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

Psychopharmacology (Berl). 1977 Mar 16;51(3):225-33. doi: 10.1007/BF00431629.

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
  • Blood Platelets / metabolism
  • Brain / metabolism
  • Brain / ultrastructure
  • Brain Chemistry / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / ultrastructure
  • Depression, Chemical
  • Dogs
  • Dopamine / metabolism
  • Female
  • In Vitro Techniques
  • Male
  • Mice
  • Microsomes / drug effects
  • Microsomes / enzymology
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Monoamine Oxidase Inhibitors
  • Myocardium / metabolism
  • Nitriles / pharmacology*
  • Norepinephrine / metabolism
  • Propylamines / pharmacology*
  • Rabbits
  • Rats
  • Serotonin / blood
  • Serotonin / metabolism*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism

Substances

  • Antidepressive Agents, Tricyclic
  • Biogenic Amines
  • Monoamine Oxidase Inhibitors
  • Nitriles
  • Propylamines
  • Serotonin
  • Dopamine
  • Norepinephrine