In:
British Journal of Psychiatry, Royal College of Psychiatrists, Vol. 153, No. S3 ( 1988-09), p. 40-46
Abstract:
The chemical structure of fluoxetine, (±)- N -methyl-3-phenyl-3-[(α,α,α-trifluoro- p -tolyl)oxy]propylamine, as shown in Fig. 1, lacks the three-fused ring system contained in tricyclic antidepressant drugs (TCAs) such as imipramine and amitriptyline. The p- trifluoromethyl substituent on the phenoxy ring of fluoxetine is an important determinant of its potency and its specificity as a serotonin-uptake inhibitor, e.g. the analogue having an o-trifluoromethyl substituent on that ring is only about one-hundredth as potent as fluoxetine in inhibiting serotonin uptake (Wong et al , 1975 a ). Nisoxetine (Wong et al , 1975 b ) and tomoxetine (Wong et al , 1982) are analogues differing from fluoxetine only in having an o -methoxy or an o -methyl substituent respectively, in place of the p -trifluoromethyl substituent on the phenoxy ring. Nisoxetine (LY94939) and tomoxetine (LY 139603) are potent and highly selective inhibitors of norepinephrine uptake (Wong et al , 1975 b , 1982), differing strikingly from fluoxetine in specificity of uptake inhibition. Fluoxetine has been shown to be a potent and selective inhibitor of serotonin uptake in laboratory animals; it is orally effective and has a long duration of action. This compound has been a valuable pharmacological tool to study the mechanisms of serotonergic neurotransmission and physiological functions of brain serotonin neurons (Fuller & Wong, 1977; Wong et al , 1985a; Fuller & Wong, 1987). The present paper summarises some of the pre-clinical studies which have characterised fluoxetine as a selective inhibitor of serotonin uptake.
Type of Medium:
Online Resource
ISSN:
0007-1250
,
1472-1465
DOI:
10.1192/S0007125000297274
Language:
English
Publisher:
Royal College of Psychiatrists
Publication Date:
1988
detail.hit.zdb_id:
2021500-9
