谷氨酸系统在阿片类药物耐受和依赖中的作用的临床前证据

Charles E. Inturrisi
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引用次数: 59

摘要

阿片类药物耐受性和身体依赖是慢性阿片类药物使用或滥用的不良后果。来自啮齿类动物的证据表明,在NMDA受体复合物的竞争性、非竞争性或甘氨酸结合位点具有谷氨酸能拮抗剂活性的药物或某些形式的一氧化氮合酶(NOS)抑制剂可以减弱吗啡耐受性的发展,在某些情况下逆转已建立的耐受性或依赖性。其中一些药物在不影响吗啡镇痛作用的情况下调节耐受性和依赖性,这表明它们阻止了由NMDA/NO级联介导的适应性变化相关的神经元可塑性。具有良好临床前安全裕度的药物为新药的临床评价提供了线索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preclinical Evidence for a Role of Glutamatergic Systems in Opioid Tolerance and Dependence

Opioid tolerance and physical dependence are undesirable consequences of chronic opioid use or misuse. Evidence from rodents, using a variety of modes of drug coadministration, reveals that drugs with glutamatergic antagonist activity at the competitive, noncompetitive, or glycine binding sites of the NMDA receptor complex or inhibitors of certain forms of nitric oxide synthase (NOS) can attenuate the development of morphine tolerance and in some cases reverse established tolerance or dependence. Some of these drugs modulate tolerance and dependence without affecting morphine's analgesic effects, suggesting that they prevent neuronal plasticity associated with adaptive changes mediated by the NMDA/NO cascade. Drugs that have a favorable preclinical safety margin are providing leads for new drugs for clinical evaluation.

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