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拨快时钟:酒精依赖的潜在临床前和临床神经药理学靶点。

Turning the clock ahead: potential preclinical and clinical neuropharmacological targets for alcohol dependence.

机构信息

Center for Alcohol and Addiction Studies, Brown University Medical School, Providence, RI 02912, USA.

出版信息

Curr Pharm Des. 2010;16(19):2159-18. doi: 10.2174/138161210791516369.

Abstract

Treating alcohol use disorders represents a main goal in public health, but the effect of current medications is modest. Thus, in the last few years, research has been focusing on identifying new neuropharmacological targets for alcohol dependence. This review will summarize recent research, which has identified new targets to treat alcohol dependence. A variety of systems have been investigated, such as the endocannabinoid system, modulators of glutamatergic transmission, corticotropin-releasing factor (CRF), neuropeptide Y (NPY), nociceptin, glial cell line-derived neurotrophic factor (GDNF), acetaldehyde (ACD), substance P and Neurokinin 1 (NK1) receptor, nicotinic acetylcholine receptors (nAchRs), alpha-adrenergic receptor, and many others. Compared to preclinical studies, only a few clinical studies have been conducted so far. Thus, there is a critical need to translate successful preclinical results into human clinical trials. However, since some clinical studies have failed to replicate preclinical findings, future research will have not only to identify more efficacious medications, but also delineate the best match between a particular pharmacotherapy with a specific alcoholic subtype.

摘要

治疗酒精使用障碍是公共卫生的主要目标,但目前药物的疗效有限。因此,在过去几年中,研究一直集中在确定治疗酒精依赖的新神经药理学靶点上。这篇综述将总结最近的研究,这些研究已经确定了治疗酒精依赖的新靶点。已经研究了多种系统,如内源性大麻素系统、谷氨酸能传递调节剂、促肾上腺皮质释放因子 (CRF)、神经肽 Y (NPY)、孤啡肽、胶质细胞衍生神经营养因子 (GDNF)、乙醛 (ACD)、P 物质和神经激肽 1 (NK1)受体、烟碱型乙酰胆碱受体 (nAchRs)、α-肾上腺素能受体等。与临床前研究相比,到目前为止,只有少数临床研究已经进行。因此,迫切需要将成功的临床前结果转化为人类临床试验。然而,由于一些临床研究未能复制临床前的发现,未来的研究不仅要确定更有效的药物,还要确定特定的药物治疗与特定的酒精亚型之间的最佳匹配。

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