Modulatory effect of alpha 2 adrenoceptor agonists on Ro 5-4864-induced convulsions in rats and mice

The protective effect of various alpha 2 adrenoceptor agonists such as clonidine, guanfacine, B-HT 920 and ICI 106270 was investigated against Ro 5-4864-induced convulsions in mice and rats. Clonidine and ICI 106270 exhibited a profound anticonvulsant effect while equivalent doses of guanfacine and B-HT 920 were less effective. The anticonvulsant effect of clonidine and ICI 106270 was reversed by pretreatment with yohimbine or idazoxan, indicating the involvement of alpha 2 adrenoceptors in their protective effect. Diazepam, clonazepam, CL 218, 872 and pentobarbitone exhibited a different profile of protective action, as these agents protected the animals from apparent mortality as compared to clonidine and ICI 106270 which prolonged the latencies of jerk and convulsion. Modulatory effects of alpha 2 adrenoceptors in central GABA function and multiple sites for Ro 5-4864-induced seizures are explained.