Egyptian Journal of Basic and Clinical Pharmacology

Egyptian Journal of Basic and Clinical Pharmacology
Vol. 5 (2015), Issue 1, pp. 11-18
doi:10.11131/2015/101356

Effect of Verapamil, Cinnarizine and Memantine on Maximal Electroshock, Picrotoxin, and Pilocarpine-Induced Seizure Models in Albino Mice

Background: Epilepsy is a common neurological disorder with a serious socioeconomic impact. NMDA and L as well as T- type calcium channels share in epileptic depolarization of neurons. Calcium channel blockers and NMDA receptor antagonists could protect against epilepsy. Verapamil and cinnarizine block L and T-type calcium channels respectively, while memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist. Maximal electroshock seizure (MES) and picrotoxin are models of generalized tonic-clonic and complex partial seizures. MES identifies drugs acting on Na+ channels while picrotoxin is GABAA receptor antagonist. Lithium-pilocarpine model induces status epilepticus-like state acting through muscarinic and NMDA receptors. The aim of the present work is to assess effects of verapamil, cinnarizine and memantine on Maximal electroshock, picrotoxin and pilocarpine-induced seizure models in albino mice. Methods: Maximal electroshock, picrotoxin and lithium-pilocarpine-induced seizure models were utilized to test the potential antiepileptic effect of verapamil, cinnarizine and memantine. Results: Verapamil decreased the mean latency period in pilocarpine model. Cinnarizine increased the mean latency period in picrotoxin and pilocarpine models as well as protected from convulsions partially in picrotoxin model and completely in pilocarpine model. Memantine increased the electroconvulsive threshold and the mean latency period in maximal electroshock and pilocarpine models respectively while, decreased the mean latency period in picrotoxin model. Conclusion: Verapamil potentiated seizure occurrence in pilocarpine model. Cinnarizine protected from convulsions, partially in picrotoxin and completely in pilocarpine models. Memantine had anticonvulsant effect in maximal electroshock and pilocarpine models but, potentiated the occurrence of seizures in picrotoxin model.