Prolongation of morphine analgesia by competitive NMDA receptor antagonist D-CPPene (SDZ EAA 494) in rats
Prolongation of morphine analgesia by competitive NMDA receptor antagonist D-CPPene (SDZ EAA 494) in rats
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DOI：
10.1016/s0014-2999(98)00324-0
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发表时间：
1998-06-26
影响因子：
5
通讯作者：
Zvartau, E
中科院分区：
文献类型：
--
作者：
Bespalov, A;Kudryashova, M;Zvartau, E
NMDA受体拮抗剂未来可能的临床应用是控制阿片类镇痛耐受的发展。因此，NMDA受体拮抗剂改变阿片类药物急性镇痛作用的能力变得越来越重要。本研究旨在评估吗啡（5- 20mg /kg）和竞争性NMDA受体拮抗剂D-CPPene (SDZ EAA 494; 3-（2-羧基哌嗪-4-基）-1-丙烯-1-膦酸；0.3 ~ 5.6 mg/kg)的大鼠甩尾和捏尾试验。结果发现，D-CPPene显著增加吗啡镇痛持续时间，但几乎没有证据表明吗啡给药后不久吗啡镇痛会增强。这种影响只能部分归因于d - cppene诱导的“习得性高反应性”发展的中断（即，获得较低的潜伏期以逃避反复暴露于有害刺激）。此外，与D-CPPene同时治疗对吗啡血药浓度无影响。(C) 1998 Elsevier Science B.V.版权所有
A possible future clinical application of NMDA receptor antagonists is the control of the development of opiate analgesic tolerance. Therefore, the ability of NMDA receptor antagonists to modify the acute analgesic effects of opiates becomes increasingly important. The present study sought to evaluate the analgesic potency of combined administration of morphine (5-20 mg/kg) and a competitive NMDA receptor antagonist D-CPPene (SDZ EAA 494; 3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid; 0.3-5.6 mg/kg) in the tail-flick and tail-pinch tests with rats. It was found that D-CPPene significantly increased the duration of morphine analgesia, but there was hardly any evidence for potentiation of morphine analgesia shortly after morphine administration. This effect could only in part be attributed to the D-CPPene-induced disruption of the development of 'learned hyperresponsiveness' (i.e., acquisition of decreased latencies to escape from repeated exposures to noxious stimulation). In addition, the plasma concentration of morphine was not affected by concurrent treatment with D-CPPene. (C) 1998 Elsevier Science B.V. All rights reserved.