Laboratory on the Biology of Addictive Diseases, The Rockefeller University, New York, New York.
Hum Psychopharmacol. 2020 Mar;35(2):e2726. doi: 10.1002/hup.2726. Epub 2020 Feb 12.
Naltrexone and nalmefene are approved for the treatment of alcohol use disorders, in different countries. Naltrexone is also approved for the treatment for opioid use disorders, most recently in a depot formulation. These compounds target primarily μ(mu)- and κ(kappa)-opioid receptor systems, which are involved in the downstream neurobiological effects of alcohol and in the modulation of neuroendocrine stress systems. The study objective was to compare the neuroendocrine effects of naltrexone and nalmefene on adrenocorticotropic hormone (ACTH), cortisol, and prolactin, in normal volunteers.
Adult normal volunteers (n = 11 male and n = 9 female) were studied in a stress-minimized inpatient setting on three consecutive days, after intravenous saline, naltrexone HCl (10 mg), or nalmefene HCl (10 mg), in fixed order. ACTH, cortisol, and prolactin were analyzed pre-injection and up to 180 min post-injection.
Naltrexone and nalmefene caused elevations in ACTH and cortisol compared with saline. Nalmefene had a greater effect on ACTH and cortisol, compared with naltrexone. Both compounds also caused elevations in prolactin in males (females were not examined, due to the influence of menstrual cycle on prolactin).
This study suggests that both nalmefene and naltrexone have effects potentially due to κ-partial agonism in humans, as well as antagonist effects at μ-receptors.
纳曲酮和纳美芬已在不同国家获得批准，用于治疗酒精使用障碍。纳曲酮最近也被批准用于治疗阿片类药物使用障碍，以长效制剂的形式。这些化合物主要针对μ（mu）-和κ（kappa）-阿片受体系统，该系统参与酒精的下游神经生物学效应和神经内分泌应激系统的调节。本研究旨在比较纳曲酮和纳美芬对正常志愿者促肾上腺皮质激素（ACTH）、皮质醇和催乳素的神经内分泌效应。
11 名男性和 9 名女性成年正常志愿者在应激最小化的住院环境中连续 3 天进行研究，静脉注射生理盐水、纳曲酮 HCl（10mg）或纳美芬 HCl（10mg），固定顺序。在注射前和注射后最多 180 分钟分析 ACTH、皮质醇和催乳素。
与生理盐水相比，纳曲酮和纳美芬使 ACTH 和皮质醇升高。与纳曲酮相比，纳美芬对 ACTH 和皮质醇的影响更大。两种化合物还导致男性催乳素升高（女性未进行检查，因为催乳素受月经周期的影响）。
本研究表明，纳美芬和纳曲酮都具有潜在的 κ-部分激动作用，以及 μ-受体拮抗剂作用，这可能是其在人类中的作用机制。
