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

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Abstract
The neurochemical characteristics of a new bicyclic phthalane derivative — Lu 10-171 [1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalan-carbonitrile; 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 inhibition 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. Lu 10-171 and its metabolites are devoid of NA uptake inhibiting properties and in this respect they clearly differ from the tricyclic anti-depressants, which possess 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. Lu 10-171 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 tri-cyclic 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.