Interaction of abecarnil, bretazenil, and RO 19-8022 with diazepam-sensitive and -insensitive benzodiazepine sites in the rat cerebellum and cerebral cortex.
Abecarnil, bretazenil, and Ro 19-8022 inhibited the binding of [3H]Ro 15-4513 to diazepamsensitive and -insensitive sites in the rat cerebellum and cerebral cortex, but all three had a much higher affinity for the diazepam-sensitive sites in both tissues. The GABA-shift for bretazenil and Ro 19-8022 was low ( < 2) for all sites studied, consistent with their partial agonistic profile. The GABA-shift for abecarnil was appreciably higher for diazepam-sensitive binding in the cerebellum than in the cerebral cortex (1.97 vs 1.18). Furthermore, the GABA-shift for abecarnil was markedly different for the diazepam-sensitive and -insensitive sites in the cerebellum (1.97 vs 0.71). All three compounds inhibited [3H]Ro 15-4513 binding to the diazepam-sensitive sites with a slope factor > 1, suggestive of positive cooperativity in their binding to GABAA receptors. Abecarnil only partially inhibited diazepam-insensitive binding of [3H]Ro 15-4513 in the cerebellum, indicating that this site can be differentiated into abecarnil-sensitive and -insensitive components.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology*; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D002243:Carbolines; D011759:Pyrrolidines; D011807:Quinolizines; D011963:Receptors, GABA-A; C076809:Ro 19-8022; C062769:abecarnil; C054626:bretazenil; D003975:Diazepam