Ro 15-4513, a partial inverse agonist for benzodiazepine recognition sites, has proconflict and proconvulsant effects in the rat.
The present report describes the effects of Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-(1,5-a) (1,4)-benzodiazepine-3-carboxylate) in the conflict test, on convulsions induced by isoniazid and DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) and on the binding of [3H]gamma-aminobutyric acid ([3H]GABA) to rat brain membrane preparations. Ro 15-4513 produced a dose-dependent proconflict effect that was prevented by the administration of the benzodiazepine antagonist, Ro 15-1788. In addition, Ro 15-4513 was not convulsant per se but enhanced the convulsions produced by isoniazid and completely blocked the convulsions induced by the full inverse agonist, DMCM. In vitro, Ro 15-4513, like ethyl-beta-carboline-3-carboxylate (beta CCE), antagonized the increase in [3H]GABA binding induced by diazepam. The results indicate that Ro 15-4513 is anxiogenic and interacts with benzodiazepine recognition sites as a partial inverse agonist.
Corda
M G
MG
Department of Experimental Biology, University of Cagliari, Italy.
Giorgi
O
O
Longoni
B
B
Biggio
G
G
D000818:Animals; D001386:Azides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D003220:Conflict, Psychological; D003292:Convulsants; D005442:Flumazenil / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D011678:Punishment; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects
D001386:Azides; D002243:Carbolines; D003292:Convulsants; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil; C042957:Ro 15-4513; C036150:beta-carboline-3-carboxylic acid methyl ester; D010424:Pentobarbital; D007538:Isoniazid