Differential mediation of the anticonvulsant effects of carbamazepine and diazepam.
Possible mechanisms of action of carbamazepine and diazepam on amygdala-kindled seizures were studied using compounds acting at the central and "peripheral-type" benzodiazepine binding sites. Ro-15-1788, a selective antagonist at the central benzodiazepine site, blocked the anticonvulsant effect of diazepam, but not of carbamazepine. In contrast, Ro5-4864, which acts at the "peripheral-type" benzodiazepine site, blocked the anticonvulsant effect of carbamazepine, but not of diazepam. The effect of Ro5-4864 was itself reversed by PK-11195, a compound that displaces Ro5-4864 binding in vitro and in vivo. These data indicate that the anticonvulsant effects of carbamazepine and diazepam on amygdala-kindled seizures are differentially mediated and suggest that the "peripheral-type" benzodiazepine binding site is functionally involved in the anticonvulsant effect of carbamazepine.
Weiss
S R
SR
Post
R M
RM
Patel
J
J
Marangos
P J
PJ
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants; D001570:Benzodiazepinones / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D007546:Isoquinolines / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism
D000927:Anticonvulsants; D001570:Benzodiazepinones; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D002220:Carbamazepine; D003975:Diazepam; C037850:PK 11195