Herman B H, Vocci F, Bridge P
Medications Development Division, National Institute on Drug Abuse, National Institutes of Health, Rockville, MD 20857, USA.
Neuropsychopharmacology. 1995 Dec;13(4):269-93. doi: 10.1016/0893-133X(95)00140-9.
This article is an exploration of the National Institute on Drug Abuse (NIDA) Technical Review on the role of glutamatergic systems in the development of opiate addiction. The effects of "glutamate antagonist" medications on opioid tolerance and withdrawal are examined. In rodents, mu opioid tolerance can be inhibited by noncompetitive N-methyl D-aspartate (NMDA) receptor antagonists [MK801, dextromethorphan (DM), ketamine, phencyclidine (PCP)], competitive NMDA receptor antagonists (LY274614, NPC17742, LY235959), partial glycine agonists (ACPC), glycine antagonists (ACEA-1328), and nitric oxide synthase (NOS) inhibitors [L-NNA, L-NMMA, methylene blue (MB)]. Similarly, some of the symptoms of opioid withdrawal observed in opioid-dependent rodents also can be inhibited by noncompetitive NMDA receptor antagonists (MK801, DM, ketamine), competitive NMDA receptor antagonists (LY274614), glycine antagonists (felbamate), and NOS inhibitors (L-NNA, L-NMMA, L-NAME, L-NIO, 7-NI, MB). There are some serious toxicological effects associated with the administration of some of the noncompetitive NMDA receptor antagonists in rodent but not in squirrel monkey brain, and some medications induce PCP-like behavioral effects. The medications with the most immediate clinical appeal are those that could be coadministered with methadone to decrease mu opioid tolerance and dependence; they include DM, MB, 7-NI, ACPC, and ACEA-1328.
本文探讨了美国国立药物滥用研究所（NIDA）关于谷氨酸能系统在阿片类药物成瘾发展中作用的技术审查。研究了“谷氨酸拮抗剂”药物对阿片类药物耐受性和戒断反应的影响。在啮齿动物中，μ阿片类药物耐受性可被非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂[MK801、右美沙芬（DM）、氯胺酮、苯环己哌啶（PCP）]、竞争性NMDA受体拮抗剂（LY274614、NPC17742、LY235959）、部分甘氨酸激动剂（ACPC）、甘氨酸拮抗剂（ACEA-1328）以及一氧化氮合酶（NOS）抑制剂[L-NNA、L-NMMA、亚甲蓝（MB）]所抑制。同样，在阿片类药物依赖的啮齿动物中观察到的一些阿片类药物戒断症状也可被非竞争性NMDA受体拮抗剂（MK801、DM、氯胺酮）、竞争性NMDA受体拮抗剂（LY274614）、甘氨酸拮抗剂（非氨酯）以及NOS抑制剂（L-NNA、L-NMMA、L-NAME、L-NIO、7-NI、MB）所抑制。在啮齿动物而非松鼠猴大脑中，给予某些非竞争性NMDA受体拮抗剂会产生一些严重的毒理学效应，并且一些药物会诱发类似PCP的行为效应。最具直接临床应用价值的药物是那些可与美沙酮联合使用以降低μ阿片类药物耐受性和依赖性的药物；它们包括DM、MB、7-NI、ACPC和ACEA-1328。
