title: Antagonism of N-methyl-D,L-aspartic acid-induced convulsions by antiepileptic drugs and other agents.
abstract: The effects of common antiepileptics, GABAmimetic drugs, excitatory amino acid antagonists as well as of clonidine, corynanthine, chlorpromazine and atropine were studied against clonic convulsions induced in mice by N-methyl-D,L-aspartic acid (NMDLA) after subcutaneous (340 mg/kg; ED97) and intravenous (105 mg/kg; ED97) administration. Among the antiepileptics studied, valproate (ED50: 340 mg/kg after subcutaneous injection of NMDLA) and diazepam (ED50: 0.78 mg/kg after intravenous and 14 mg/kg after subcutaneous injection of NMDLA) antagonized NMDLA-induced convulsions, whereas phenobarbital (up to 80 mg/kg), diphenylhydantoin (up to 50 mg/kg) and ethosuximide (500 mg/kg) were totally ineffective. Moreover, 2-amino-5-phosphonopentanoic acid and 2-amino-7-phosphonoheptanoic acid (but not glutamic acid diethyl ester), aminooxyacetic acid, cetyl GABA and clonidine protected strongly against the convulsant whereas progabide was only weakly active. THIP showed a higher activity against intravenous than against subcutaneous NMDLA. Baclofen and atropine even increased mortality and the remaining agents exerted no significant protective action. The data suggest that NMDLA-induced convulsions can be blocked effectively by direct antagonism of NMDLA-produced excitation, enhancement of GABA-mediated inhibition, and activation of central alpha 2-adrenoceptors. The possible efficacy of valproate in cases of epilepsy with a distinct rise in plasma excitatory amino acid levels should be carefully considered.
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D016202:N-Methylaspartate; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants; D001224:Aspartic Acid; D016202:N-Methylaspartate