Selective blockade of N-methyl-D-aspartate (NMDA)-induced convulsions by NMDA antagonists and putative glycine antagonists: Relationship with phencyclidine-like behavioral effects

W. Koek, F. C. Colpaert

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)349-357
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume252
Issue number1
StatePublished - Jan 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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