Anticonvulsant Effects Of Phencynonate In Different Epilepsy Models

Aims The anticonvulsant effects of phencynonate were studied on different epilepsy models and its antiepileptic mechanisms were further investigated .Methods Firstly, using two acute epilepsy models (Maximal electroshock seizure, MES and Maximal metrazol test, MET) and chronic epilepsy model (PTZ-kindling model), the antiepileptic effect of phencynonate was evaluated. Secondly, the antiepileptic effects of phencynonate and its optical isomers (d-isomer and 1-isomer) were tested and compared on MES and MET. Last, we studied the antiepileptic effects of phencynonate and its optical isomers on nicotine-induced seizure model.Results Phencynonate showed very good anticonvulsant effect on MES and MET, and its anticonvulsant potency was even stronger than that of clinically used antiepileptics, barbital sodium and sodium phenytoin. Moreover, on another animal model, PTZ-kindling model, Phencynonate could not only inhibit the development of PTZ-kindling in rats, but also antagonize the PTZ-kindling seizure. As for the optical isomers, it showed that the d-isomer possessed notable anticonvulsant effect on MES and MET, with lower potency (ED₅₀) of anticonvulsant effect than that of the racemic, and that the 1-isomer was totally inactive at any tested dosage in the same tests. Concerning the affinity to N receptor, which was represented by the anticonvulsant effect of phencynonate and its optical isomers on nicotine-induced seizure model, the 1-isomer was much more potent than d-isomer and racemic.Conclusion Phencynonate, a typical cholinolytic, would be a promising anticonvulsant drug in the treatment of epilepsy, due to its significant anticonvulsant effect on acute models ( MES and MET) and chronic model (PTZ-kindling model).