Antinociceptive actions of different classes of excitatory amino acid receptor antagonists in mice.
Intrathecal (i.t.) injection of the competitive and selective N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-5-phosphonopentanoic acid (AP5), D-2-amino-7-phosphonoheptanoic acid (AP7), beta-D-aspartylaminomethyl phosphonic acid (Asp-AMP), 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and gamma-D-glutamylaminomethyl phosphonic acid (Glu-AMP) produced dose-dependent and reversible analgesic effects in the mouse hot-plate and formalin tests of nociception. They were slightly more potent in the formalin test but had no or negligible effects in the tail-flick test. The non-selective or non-NMDA receptor antagonists 6-cyano-7-nitro-quinoxalinedione (CNQX), 6,7-dinitro-quinoxalinedione (DNQX), gamma-D-glutamylglycine (gamma DGG), gamma-glutamylaminomethyl sulphonic acid (GAMS), kynurenic acid, cis-2,3-piperidine dicarboxylic acid (cis-PDA; partial agonist) and p-bromobenzoyl piperazine dicarboxylic acid (pBB-PzDA) had the same efficacy in the mouse hot-plate, tail-flick and formalin tests (gamma DGG and pBB-PzDA were not tested in the formalin test). This heterogeneous group of antagonists was somewhat more potent in the tail-flick test and slightly less potent in the formalin test than in the hot-plate test. Of the two glycine site antagonists tested, 7-chlorokynurenic acid (7-Cl-Kyn) and (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), the effect of the latter was compatible with selective action at the NMDA receptor complex while the action of the former was comparable to those of non-selective excitatory amino acid (EAA) receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Näsström
J
J
Astra Pain Control, Preclinical Research, Södertälje, Sweden.
Karlsson
U
U
Post
C
C
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007278:Injections, Spinal; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012694:Serine / Q000494:pharmacology
D000700:Analgesics; D010879:Piperazines; D011810:Quinoxalines; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; C056723:FG 9041; D007649:Ketamine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid