PT  - JOURNAL ARTICLE
AU  - Koek, W
AU  - Colpaert, F C
TI  - Selective blockade of N-methyl-D-aspartate (NMDA)-induced convulsions by NMDA antagonists and putative glycine antagonists: relationship with phencyclidine-like behavioral effects.
DP  - 1990 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 349--357
VI  - 252
IP  - 1
4099  - http://jpet.aspetjournals.org/content/252/1/349.short
4100  - http://jpet.aspetjournals.org/content/252/1/349.full
SO  - J Pharmacol Exp Ther1990 Jan 01; 252
AB  - Antagonism of N-methyl-D-aspartate (NMDA)-induced convulsions by a variety of drugs was compared with their ability to produce phencyclidine (PCP)-like behavioral effects (locomotion and falling) in mice. Convulsions produced by i.c.v. administration of NMDA were antagonized, at doses that did not block kainate- and quisqualate-induced convulsions, by competitive NMDA antagonists (e.g., CPP and CGS 19755), noncompetitive antagonists (e.g., PCP and MK-801) and also by some putative glycine antagonists (7-chlorokynurenic acid and HA-966). Only the competitive and the noncompetitive NMDA antagonists produced locomotion and falling, and their potencies to do so correlated (r = 0.92) with their relative potencies to antagonize NMDA-induced convulsions. However, the PCP-like behavioral effects produced by the competitive antagonists were of a lesser magnitude than those of the noncompetitive antagonists, and occurred at doses higher than those needed to block NMDA-induced convulsions. The putative glycine antagonists 7-chlorokynurenic acid and HA-966 selectively blocked NMDA-induced convulsions, without producing PCP-like behavioral effects. The extent to which compounds produce PCP-like behavioral effects might depend in part on the specific component of the NMDA receptor complex with which they interact: i.e., the NMDA receptor, the NMDA receptor-associated ion channel or the glycine-sensitive modulatory site.