extracellular dopamine in the rat prefrontal cortex. Psychopharmacology (Berl) 1996;127(2):83-7 (Pubitemid 26298003)
36. Le Poul E, Boni C, Hanoun N, et al. Differential adaptation of brain 5-HT1A and 5-HT1B receptors and 5-HT transporter in rats treated chronically with fluoxetine. Neuropharmacology 2000;39(1):110-22
37. Sharp T, Bramwell SR, Grahame-Smith DG. 5-HT1 agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis. Br J Pharmacol 1989;96(2):283-90 (Pubitemid 19045101)
38. Descarries L, Riad M. Effects of the antidepressant fluoxetine on the subcellular localization of 5-HT1A receptors and SERT. Philos Trans R Soc Lond B Biol Sci 2012;5;367(1601):2416-25
39. Hensler JG. Differential regulation of 5-HT1A receptor-G protein interactions in brain following chronic antidepressant administration. Neuropsychopharmacology 2002;26(5):565-73 (Pubitemid 34260975)
40. Wong DT, Reid LR, Bymaster FP, Threlkeld PG. Chronic effects of fluoxetine, a selective inhibitor of serotonin uptake, on neurotransmitter receptors. J Neural Transm 1985;64(3-4):251-69 (Pubitemid 16174945)
41. Li Q, Muma NA, van de Kar LD. Chronic fluoxetine induces a gradual desensitization of 5-HT1A receptors: reductions in hypothalamic and midbrain Gi and G(o) proteins and in neuroendocrine responses to a 5-HT1A agonist. J Pharmacol Exp Ther 1996;279(2):1035-42
42. Blier P, Chaput Y, de Montigny C. Long-term 5-HT reuptake blockade, but not monoamine oxidase inhibition, decreases the function of terminal 5-HT autoreceptors: an electrophysiological study in the rat brain. Naunyn Schmiedebergs Arch Pharmacol 1988;337(3):246-54
43. Newman ME, Shalom G, Ran A, et al. Chronic fluoxetine-induced desensitization of 5-HT1A and 5-HT1B autoreceptors: regional differences and effects of WAY-100635. Eur J Pharmacol 2004;486(1):25-30 (Pubitemid 38130157)
44. Neumaier JF, Root DC, Hamblin MW. Chronic fluoxetine reduces serotonin transporter mRNA and 5-HT1B mRNA in a sequential manner in the rat dorsal raphe nucleus. Neuropsychopharmacology 1996;15(5):515-22 (Pubitemid 26389875)
45. Gobbi M, Crespi D, Foddi MC, et al. Effects of chronic treatment with fluoxetine and citalopram on 5-HT uptake, 5-HT1B autoreceptors, 5-HT3 and 5-HT4 receptors in rats. Naunyn Schmiedebergs Arch Pharmacol 1997;356(1):22-8 (Pubitemid 27276148)
46. Vidal R, Valdizan EM, Mostany R, et al. Long-term treatment with fluoxetine induces desensitization of 5-HT4 receptor-dependent signalling and functionality in rat brain. J Neurochem 2009;110(3):1120-7
47. Fuxe K, Ogren SO, Agnati LF, et al. Chronic antidepressant treatment and central 5-HT synapses. Neuropharmacology 1983;22(3 Spec No):389-400 (Pubitemid 13152050)
48. Peroutka SJ, Moskowitz MA, Reinhard JF Jr, Snyder SH. Neurotransmitter receptor binding in bovine cerebral microvessels. Science 1980;208(4444):610-12 (Pubitemid 10041978)
49. Zhang W, Perry KW, Wong DT, et al. Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology 2000;23(3):250-62 (Pubitemid 30609659)
50. Covington HE III, Vialou VF, LaPlant Q, et al. Hippocampal-dependent antidepressantlike activity of histone deacetylase inhibition. Neurosci Lett 2011;15;493(3):122-6
51. Baudry A, Mouillet-Richard S, Schneider B, et al. miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science 2010;329(5998):1537-41
52. O'Connor RM, Grenham S, Dinan TG, Cryan JF. microRNAs as novel antidepressant targets: converging effects of ketamine and electroconvulsive shock therapy in the rat hippocampus. Int J Neuropsychopharmacol 2013;16(8):1885-92
53. Oh YS, Gao P, Lee KW, et al. SMARCA3, a chromatin-remodeling factor, is required for p11-dependent antidepressant action. Cell 2013;152(4):831-43
54. Neto FL, Borges G, Torres-Sanchez S, et al. Neurotrophins role in depression neurobiology: a review of basic and clinical evidence. Curr Neuropharmacol 2011;9(4):530-52
55. Coppell AL, Pei Q, Zetterstrom TS. Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacology 2003;44(7):903-10 (Pubitemid 36515026)
