In vitro interaction of premazepam with benzodiazepine receptors in rat brain regions.
Premazepam (PRZ) in vitro competitively displaced 3H-diazepam (DIA), 3H-flunitrazepam (FLU) and 3H-RO 15-1788 from their binding sites on rat brain synaptosomes, with a potency intermediate to other benzodiazepines (BDZs), and Hill coefficients near 1 in different brain regions. Incubation at 37 degrees C reduced premazepam's affinity for BDZ receptors to a lower extent than other benzodiazepines and had no effect on the Hill coefficient. The IC50 of PRZ on 3H-RO 15-1788 and 3H-FLU binding was markedly reduced by GABA in rat cortex, like those of reference classical BDZs, but was GABA-independent in the cerebellum. The IC50 of the BDZ antagonist, RO 15-1788 was unaffected by GABA in both brain areas. The possibility that PRZ behaves as a partial agonist in the cortex and as an antagonist in the cerebellum is discussed.
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001569:Benzodiazepines / Q000378:metabolism*; D001570:Benzodiazepinones / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003292:Convulsants / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D005442:Flumazenil; D005445:Flunitrazepam / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013574:Synaptosomes / Q000378:metabolism*; D013816:Thermodynamics
D001381:Azepines; D001570:Benzodiazepinones; D003292:Convulsants; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil; D005445:Flunitrazepam; C041286:premazepam; D003975:Diazepam