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酒精使用障碍的新兴药理学靶点

Emerging pharmacological targets for alcohol use disorder.

作者信息

Brockway Dakota F, Crowley Nicole A

机构信息

Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA; Penn State Neuroscience Institute, Penn State University, University Park, PA, 16802, USA.

Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA; Penn State Neuroscience Institute, Penn State University, University Park, PA, 16802, USA.

出版信息

Alcohol. 2024 Dec;121:103-114. doi: 10.1016/j.alcohol.2024.07.007. Epub 2024 Jul 26.

Abstract

Alcohol Use Disorder (AUD) remains a challenging condition with limited effective treatment options; however new technology in drug delivery and advancements in pharmacology have paved the way for discovery of novel therapeutic targets. This review explores emerging pharmacological targets that offer new options for the management of AUD, focusing on the potential of somatostatin (SST), vasoactive intestinal peptide (VIP), glucagon-like peptide-1 (GLP-1), nociceptin (NOP), and neuropeptide S (NPS). These targets have been selected based on recent advancements in preclinical and clinical research, which suggest their significant roles in modulating alcohol consumption and related behaviors. SST dampens cortical circuits, and targeting both the SST neurons and the SST peptide itself presents promise for treating AUD and various related comorbidities. VIP neurons are modulated by alcohol and targeting the VIP system presents an unexplored avenue for addressing alcohol exposure at various stages of development. GLP-1 interacts with the dopaminergic reward system and reduces alcohol intake. Nociceptin modulates mesolimbic circuitry and agonism and antagonism of nociceptin receptor offers a complex but promising approach to reducing alcohol consumption. NPS stands out for its anxiolytic-like effects, particularly relevant for the anxiety associated with AUD. This review aims to synthesize the current understanding of these targets, highlighting their potential in developing more effective and personalized AUD therapies, and underscores the importance of continued research in identifying and validating novel targets for treatment of AUD and comorbid conditions.

摘要

酒精使用障碍(AUD)仍然是一种具有挑战性的疾病,有效的治疗选择有限;然而,药物递送方面的新技术和药理学的进展为发现新的治疗靶点铺平了道路。本综述探讨了为AUD管理提供新选择的新兴药理学靶点,重点关注生长抑素(SST)、血管活性肠肽(VIP)、胰高血糖素样肽-1(GLP-1)、孤啡肽(NOP)和神经肽S(NPS)的潜力。这些靶点是根据临床前和临床研究的最新进展选择的,这些进展表明它们在调节酒精消费和相关行为方面具有重要作用。SST可抑制皮质回路,靶向SST神经元和SST肽本身为治疗AUD和各种相关合并症带来了希望。VIP神经元受酒精调节,靶向VIP系统为解决发育各阶段的酒精暴露提供了一条未被探索的途径。GLP-1与多巴胺能奖赏系统相互作用并减少酒精摄入量。孤啡肽调节中脑边缘回路,孤啡肽受体的激动和拮抗作用为减少酒精消费提供了一种复杂但有前景的方法。NPS因其类似抗焦虑的作用而突出,这与AUD相关的焦虑特别相关。本综述旨在综合目前对这些靶点的理解,强调它们在开发更有效和个性化的AUD治疗方法方面的潜力,并强调持续研究在识别和验证治疗AUD及合并症的新靶点方面的重要性。

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