Evidence for distinct benzodiazepine receptors for anticonvulsant and sedative actions: implications for the treatment of temporal lobe epilepsy.

An imidazobenzodiazepine, Ro15-1788, has anticonvulsant effects in the kindling model for epilepsy. Ro15-1788 reverses the sedative actions of diazepam (3 mg/kg i.p.) but does not reverse the anticonvulsant effects. The anticonvulsant effects of Ro15-1788 are prevented by the pyrazoloquinolinone CGS-8216 which interacts with benzodiazepine receptors but has no anticonvulsant actions itself. It is suggested that Ro15-1788 is a partial agonist at the BZ2 (anticonvulsant) receptor but is an antagonist at the BZ1 (sedative, anxiolytic) receptor. CGS-8216 is an antagonist at both receptors. Ro15-1788 or related compounds may be effective anticonvulsants without the sedative side-effects usually found with the benzodiazepines.