Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors
Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors
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DOI：
10.1126/science.279.5347.77
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发表时间：
1998-01-02
期刊：
影响因子：
56.9
通讯作者：
Arneric, SP
中科院分区：
文献类型：
--
作者：
Bannon, AW;Decker, MW;Arneric, SP
开发用于治疗严重疼痛的镇痛剂需要鉴定没有阿片受体倾向的化合物。开发了一种称为ABT-594的有效（抑制常数= 37皮摩尔）神经元烟碱乙酰胆碱受体（nAChR）配体，其在急性热、持续性化学和神经病理性疼痛状态的一系列不同动物模型中具有与吗啡相同的抗伤害感受特性。这些作用被nAChR拮抗剂美加明阻断。与吗啡相反，用ABT-594重复治疗似乎不会引起阿片样戒断或身体依赖。因此，ABT-594可能是一种没有阿片类镇痛相关问题的镇痛剂。
Development of analgesic agents for the treatment of severe pain requires the identification of compounds that are devoid of opioid receptor liabilities. A potent (inhibition constant = 37 picomolar) neuronal nicotinic acetylcholine receptor (nAChR) ligand called ABT-594 was developed that has antinociceptive properties equal in efficacy to those of morphine across a series of diverse animal models of acute thermal, persistent chemical, and neuropathic pain states. These effects were blocked by the nAChR antagonist mecamylamine. In contrast to morphine, repeated treatment with ABT-594 did not appear to elicit opioid-like withdrawal or physical dependence. Thus, ABT-594 may be an analgesic that lacks the problems associated with opioid analgesia.