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.
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.
X M
XM
Gao
D M
DM
Chuang
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003594:Cytoplasmic Granules / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D019832:N-Methylscopolamine; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D010042:Ouabain / Q000494:pharmacology; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012602:Scopolamine Derivatives / Q000378:metabolism / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D010276:Parasympatholytics; D012602:Scopolamine Derivatives; D002220:Carbamazepine; D010042:Ouabain; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D000254:Sodium-Potassium-Exchanging ATPase; D019832:N-Methylscopolamine