Emerging pharmacological targets for alcohol use disorder

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol Pub Date : 2024-07-26 DOI:10.1016/j.alcohol.2024.07.007

Dakota F. Brockway , Nicole A. Crowley

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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.

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治疗酒精使用障碍的新药理目标。

酒精使用障碍（AUD）仍然是一种具有挑战性的疾病，有效的治疗方案有限；然而，新的给药技术和药理学的进步为发现新的治疗靶点铺平了道路。本综述探讨了为治疗 AUD 提供新选择的新兴药理学靶点，重点关注体生长抑素 (SST)、血管活性肠肽 (VIP)、胰高血糖素样肽-1 (GLP-1)、神经肽 (NOP) 和神经肽 S (NPS) 的潜力。选择这些靶点的依据是临床前和临床研究的最新进展，这些进展表明它们在调节酒精消费和相关行为方面发挥着重要作用。SST 可抑制大脑皮层回路，以 SST 神经元和 SST 肽本身为靶点有望治疗 AUD 和各种相关合并症。VIP神经元受酒精调节，针对VIP系统的研究为解决不同发育阶段的酒精暴露问题提供了一条尚未探索的途径。GLP-1 与多巴胺能奖赏系统相互作用，减少酒精摄入。痛觉素能调节间叶回路，痛觉素受体的激动和拮抗作用为减少酒精摄入提供了一种复杂但有前景的方法。NPS 具有类似抗焦虑的作用，尤其适用于与 AUD 相关的焦虑症。本综述旨在综述目前对这些靶点的认识，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，并强调继续开展研究以确定和验证治疗 AUD 和合并症的新靶点的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alcohol 医学-毒理学

CiteScore

4.60

自引率

4.30%

发文量

审稿时长

15.6 weeks

期刊介绍： Alcohol is an international, peer-reviewed journal that is devoted to publishing multi-disciplinary biomedical research on all aspects of the actions or effects of alcohol on the nervous system or on other organ systems. Emphasis is given to studies into the causes and consequences of alcohol abuse and alcoholism, and biomedical aspects of diagnosis, etiology, treatment or prevention of alcohol-related health effects. Intended for both research scientists and practicing clinicians, the journal publishes original research on the neurobiological, neurobehavioral, and pathophysiological processes associated with alcohol drinking, alcohol abuse, alcohol-seeking behavior, tolerance, dependence, withdrawal, protracted abstinence, and relapse. In addition, the journal reports studies on the effects alcohol on brain mechanisms of neuroplasticity over the life span, biological factors associated with adolescent alcohol abuse, pharmacotherapeutic strategies in the treatment of alcoholism, biological and biochemical markers of alcohol abuse and alcoholism, pathological effects of uncontrolled drinking, biomedical and molecular factors in the effects on liver, immune system, and other organ systems, and biomedical aspects of fetal alcohol spectrum disorder including mechanisms of damage, diagnosis and early detection, treatment, and prevention. Articles are published from all levels of biomedical inquiry, including the following: molecular and cellular studies of alcohol''s actions in vitro and in vivo; animal model studies of genetic, pharmacological, behavioral, developmental or pathophysiological aspects of alcohol; human studies of genetic, behavioral, cognitive, neuroimaging, or pathological aspects of alcohol drinking; clinical studies of diagnosis (including dual diagnosis), treatment, prevention, and epidemiology. The journal will publish 9 issues per year; the accepted abbreviation for Alcohol for bibliographic citation is Alcohol.