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.
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001570:Benzodiazepinones / Q000008:administration & dosage; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy*; D005442:Flumazenil; D007696:Kindling, Neurologic / Q000187:drug effects; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A
D000927:Anticonvulsants; D001570:Benzodiazepinones; D011720:Pyrazoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005442:Flumazenil; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D003975:Diazepam