From the, Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Alcohol Clin Exp Res. 2020 Oct;44(10):1965-1976. doi: 10.1111/acer.14445. Epub 2020 Sep 20.
Alcohol use disorder (AUD) is 1 of the most prevalent of all substance use disorders and contributes significantly to global disease burden. Despite its prevalence, <10% of individuals with AUD receive treatment. A significant barrier to receiving treatment is a lack of effective pharmacotherapies. While 3 medications have been approved by the FDA for AUD (disulfiram, acamprosate, naltrexone), their efficacy remains low. Furthermore, a number of undesirable side effects associated with these drugs further reduce patient compliance. Thus, research into new effective pharmacotherapies for AUD is warranted. Due to their involvement in regulating synaptic neurotransmitter levels, solute carrier (SLC) transporters could be targeted for developing effective treatment strategies for AUD. Indeed, a number of studies have shown beneficial reductions in alcohol consumption through the use of drugs that target transporters of dopamine, serotonin, glutamate, glycine, and GABA. The purpose of this narrative review is to summarize preclinical and clinical studies from the last 2 decades targeting SLC neurotransmitter transporters for the treatment of AUD. Limitations, as well as future directions for expanding this field, are also discussed.
酒精使用障碍(AUD)是所有物质使用障碍中最普遍的一种,对全球疾病负担有重大影响。尽管 AUD 很普遍,但<10%的患者接受治疗。接受治疗的一个主要障碍是缺乏有效的药物治疗。尽管有 3 种药物已被 FDA 批准用于 AUD(双硫仑、安非他酮、纳曲酮),但其疗效仍然较低。此外,这些药物的一些不良副作用进一步降低了患者的依从性。因此,有必要研究用于 AUD 的新的有效药物治疗方法。由于它们参与调节突触神经递质水平,溶质载体(SLC)转运蛋白可能成为开发 AUD 有效治疗策略的目标。事实上,许多研究表明,通过使用针对多巴胺、血清素、谷氨酸、甘氨酸和 GABA 转运蛋白的药物,可以有益地减少饮酒量。本综述的目的是总结过去 20 年针对 SLC 神经递质转运蛋白治疗 AUD 的临床前和临床研究。还讨论了该领域的局限性以及未来的扩展方向。