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PMID: 403537 Published · ppublish English Journal Article

Neurochemical characterization of a new potent and selective serotonin uptake inhibitor: Lu 10-171.

Psychopharmacology ·Vol. 51 ·No. 3 ·1977-03-16 ·Pages 225-33

Hyttel J

Abstract

The neurochemical characteristics of a new bicyclic phthalane derivative-Lu10-171 [1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalancarbonitrile; citalopram]-have been investigated. Lu 10-171 and its metabolites were compared with tricyclic thymoleptics in several tests for serotonin (5-HT),noradrenaline (NA), and dopamine (DA) uptake inhibiton in vitro and in vivo. Lu 10-171 is a very potent and completely selective inhibitor of the 5-HT reuptake mechanism, being 2-10 times as active as chlorimipramine. The metabolites of Lu 10-171 show weak 5-HT uptake inhibiting properties. Lu10-171 and its metabolites are devoid of NA uptake inhibiting properties and in this respect they clearly differ from the tricyclic antidepressants, which posses effects both on 5-HT and NA uptake. The inhibition of 5-HT uptake in vitro is competitive and not connected with an increased efflux of 5-HT. Lu10-171 and its metabolites only inhibit DA uptake in extremely high concentrations and in this respect they are even weaker than chlorimipramine and other tricyclic thymoleptics. Like the tricycle thymoleptics, Lu 10-171 is without effect on MAO and does not change the endogenous levels of brain monoamines. Due to the selective action on 5-HT uptake, Lu 10-171 seems to be a valuable tool in studying the role of central 5-HT neurone systems in experimental neuropharmacology as well as in the ethiology of depressive illness.

MeSH Terms
Animals Antidepressive Agents, Tricyclic/pharmacology Biogenic Amines/metabolism Blood Platelets/drug effects,metabolism Brain/metabolism,ultrastructure Brain Chemistry/drug effects Corpus Striatum/metabolism,ultrastructure Depression, Chemical Dogs Dopamine/metabolism Female In Vitro Techniques Male Mice Microsomes/drug effects,enzymology Microsomes, Liver/drug effects,enzymology Monoamine Oxidase Inhibitors Myocardium/metabolism Nitriles/pharmacology Norepinephrine/metabolism Propylamines/pharmacology Rabbits Rats Serotonin/blood,metabolism Synaptosomes/drug effects,metabolism
Chemicals
Antidepressive Agents, Tricyclic Biogenic Amines Monoamine Oxidase Inhibitors Nitriles Propylamines Serotonin Dopamine Norepinephrine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Hyttel J
References (39)
39 references, click to expand
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Article Info
Journal
Psychopharmacology
Abbr.
Psychopharmacology (Berl)
ISSN
0033-3158
DOI
10.1007/BF00431629
Published
1977-03-16
Pages
225-33
Language
English
Region
Germany
NLM ID
7608025
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00431629 View journal details
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