Homocysteic acid: convulsant action of stereoisomers in mice

An effect of excitatory amino acid antagonists, 2-amino-7-phosphonoheptanoate (AP7), a selective N-methyl-D-aspartate (NMDA) antagonist, and gamma-D-glutamylaminomethylsulphonate (gamma-D-GAMS), a preferential kainate/quisqualate antagonist, on convulsions induced by intracerebroventricular administration of stereoisomers of homocysteic acid (HCA) was tested in mice. AP7, 0.025 mumol, blocked myoclonic seizures induced by L-HCA and D,L-HCA, and had no anticonvulsant action against D-HCA, gamma-D-GAMS, 0.5 mumol, was preferentially active against myoclonic seizures induced by D-HCA, had moderate anticonvulsant action against D,L-HCA, and no effect against seizures induced by L-HCA. These results indicate that activation of NMDA receptors contributes substantially to the convulsant action of L-HCA, while the convulsant action of D-HCA may be mediated mainly by non-NMDA related mechanisms.