Repurposing drugs for treatment of alcohol use disorder.

International review of neurobiology Pub Date : 2024-01-01 Epub Date: 2024-03-12 DOI:10.1016/bs.irn.2024.02.002
Henri-Jean Aubin
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Abstract

Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.

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将药物重新用于治疗酒精使用障碍。
将药物重新用于治疗酒精依赖涉及使用最初为其他疾病开发的药物,但这些药物在减少酒精使用或防止复发方面已显示出前景。这种方法比从头开始研发新药更具成本效益和时间效率。目前获准用于治疗酒精使用障碍(AUD)的药物包括阿坎酸、双硫仑、纳曲酮、纳美芬、巴氯芬和羟巴酸钠。阿坎酸是专门针对 AUD 开发的,而双硫仑的阻断酒精作用则是偶然发现的。纳曲酮和纳美芬最初被批准用于阿片类药物,但后来被二次应用于 AUD。巴氯芬(Baclofen)和羟苯酸钠(Sodium oxybate)则是从神经系统疾病中改造而来。其他药物也大有可为。抗惊厥药物托吡酯和唑尼沙胺显示出减少酒精消费的功效。另一种抗惊厥药加巴喷丁(gabapentin)的总体疗效令人失望,但涉及酒精戒断症状的病例除外。伐尼克兰是一种尼古丁受体激动剂,对不太严重的 AUD 或同时使用尼古丁的患者有益。昂丹司琼是一种 5-HT3 拮抗剂,对早发性 AUD 有潜在疗效,尤其是与纳曲酮合用时。阿立哌唑和喹硫平等抗精神病药物的疗效有限。α1肾上腺素能受体拮抗剂哌唑嗪和多沙唑嗪、糖皮质激素受体拮抗剂米非司酮、磷酸二酯酶抑制剂伊布司特、半胱氨酸原药N-乙酰半胱氨酸以及OX1R和OX2R阻断剂Suvorexant的潜在再利用还需要进一步研究。本综述支持将药物再利用作为扩大 AUD 治疗选择的有效策略。
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