甲基苯丙胺使用障碍的药物治疗:现状与未来目标》。

IF 5.1 Q1 SUBSTANCE ABUSE
Substance Abuse and Rehabilitation Pub Date : 2024-08-30 eCollection Date: 2024-01-01 DOI:10.2147/SAR.S431273
Justin R Yates
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引用次数: 0

摘要

非法使用精神兴奋剂甲基苯丙胺(METH)是一个令人担忧的重大问题,自 2010 年代中期以来,过量使用导致的死亡人数大幅增加。与其他精神兴奋剂使用障碍一样,治疗甲基苯丙胺使用障碍(MUD)所面临的一个挑战是,目前尚无可用的药物疗法来减少渴求并帮助患者戒毒。本综述的目的是讨论在测定 METH 对动物和人类的生理、认知和强化作用的实验中测试过的分子靶点。在动物实验中,有几种药物有望成为治疗 MUD 的潜在药物疗法,但却无法长期改变依赖者使用 METH 的情况(如莫达非尼、抗精神病药物、巴氯芬)。然而,这些药物以及阿托西汀和伐尼克兰等药物可能更适合作为改善 METH 拟精神作用或逆转 METH 引起的认知障碍的治疗方法。临床前研究表明,囊泡单胺转运体 2 抑制剂、代谢谷氨酸受体配体和痕量胺相关受体激动剂可有效减弱 METH 的强化作用;但要确定这些药物是否能有效治疗 MUD,还需要进行临床研究。除了在 MUD 患者中筛选这些化合物外,未来的潜在方向还包括在临床前研究中更加重视性别差异,以及利用药物遗传学方法来确定遗传变异是否可预测治疗结果。这些未来发展方向有助于为治疗 MUD 提供更好的干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacological Treatments for Methamphetamine Use Disorder: Current Status and Future Targets.

The illicit use of the psychostimulant methamphetamine (METH) is a major concern, with overdose deaths increasing substantially since the mid-2010s. One challenge to treating METH use disorder (MUD), as with other psychostimulant use disorders, is that there are no available pharmacotherapies that can reduce cravings and help individuals achieve abstinence. The purpose of the current review is to discuss the molecular targets that have been tested in assays measuring the physiological, the cognitive, and the reinforcing effects of METH in both animals and humans. Several drugs show promise as potential pharmacotherapies for MUD when tested in animals, but fail to produce long-term changes in METH use in dependent individuals (eg, modafinil, antipsychotic medications, baclofen). However, these drugs, plus medications like atomoxetine and varenicline, may be better served as treatments to ameliorate the psychotomimetic effects of METH or to reverse METH-induced cognitive deficits. Preclinical studies show that vesicular monoamine transporter 2 inhibitors, metabotropic glutamate receptor ligands, and trace amine-associated receptor agonists are efficacious in attenuating the reinforcing effects of METH; however, clinical studies are needed to determine if these drugs effectively treat MUD. In addition to screening these compounds in individuals with MUD, potential future directions include increased emphasis on sex differences in preclinical studies and utilization of pharmacogenetic approaches to determine if genetic variances are predictive of treatment outcomes. These future directions can help lead to better interventions for treating MUD.

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