Evidence that antagonism at non-NMDA receptors results in anticonvulsant action.
The effect of gamma-D-glutamylaminomethylsulphonate (gamma-D-GAMS) and 1-(p-bromobenzoyl)-piperazine-2,3-dicarboxylate (pBB-PzDA) on convulsions elicited by intracerebroventricular application of kainate (KA) and N-methyl-D-aspartate (NMDA) was studied in mice. gamma-D-GAMS, 0.0025-1.0 mumol, and pBB-PzDA, 0.001-0.2 mumol, were preferentially active against myoclonic seizures induced by kainate, but had also pronounced anticonvulsant action against NMDA. Although pBB-PzDA was a more potent anticonvulsant relative to gamma-D-GAMS, gamma-D-GAMS displayed higher kainate-selectivity. gamma-D-GAMS, 0.025 and 0.5 mumol, and pBB-PzDA, 0.1 mumol, blocked myoclonic seizures induced by kainate in the presence of 2-amino-7-phosphonoheptanoate, a selective antagonist at the NMDA receptor, with potency comparable to that for antagonism of seizures produced by kainate alone. These results indicate that antagonism at kainate receptors may contribute to anticonvulsant drug action.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology; D005973:Glutamine / Q000031:analogs & derivatives*; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate; D010879:Piperazines / Q000494:pharmacology; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*
D000927:Anticonvulsants; D005971:Glutamates; D010879:Piperazines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D005973:Glutamine; D001224:Aspartic Acid; D016202:N-Methylaspartate; C042626:gamma-glutamylaminomethylsulfonic acid; C045883:1-(4-bromobenzoyl)piperazine-2,3-dicarboxylic acid; D007608:Kainic Acid