title: Trimipramine: pharmacological reevaluation and comparison with clozapine.
abstract: Trimipramine has been reported to differ from other typical tricyclic antidepressant drugs in several aspects, for instance it does not inhibit neuronal transmitter uptake and does not cause down-regulation of beta-adrenoceptors. Moreover, it may possess antipsychotic activity in schizophrenic patients. In the present investigation it was found that trimipramine did not alter the electrically-induced release of [3H]noradrenaline and [3H]5-hydroxytryptamine, from slices of the cerebral cortex of the rat, in concentrations of less than 1 microM. It did not antagonize the inhibitory effect of noradrenaline and 5-hydroxytryptamine on the release of transmitter, mediated by presynaptic autoreceptors. In radioligand binding studies, D,L-trimipramine showed fairly high affinities (KI 10-60 nM) for some dopamine (DA), noradrenaline and 5-hydroxytryptamine (5-HT) receptor subtypes (5-HT2 receptors = alpha 1A/B-adrenoceptors greater than or equal to D2 receptors), intermediate affinities (300-550 nM) for D1 receptors, alpha 2B-adrenoceptors and 5-HT1C receptors but only low affinities (greater than 1000 nM) for alpha 2A-adrenoceptors, 5-HT1A, 5-HT1D and 5-HT3 receptors. It may thus be classified as an atypical neuroleptic drug. Especially, its affinities for dopamine receptors, alpha 1-adrenoceptors and 5-HT2 receptors closely resembled the values measured for clozapine. The L-enantiomer of trimipramine showed higher affinities for these binding sites than D-trimipramine. The present findings may explain the mechanism of the potential antipsychotic action but not the antidepressant effect of trimipramine.
authors.affiliation: Institut für Pharmakologie, Universitätsklinikum Essen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Gross
authors.forename: X
authors.initials: X
authors.lastname: Xin
authors.forename: M
authors.initials: M
authors.lastname: Gastpar
mesh_terms: D000818:Animals; D003024:Clozapine / Q000494:pharmacology*; D004558:Electric Stimulation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014299:Trimipramine / Q000494:pharmacology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D014299:Trimipramine; D003024:Clozapine; D009638:Norepinephrine