Binding affinity of levomepromazine and two of its major metabolites of central dopamine and alpha-adrenergic receptors in the rat.
N-Monodesmethyl levomepromazine and levomepromazine 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 alpha-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 alpha-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 alpha-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.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D004146:Dioxanes; D008297:Male; D008728:Methotrimeprazine / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D008728:Methotrimeprazine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane