PT - JOURNAL ARTICLE AU - J Chen AU - S Graham AU - F Moroni AU - R Simon TI - A study of the dose dependency of a glycine receptor antagonist in focal ischemia. DP - 1993 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 937--941 VI - 267 IP - 2 4099 - http://jpet.aspetjournals.org/content/267/2/937.short 4100 - http://jpet.aspetjournals.org/content/267/2/937.full SO - J Pharmacol Exp Ther1993 Nov 01; 267 AB - N-methyl-D-aspartate receptor antagonists are potent neuroprotectants in experimental focal cerebral ischemia, but behavioral and neuropathologic changes seen with these drugs in rodent models may limit the clinical utility of these compounds. Glycine's modulation of N-methyl-D-aspartate channel function offers another pharmacologic approach to excitotoxicity in ischemia. The potent glycine antagonist 7 Chlorothiokynurenic acid (7-Cl-Thio-Kyna) was studied in a permanent middle cerebral artery occlusion stroke model in the rat. The compound was effective, in a dose-dependent manner, in attenuating infarct size when administered before or after permanent middle cerebral artery occlusion. Its activity was mainly due to glycine antagonism inasmuch as 5 Chlorothiokynurenic acid, a compound having other pharmacological activities in common with 7-CI-Thio-Kyna (for instance the radical scavenger action), was inactive in this model. 7-Cl-Thio-Kyna did not produce cytological changes similar to MK 801.