title: 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 (GABA(A)) 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 (100 μM) decreased by ~65% the cumulative mean planarian seizure-like activity (pSLA) observed in the presence of (-)-nicotine (10 μM), picrotoxin (5mM), or NMDA (3mM), whereas oxcarbazepine (1 μM) 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.
authors.affiliation: Department of Chemistry, Saint Cloud State University, Saint Cloud, MN 56301-4498, USA. lramakrishnan@stcloudstate.edu
authors.forename: Latha
authors.initials: L
authors.lastname: Ramakrishnan
authors.forename: Cassie
authors.initials: C
authors.lastname: Desaer
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D000078330:Oxcarbazepine; D010852:Picrotoxin / Q000494:pharmacology; D010932:Planarians / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D016202:N-Methylaspartate; D009538:Nicotine; D018722:Nicotinic Agonists; D000078330:Oxcarbazepine; D010852:Picrotoxin