Effects of N-methyl-D-aspartate receptor antagonists on acute morphine-induced and I-methadone-induced antinociception in mice
Effects of N-methyl-D-aspartate receptor antagonists on acute morphine-induced and I-methadone-induced antinociception in mice
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DOI：
10.1016/j.jpain.2005.02.003
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发表时间：
2005-07-01
期刊：
影响因子：
4
通讯作者：
Dykstra, LA
中科院分区：
文献类型：
--
作者：
Fischer, BD;Carrigan, KA;Dykstra, LA
虽然N-甲基-D-天冬氨酸（NMDA）受体拮抗剂明显减弱阿片类药物的抗伤害性作用的耐受性的发展，但尚不清楚它们是否也改变急性阿片类药物的抗伤害性。本研究的目的是评估NMDA/阿片类药物的相互作用在C57 BL/6小鼠通过检查各种NMDA受体拮抗剂的不同选择性与μ阿片受体激动剂吗啡和L-美沙酮的组合。小鼠热板程序被用来评估吗啡的影响（0.1至10.0 mg/kg）和I-美沙酮（0.1至5.6 mg/kg）单独和用竞争性NMDA受体拮抗剂LY 235959预处理后（0.1至1.0 mg/kg）、甘氨酸位点NMDA受体拮抗剂R（+）-HA-966（10.0至56.0 mg/kg）或多胺位点和NR 2B选择性NMDA受体拮抗剂艾芬地尔（3.2至10.0 mg/kg）。吗啡和l-美沙酮产生剂量和时间依赖性增加在56摄氏度的热板lavelance。在测试的剂量下，NMDA受体拮抗剂对热板lavage没有影响。然而，当这些药物与吗啡联合使用时，对热板的反应潜伏期比单独使用吗啡显着增加。NMDA受体拮抗剂LY 235959和L-美沙酮的组合产生类似的增加热板laveletin;然而，与L-美沙酮单独使用相比，I-美沙酮与R（+）-HA-966或艾芬地尔的组合并没有增加热板laveletin。这些结果表明，一系列的NMDA受体拮抗剂增强吗啡诱导的抗伤害感受，虽然增强的l-美沙酮可能是特定的拮抗剂检查。视角：将低剂量NMDA受体拮抗剂纳入阿片类药物可能有利于通过增强阿片类药物的抗伤害效应治疗急性疼痛。(c)2005年，美国疼痛协会。
Although N-methyl-D-aspartate (NMDA) receptor antagonists clearly attenuate the development of tolerance to the antinociceptive effects of opioids, it is not clear whether they also alter acute opioid-incluced antinociception. The present study was designed to assess NMDA/opioid interactions in C57BL/6 mice by examining various NMDA receptor antagonists of different selectivity in combination with the mu opioid receptor agonists morphine and l-methadone. A mouse hot plate procedure was used to assess the effects of morphine (0.1 to 10.0 mg/kg) and I-methadone (0.1 to 5.6 mg/kg) alone and after pretreatment with the competitive NMDA receptor antagonist LY235959 (0.1 to 1.0 mg/kg), the glycine site NMDA receptor antagonist R(+)-HA-966 (10.0 to 56.0 mg/kg), or the polyamine site and NR2B selective NMDA receptor antagonist ifenprodil (3.2 to 10.0 mg/kg). Morphine and l-methadone produced dose- and time-dependent increases in 56 degrees C hot plate latencies. At the doses tested, the NMDA receptor antagonists produced no effect on hot plate latencies. However, when these drugs were combined with morphine, latency to respond to the hot plate was significantly increased from morphine alone. Combinations of the NMDA receptor antagonist LY235959 and l-methadone produced similar increases in hot plate latencies; however, combinations of I-methadone with R(+)-HA-966 or ifenprodil did not increase hot plate latencies compared with l-methadone alone. These results suggest that a range of NMDA receptor antagonists potentiate morphine-induced antinociception, although the potentiation of l-methadone might be specific to the antagonist examined. Perspective: The inclusion of low-dose NMDA receptor antagonists to opioids might be beneficial for the treatment of acute pain by enhancing the antinociceptive effects of the opioid. (c) 2005 by the American Pain Society.