EFFECTS OF NMDA RECEPTOR ANTAGONISTS ON NOCICEPTIVE RESPONSES IN-VIVO- COMPARISON OF ANTAGONISTS ACTING AT THE GLYCINE SITE WITH UNCOMPETITIVE ANTAGONISTS

We have shown that members of a new series of tricyclic pyrido-phthala zine diones, defined as glycine(B) site NMDA antagonists in vitro, are selective and systemically active NMDA antagonists in vivo. In electr ophysiological tests in alpha-chloralose anaesthetised rats, these com pounds reduced nociceptive reflex responses. In conscious rats they di splayed analgesic properties. These glycine(B) antagonists were compar ed electrophysiologically with several uncompetitive NMDA channel bloc kers. The degree of voltage dependence previously reported in vitro re lated to the effectiveness of the agents against different amplitude n ociceptive responses of spinal cord neurones in vivo.