Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506-9500, USA.
Curr Pharm Des. 2012;18(7):902-19. doi: 10.2174/138161212799436601.
Drug abuse is currently a large economic and societal burden in countries around the globe. Many drugs of abuse currently lack adequate therapies aimed at treating both the addiction and negative complications often associated with their use. Sigma-1 receptors were discovered over 30 years ago and have recently become targets for the development of pharmacotherapies aimed at treating substance abuse and addiction. In vivo preclinical studies have revealed that sigma receptor ligands are able to ameliorate select behavioral effects of many drugs of abuse including cocaine, methamphetamine, ethanol and nicotine. In addition, recent studies have begun to elucidate the mechanisms by which sigma-1 receptors modulate the effects of these drugs on neurotransmission, gene regulation and neuroplasticity. Overall, these recent findings suggest that compounds targeting sigma-1 receptors may represent a potential new class of therapeutics aimed at treating drug abuse. Future studies involving clinical populations will be critical for validating the therapeutic potential of sigma-1 receptor ligands for the treatment of substance abuse.
药物滥用是当前全球各国面临的一个重大的经济和社会负担。目前,许多滥用药物缺乏针对成瘾和与其使用相关的负面并发症的有效治疗方法。西格玛-1 受体在 30 多年前被发现,最近已成为开发旨在治疗药物滥用和成瘾的药物治疗方法的靶点。体内临床前研究表明,西格玛受体配体能够改善包括可卡因、冰毒、乙醇和尼古丁在内的多种滥用药物的特定行为效应。此外,最近的研究开始阐明西格玛-1 受体调节这些药物对神经传递、基因调控和神经可塑性影响的机制。总的来说,这些新发现表明,针对西格玛-1 受体的化合物可能代表一类潜在的新型治疗药物,旨在治疗药物滥用。涉及临床人群的未来研究对于验证西格玛-1 受体配体治疗物质滥用的治疗潜力至关重要。