Production of convulsions in mice by the combination of methionine and homocysteine

Abstract

Behavioral effects of methionine have been attributed to either increased availability of methyl groups for the production of methylated amines or accumulation of convulsive metabolites. If the second hypothesis is correct, methionine would be expected to have convulsive properties either by itself or in combination with subconvulsive dosages of other known convulsants. Methionine alone did not induce convulsions when administered by various routes in dosages of 250--13,000 mg/kg, although larger doses of methionine (500--4,000 mg/kg) decreased behavioral activity. However, methionine pretreatment (125--1,000 mg/kg) markedly enhanced convulsions in animals challenaed with subconvulsine dosages of homocysteine. Pentylenetetrazol was less effective than homocysteine in promoting convulsions in methionine-pretreated animals. Although the convulsive effects of methionine were not shared by other natural amino acids (glutamate, asparate, cysteine, tryptophan, and others), ethionine enhanced homocysteine-induced convulsions almost as effectively as did methionine. Methionine thus promotes convulsions under certain conditions, plerhaps due to an accumulation of homocysteine or of other metabolites with convulsive properties.U