56. Khundakar AA, Zetterstrom TS. Biphasic change in BDNF gene expression following antidepressant drug treatment explained by differential transcript regulation. Brain Res 2006;1106(1):12-20 (Pubitemid 44163315)
57. Sairanen M, Lucas G, Ernfors P, et al. Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 2005;25(5):1089-94 (Pubitemid 40268949)
58. Nibuya M, Nestler EJ, Duman RS. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 1996;16(7):2365-72 (Pubitemid 26154346)
59. Song N, Nakagawa S, Izumi T, et al. Involvement of CaMKIV in neurogenic effect with chronic fluoxetine treatment. Int J Neuropsychopharmacol 2013;16(4):803-12
60. Mallei A, Shi B, Mocchetti I. Antidepressant treatments induce the expression of basic fibroblast growth factor in cortical and hippocampal neurons. Mol Pharmacol 2002;61(5):1017-24 (Pubitemid 34441766)
61. Warner-Schmidt JL, Duman RS. VEGF as a potential target for therapeutic intervention in depression. Curr Opin Pharmacol 2008;8(1):14-19 (Pubitemid 351168696)
62. Hajszan T, MacLusky NJ, Leranth C. Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus. Eur J Neurosci 2005;21(5):1299-303 (Pubitemid 40516628)
63. Varea E, Blasco-Ibanez JM, Gomez-Climent MA, et al. Chronic fluoxetine treatment increases the expression of PSA-NCAM in the medial prefrontal cortex. Neuropsychopharmacology 2007;32(4):803-12 (Pubitemid 46426182)
64. Santarelli L, Saxe M, Gross C, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003;301(5634):805-9 (Pubitemid 36962615)
65. McGuirk J, Muscat R, Willner P. Effects of chronically administered fluoxetine and fenfluramine on food intake, body weight and the behavioural satiety sequence. Psychopharmacology (Berl) 1992;106(3):401-7
66. Datla KP, Mitra SK, Bhattacharya SK. Serotonergic modulation of footshock induced aggression in paired rats. Indian J Exp Biol 1991;29(7):631-5
67. Maswood N, Sarkar J, Uphouse L. Modest effects of repeated fluoxetine on estrous cyclicity and sexual behavior in Sprague Dawley female rats. Brain Res 2008;1245:52-60
68. Bravo L, Berrocoso E, Mico JA. Animal models in psychiatry: conceptualization and preclinical models of depression. Eur J Psychiatr 2009;23(Suppl):111-22
69. Nagayama H, Hingtgen JN, Aprison MH. Pre- and postsynaptic serotonergic manipulations in an animal model of depression. Pharmacol Biochem Behav 1980;13(4):575-9 (Pubitemid 10024777)
70. Maj J, Rogoz Z, Skuza G, Sowinska H. The effect of selective inhibitors of noradrenaline and serotonin uptake on reserpine- and apomorphine induced hypothermia in mice. Pol J Pharmacol Pharm 1983;35(1):49-57 (Pubitemid 13036063)
71. Gambarana C, Ghiglieri O, Taddei I, et al. Imipramine and fluoxetine prevent the stress-induced escape deficits in rats through a distinct mechanism of action. Behav Pharmacol 1995;6(1):66-73
72. Detke MJ, Rickels M, Lucki I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology (Berl) 1995;121(1):66-72
73. Cryan JF, Page ME, Lucki I. Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment. Psychopharmacology (Berl) 2005;182(3):335-44 (Pubitemid 41464645)
74. Dulawa SC, Holick KA, Gundersen B, Hen R. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 2004;29(7):1321-30 (Pubitemid 38780655)
75. Griebel G, Cohen C, Perrault G, Sanger DJ. Behavioral effects of acute and chronic fluoxetine in Wistar-Kyoto rats. Physiol Behav 1999;67(3):315-20 (Pubitemid 29469532)
76. Trivedi MH, Rush AJ, Armitage R, et al. Effects of fluoxetine on the polysomnogram in outpatients with major depression. Neuropsychopharmacology 1999;20(5):447-59 (Pubitemid 29123872)
77. Monti JM, Jantos H. A study of the brain structures involved in the acute effects of fluoxetine on REM sleep in the rat. Int J Neuropsychopharmacol 2005;8(1):75-86 (Pubitemid 40388816)
78. Ivarsson M, Paterson LM, Hutson PH. Antidepressants and REM sleep in Wistar-Kyoto and Sprague-Dawley rats. Eur J Pharmacol 2005;522(1-3):63-71 (Pubitemid 41456651)
79. Grippo AJ, Beltz TG, Weiss RM, Johnson AK. The effects of chronic fluoxetine treatment on chronic mild stress-induced cardiovascular changes and anhedonia. Biol Psychiatry 2006;59(4):309-16 (Pubitemid 43238355)
