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• W1963519570 abstract "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. The non-competitive NMDA antagonist MK-801 also produced evidence of balance loss and falling. The data indicate that the doses of EAA antagonists which produce significant antinociceptive effects also produce evidence of motor dysfunction. This suggests that EAA receptor antagonists may have a limited therapeutic range and, therefore, may not be particularly useful as analgesic agents for the treatment of clinical pain. Studies in the following article suggest that this problem may be overcome by using low-dose combinations of agents acting at various components of the NMDA receptor complex." @default.
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• W1963519570 title "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" @default.
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• W1963519570 doi "https://doi.org/10.1016/0304-3959(94)90020-5" @default.
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