Heterogeneity of benzodiazepine receptors in the central nervous system demonstrated with kenazepine, an alkylating benzodiazepine.
Binding studies using the alkylating benzodiazepine kenazepine strongly suggest the existence of several populations of benzodiazepine receptors in the CNS. Kenazepine reacts noncompetitively and irreversibly with some receptors and competitively (reversibly) with others. Cerebellum contains the largest proportion (approx. 80%) of the noncompetitive type, while hippocampus and cortex contain a preponderance of competitive-type receptors (approx. 80 and 50%, respectively). The Hill coefficients for kenazepine are approx. 0.7 in cortex and cerebellum, and near unity in dorsal hippocampus. Different populations of benzodiazepine receptors may mediate different physiologic and pharmacologic effects in vivo.
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003956:Dialysis; D003975:Diazepam / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011955:Receptors, Drug / Q000145:classification / Q000378:metabolism*; D011963:Receptors, GABA-A
D001570:Benzodiazepinones; D011955:Receptors, Drug; D011963:Receptors, GABA-A; C019439:irazepine; C028261:kenazepine; D003975:Diazepam