80. Song C, Leonard BE. The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev 2005;29(4-5):627-47 (Pubitemid 40755458)
81. Machado DG, Cunha MP, Neis VB, et al. Fluoxetine reverses depressive-like behaviors and increases hippocampal acetylcholinesterase activity induced by olfactory bulbectomy. Pharmacol Biochem Behav 2012;103(2):220-9
82. Roche M, Harkin A, Kelly JP. Chronic fluoxetine treatment attenuates stressor-induced changes in temperature, heart rate, and neuronal activation in the olfactory bulbectomized rat. Neuropsychopharmacology 2007;32(6):1312-20 (Pubitemid 46788856)
83. Robert G, Drapier D, Bentue-Ferrer D, et al. Acute and chronic anxiogenic-like response to fluoxetine in rats in the elevated plus-maze: modulation by stressful handling. Behav Brain Res 2011;220(2):344-8
84. Silva RC, Brandao ML. Acute and chronic effects of gepirone and fluoxetine in rats tested in the elevated plus-maze: an ethological analysis. Pharmacol Biochem Behav 2000;65(2):209-16 (Pubitemid 30100265)
85. Iniguez SD, Warren BL, Bolanos-Guzman CA. Short- and longterm functional consequences of fluoxetine exposure during adolescence in male rats. Biol Psychiatry 2010;67(11):1057-66
86. Flood JF, Cherkin A. Fluoxetine enhances memory processing in mice. Psychopharmacology (Berl) 1987;93(1):36-43 (Pubitemid 17143724)
87. Meneses A, Hong E. Effect of fluoxetine on learning and memory involves multiple 5-HT systems. Pharmacol Biochem Behav 1995;52(2):341-6
88. Ampuero E, Stehberg J, Gonzalez D, et al. Repetitive fluoxetine treatment affects long-term memories but not learning. Behav Brain Res 2013;247:92-100
89. Sass A, Wortwein G. The effect of subchronic fluoxetine treatment on learning and memory in adolescent rats. Behav Brain Res 2012;228(1):169-75
90. Bangs ME, Petti TA, Janus MD. Fluoxetine-induced memory impairment in an adolescent. J Am Acad Child Adolesc Psychiatry 1994;33(9):1303-6 (Pubitemid 24326576)
91. Altemus M, Glowa JR, Galliven E, et al. Effects of serotonergic agents on food-restriction-induced hyperactivity. Pharmacol Biochem Behav 1996;53(1):123-31
92. Poltronieri SC, Zangrossi H Jr, de Barros Viana M. Antipanic-like effect of serotonin reuptake inhibitors in the elevated T-maze. Behav Brain Res 2003;147(1-2):185-92 (Pubitemid 37491426)
93. Lauzurica N, Garcia-Garcia L, Fuentes JA, Delgado M. Hypophagia and induction of serotonin transporter gene expression in raphe nuclei of male and female rats after short-term fluoxetine treatment. J Physiol Biochem 2013;69(1):69-74
94. Liu M, Wang Y, Wang HM, et al. Fluoxetine attenuates chronic methamphetamine-induced pulmonary arterial remodelling: possible involvement of serotonin transporter and serotonin 1B receptor. Basic Clin Pharmacol Toxicol 2013;112(2):77-82
95. Ho HP, Olsson M, Westberg L, et al. The serotonin reuptake inhibitor fluoxetine reduces sex steroid-related aggression in female rats: an animal model of premenstrual irritability? Neuropsychopharmacology 2001;24(5):502-10 (Pubitemid 32244311)
96. Mico JA, Ardid D, Berrocoso E, Eschalier A. Antidepressants and pain. Trends Pharmacol Sci 2006;27(7):348-54 (Pubitemid 43963184)
97. Chouinard G. A double-blind controlled clinical trial of fluoxetine and amitriptyline in the treatment of outpatients with major depressive disorder. J Clin Psychiatry 1985;46(3 Pt 2):32-7 (Pubitemid 15139187)
98. Turner SM, Jacob RG, Beidel DC, Himmelhoch J. Fluoxetine treatment of obsessive-compulsive disorder. J Clin Psychopharmacol 1985;5(4):207-12 (Pubitemid 15007547)
99. Burrows GD, McIntyre IM, Judd FK, Norman TR. Clinical effects of serotonin reuptake inhibitors in the treatment of depressive illness. J Clin Psychiatry 1988;49(Suppl):18-22
100. Simon GE, VonKorff M, Heiligenstein JH, et al. Initial antidepressant choice in primary care. Effectiveness and cost of fluoxetine vs tricyclic antidepressants. JAMA 1996;275(24):1897-902 (Pubitemid 26196450)