Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain.
Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain.
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DOI：
10.1016/j.neuropharm.2009.04.010
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发表时间：
2009-08
影响因子：
4.7
通讯作者：
Pan, Hui-Lin
中科院分区：
文献类型：
--
作者：
Chen, Shao-Rui;Samoriski, Gary;Pan, Hui-Lin
糖尿病神经性疼痛仍然是一个未解决的临床问题，传统的镇痛药缓解效果不佳。N-甲基-D-天冬氨酸（NMDA）受体在神经病理性疼痛的中枢敏化中起重要作用。虽然NMDA拮抗剂在减少神经性疼痛方面非常有效，但这些药物在治疗剂量下会引起严重的副作用，这限制了它们的临床应用。奈拉美生和美金刚是非竞争性NMDA拮抗剂，在治疗剂量下副作用极小。在这里，我们确定了长期给予奈拉美生的抗伤害性作用，并将其与美金刚和加巴喷丁在糖尿病神经病理性疼痛大鼠模型中的作用进行了比较。机械性痛觉过敏与伤害性压力刺激进行了测量，触觉异常性疼痛进行了评估与冯弗雷细丝糖尿病大鼠链脲佐菌素。与溶媒给药大鼠相比，通过渗透性微型泵给予奈拉美生（12.3、24.6和49.2 mg/kg/天）2周对机械性痛觉过敏和异常性疼痛产生了剂量依赖性和持续效应。美金刚（20 mg/kg/天）或加巴喷丁（50 mg/kg/天）给药2周也对机械性痛觉过敏和异常性疼痛产生显著和持续的抗伤害性作用。中等剂量和高剂量奈拉美生产生的抗伤害效应的幅度与加巴喷丁和美金刚相当。奈拉美生在12.3、24.6和49.2 mg/kg/天剂量下达到的血浆水平分别为0.26 ± 0.04、0.50 ± 0.05和1.21 ± 0.16 μM。这些数据表明，治疗相关剂量的奈拉美生可减轻糖尿病神经性疼痛。我们的研究提供了有价值的信息，慢性给药奈拉美生和美金刚治疗糖尿病神经病变疼痛的治疗潜力。
Diabetic neuropathic pain remains an unmet clinical problem and is poorly relieved by conventional analgesics. N-methyl-D-aspartate (NMDA) receptors play an important role in central sensitization in neuropathic pain. Although NMDA antagonists are highly effective in reducing neuropathic pain, these agents cause severe side effects at therapeutic doses, which limit their clinical uses. Neramexane and memantine are uncompetitive NMDA antagonists with minimal side effects at therapeutic doses. Here we determined the antinociceptive effect of chronic administration of neramexane and compared its effect with that of memantine and gabapentin in a rat model of diabetic neuropathic pain. Mechanical hyperalgesia was measured with a noxious pressure stimulus, and tactile allodynia was assessed with von Frey filaments in diabetic rats induced by streptozotocin. Compared with vehicle-treated rats, treatment with neramexane (12.3, 24.6, and 49.2 mg/kg/day) for 2 weeks via an osmotic minipump produced dose-dependent and sustained effects on mechanical hyperalgesia and allodynia. Administration of memantine (20 mg/kg/day) or gabapentin (50 mg/kg/day) for 2 weeks also produced significant and persistent antinociceptive effects on mechanical hyperalgesia and allodynia. The magnitude of the antinociceptive effect produced by the intermediate and high doses of neramexane was comparable to that of gabapentin and memantine. The plasma level achieved by neramexane at 12.3, 24.6, and 49.2 mg/kg/day was 0.26 ± 0.04, 0.50 ± 0.05, and 1.21 ± 0.16 μM, respectively. These data suggest that neramexane at therapeutically relevant doses attenuates diabetic neuropathic pain. Our study provides valuable information about the therapeutic potential of chronic administration of neramexane and memantine for painful diabetic neuropathy.
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影响因子：
8.8
作者：
Chen, SR;Khan, GM;Pan, HL
通讯作者：
Pan, HL
DOI：
10.1007/bf02253435
发表时间：
1994-01-01
期刊：
JOURNAL OF NEURAL TRANSMISSION-PARKINSONS DISEASE AND DEMENTIA SECTION
影响因子：
--
作者：
DANYSZ, W;GOSSEL, M;QUACK, G
通讯作者：
QUACK, G
影响因子：
3.3
作者：
Khan, GM;Chen, SR;Pan, HL
通讯作者：
Pan, HL
影响因子：
3.1
作者：
Correll, GE;Maleki, J;Harbut, RE
通讯作者：
Harbut, RE
影响因子：
2.5
作者：
Chen, SR;Pan, HL
通讯作者：
Pan, HL