3H-Spiroperidol binding to dopamine receptors in rat striatal membranes: influence of loxapine and its hydroxylated metabolites.
The effects of loxapine and its hydroxylated metabolites 7-hydroxyloxapine and 8-hydroxyloxapine on 3H-spiroperidol binding to rat striatal membranes were investigated. Whereas 7-hydroxyloxapine and loxapine displayed strong affinities for 3H-spiroperidol binding sites, 8-hydroxyloxapine was essentially inactive. The potency of 7-hydroxyloxapine to displace 3H-spiroperidol is 1.5 times and 8 times those of haloperidol and chlorpromazine, respectively. These results suggest that the combined effects of loxapine and 7-hydroxyloxapine on the postsynaptic dopamine receptors in the brain may explain the clinical efficacy of loxapine in the treatment of schizophrenia.
D000818:Animals; D002090:Butyrophenones / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D003989:Dibenzoxazepines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D006900:Hydroxylation; D066298:In Vitro Techniques; D008152:Loxapine / Q000494:pharmacology*; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism*
D002090:Butyrophenones; D003989:Dibenzoxazepines; D011954:Receptors, Dopamine; D013134:Spiperone; D003024:Clozapine; D006220:Haloperidol; D008152:Loxapine; D002746:Chlorpromazine