Are "peripheral-type" binding sites for benzodiazepines in brain related to the convulsant actions of Ro 5-4864?
Previous studies have shown that Ro 5-4864 is a potent convulsant. Investigation of a series of compounds structurally related to Ro-4864 revealed a good correlation (r = .93, p less than 0.01) between their potencies as convulsants and their abilities to displace [35S]t-butylbicyclophosphorothionate from sites associated with the chloride ionophore. In contrast, there appears to be no direct relationship between the convulsant potencies of these compounds and their affinities for "peripheral-type" binding sites for benzodiazepines. These data suggest that "peripheral-type" binding sites for benzodiazepines are not directly involved in the convulsant actions of Ro 5-4864 and related compounds nonetheless, several lines of evidence suggest that "peripheral-type" binding sites for benzodiazepines may be indirectly involved in the convulsant properties of Ro 5-4864.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001570:Benzodiazepinones; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; C037476:tert-butylbicyclophosphorothionate