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Psychopharmacology

, Volume 74, Issue 2, pp 101–104 | Cite as

Binding affinity of levomepromazine and two of its major metabolites to central dopamine and α-adrenergic receptors in the rat

  • Svein G. Dahl
  • Håkan Hall
Original Investigations

Abstract

N-Monodesmethyl levomepromazine and levmepromazine sulfoxide have previously been found in higher plasma concentrations than the parent drug in patients who received oral doses of levomepromazine. In the present study levomepromazine, N-monodesmethyl levomepromazine and levomepromazine sulfoxide have been assayed for their binding affinity to rat striatal dopamine receptors and to α-adrenergic receptors in rat cortex, and compared with the potency of chlorpromazine and some of its metabolites in the same systems. Levomepromazine sulfoxide was relatively inactive in the dopamine receptor binding test but much more active in the α-adrenergic receptor binding test, where it had a binding affinity similar to 7-hydroxy chlorpromazine. Levomepromazine and N-monodesmethyl levomepromazine were active in both systems, having a slightly higher potency than chlorpromazine in the α-adrenergic binding test, and a somewhat lower potency than chlorpromazine in the dopamine receptor binding test. The results indicate that N-monodesmethyl levomepromazine may significantly contribute to the antipsychotic effects of levomepromazine while the sulfoxide metabolite lacks neuroleptic potency, and that both metabolites may contribute to the autonomic side-effects of the drug.

Key words

Levomepromazine metabolites Dopamine receptor affinity α-Adrenergic receptor affinity Rat brain 

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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Svein G. Dahl
    • 1
  • Håkan Hall
    • 2
  1. 1.Institute of Medical Biology, Department of PharmacologyUniversity of TromsöTromsöNorway
  2. 2.Astra Research LaboratoriesAstra Läkemedel ABSödertäljeSweden

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