Carbamazepine inhibits distinct chemoconvulsant-induced seizure-like activity in Dugesia tigrina

Abstract

Planaria, non-parasitic flatworms, were recently shown to be a simple yet sensitive model for investigating the pharmacology of convulsants and anticonvulsants. The present findings show that three distinct chemoconvulsants, (−)-nicotine, picrotoxin, and N-methyl-d-aspartate (NMDA), induce dose-dependent seizure-like paroxysms in the planarian Dugesia tigrina. Carbamazepine and oxcarbazepine, iminodibenzyl derivatives, exhibit anticonvulsive effects mediated mainly through the inactivation of voltage-gated sodium channels. Apart from these primary molecular targets, both carbamazepine and oxcarbazepine are known to activate γ-aminobutyric acid type A (GABAA) receptors and inhibit NMDA activated glutamate receptors and neuronal nicotinic acetylcholine receptors (nAChRs). The present study shows that in D. tigrina both carbamazepine and oxcarbazepine inhibit chemoconvulsant-induced seizure behaviors in a dose-dependent manner. Carbamazepine (100μM) decreased by ~65% the cumulative mean planarian seizure-like activity (pSLA) observed in the presence of (−)-nicotine (10μM), picrotoxin (5mM), or NMDA (3mM), whereas oxcarbazepine (1μM) decreased by 45% the cumulative mean pSLA induced by (−)-nicotine (10μM). The results demonstrate, for the first time, the anti-seizure pharmacology of carbamazepine and oxcarbazepine in an invertebrate seizure model.