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 pyridophthalazine diones, defined as glycineB site NMDA antagonists in vitro, are selective and systemically active NMDA antagonists in vivo. In electrophysiological tests in alpha-chloralose anaesthetised rats, these compounds reduced nociceptive reflex responses. In conscious rats they displayed analgesic properties. These glycineB antagonists were compared electrophysiologically with several uncompetitive NMDA channel blockers. The degree of voltage dependence previously reported in vitro related to the effectiveness of the agents against different amplitude nociceptive responses of spinal cord neurones in vivo.
McClean
M
M
University of Bristol, Department of Physiology, School of Medical Sciences, United Kingdom.
Chizh
B A
BA
Headley
P M
PM
D000818:Animals; D003655:Decerebrate State; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology*; D005998:Glycine / Q000378:metabolism*; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010793:Phthalazines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D010793:Phthalazines; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine