Is Ro15-1788 a partial agonist at benzodiazepine receptors?
The ability of the imidazodiazepine derivative Ro15-1788, a potent and specific displacer of benzodiazepine binding, to induce and reduce benzodiazepine-like activity has been evaluated against the convulsant activity evoked by leptazol, bicuculline and the convulsant benzodiazepine Ro5-3663, in mice. Ro15-1788 (10-50 mg/kg) produced a dose dependent reduction in the activity of all 3 convulsants (significant at 50 mg/kg), when they were given at just maximal convulsant doses, but this effect was lost with supramaximal doses of the convulsants, as used in other reported experiments. In addition to this weak benzodiazepine-like activity, Ro15-1788 also reduced the anticonvulsant activity of diazepam and a triazolopyridazine derivative but not that of phenobarbitone. This effect was more marked at 10 than 25 or 50 mg/kg Ro15-1788. It is concluded that although Ro15-1788 has a specific effect on drugs acting at the benzodiazepine receptor it should be classified as a weak partial agonist rather than an antagonist at this site.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010634:Phenobarbital / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A
D001570:Benzodiazepinones; D003292:Convulsants; D011724:Pyridazines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005442:Flumazenil; C021604:CL 218872; D003975:Diazepam; D001640:Bicuculline; D010634:Phenobarbital