The utility of excitatory amino acid (EAA) antagonists as analgesic agents. I. Comparison of the antinociceptive activity of various classes of EAA antagonists in mechanical, thermal and chemical nociceptive tests.
The present study was performed to assess the utility of excitatory amino acid (EAA) antagonists as analgesia agents. The antinociceptive activity of various classes of EAA antagonists was assessed in mechanical and thermal flexion reflexes tests, as well as in the formalin test. Additional testing assessed the motor dysfunction associated with antinociceptive dose levels of the agents used, by examining placing, grasping and righting reflexes, as well as occurrences of balance loss during locomotion. No antinociceptive activity was observed on any of the nociceptive measures for the non-NMDA receptor antagonists CNQX or L-AP-3. High doses of the non-competitive (PCP-site) NMDA receptor antagonist MK-801 and the allosteric-glycine receptor antagonist 7-CKA produced antinociception on both the mechanical and thermal flexion reflex measures, while a high dose of the competitive NMDA receptor antagonist CPP produced antinociception only on the thermal flexion reflex measure. Hyperalgesic effects on thermal flexion reflexes were obtained with all doses of the polyamine receptor antagonist ARCA, and with the highest dose of the allosteric-glycine receptor antagonist FICA. Formalin nociceptive behaviours were significantly reduced only by high doses of competitive (APV) and non-competitive (MK-801) NMDA receptor antagonists. The doses of EAA receptor antagonists which produced antinociceptive effects on any of the 3 nociceptive tests also produced evidence of motor dysfunction. Both competitive NMDA receptor antagonists (APV and CPP) produced disruptions of placing, grasping and righting reflexes, while 2 of the allosteric-glycine receptor antagonists (7-CKA and DCQX) significantly disrupted placing and righting reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
Coderre
Terence J
TJ
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7 Canada Centre de Recherche en Sciences Neurologiques et Département de Médecine, Université de Montréal, Montreal, Quebec H2W 1R7 Canada Department of Psychology, McGill University, Montreal, Quebec H2W 1R7 Canada.
Van Empel
Irene
I
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D005557:Formaldehyde; D006358:Hot Temperature; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D012018:Reflex / Q000187:drug effects; D013268:Stimulation, Chemical
D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; D005557:Formaldehyde