Carbamazepine-induced neurotoxicity and its prevention by NMDA in cultured cerebellar granule cells.

Long-term neurotoxicity of carbamazepine was studied in cultured cerebellar granule cells. Treatment of cells with carbamazepine for 3 days induced a dose-dependent neurotoxicity detected by a loss of [3H]ouabain binding to Na+,K(+)-ATPase, and [3H]N-methyl scopolamine binding to muscarinic cholinergic receptors as well as by direct morphologic examination. NMDA protected against carbamazepine-induced toxicity and this protection was blocked by 2-amino-5-phosphono-valerate (APV). The neurotoxicity induced by carbamazepine may be involved in the teratogenic and adverse effects of overdose associated with the treatment of manic-depressive illness and seizures.