Benzodiazepine antagonist Ro 15-1788 (flumazepil) attenuates the anticonvulsant activity of diazepam in epileptic fowl.
The ability of the imidazobenzodiazepine Ro 15-1788 to displace diazepam from brain membranes in vitro and to antagonize the anticonvulsant activity of diazepam in vivo was determined in epileptic fowl. At doses of 1.0 mg/kg and higher, Ro 15-1788 significantly attenuated the anticonvulsant action of diazepam (1.0 mg/kg) in epileptic chickens. Ro 15-1788 alone exerted no anticonvulsant activity even in doses as high as 10 mg/kg. Specific binding of 10 nM [3H]diazepam to whole homogenate fractions prepared from cerebral hemispheres of epileptic fowl was inhibited by Ro 15-1788 with an IC50 of 8.5 nM and the Ki was determined to be 4.25 nM. These results suggest that Ro 15-1788 competes directly with diazepam for a binding site involved in producing anticonvulsant activity.
D000818:Animals; D002645:Chickens; D003975:Diazepam / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary*; D005260:Female; D005442:Flumazenil / Q000494:pharmacology*; D008297:Male; D011201:Poultry Diseases / Q000188:drug therapy* / Q000503:physiopathology
D005442:Flumazenil; D003975:Diazepam