Anticonvulsant action of stereoisomers of gamma-glutamylaminomethylsulphonic acid in mice.
The effects of stereoisomers of gamma-glutamylaminomethylsulphonic acid (GAMS) on convulsions produced by intracerebroventricular injections of excitatory amino acids were studied in mice. gamma-D-GAMS preferentially blocked myoclonic seizures induced by kainate and had less pronounced anticonvulsant effect against quisqualate, N-methyl-D-aspartate, quinolinate, D-homocysteine sulphinate and L-glutamate. gamma-L-GAMS displayed only a relatively weak protective effect against kainate- and, to some extent, quisqualate-induced seizures, with little or no effect on the convulsant properties of the other excitatory amino acids. These results indicate that the D configuration of the gamma-carbon atom of excitatory amino acid antagonists is preferred not only for NMDA receptor antagonism but for antagonism at non-NMDA receptors as well.
Turski
L
L
Meldrum
B S
BS
Jones
A W
AW
Watkins
J C
JC
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D005971:Glutamates / Q000494:pharmacology*; D005973:Glutamine / Q000031:analogs & derivatives*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D005973:Glutamine; D001224:Aspartic Acid; D016202:N-Methylaspartate; C042626:gamma-glutamylaminomethylsulfonic acid; D007608:Kainic Acid