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低成瘾性阿片类镇痛药物研发现状和趋势OA北大核心CSTPCD

Developments of opioid analgesics with low addiction potential

中文摘要英文摘要

阿片类药物在疼痛治疗中发挥重要作用,但其在有效控制各类型急性和慢性疼痛的同时,也带来非医疗目的用药和药物成瘾的风险,造成阿片类药物危机.阿片受体在中枢神经系统广泛分布,介导复杂的生物学效应.阿片类镇痛药物的不良反应如呼吸抑制、依赖和成瘾等严重限制了其临床应用.目前,低成瘾性阿片类镇痛药物研发策略主要包括防滥用新制剂、靶向外周的阿片受体激动剂、阿片受体G蛋白信号通路偏向性激动剂、阿片受体异聚体激动剂和阿片受体多功能配体等,大部分正在进行非临床或临床研究,有一些新制剂药物已经上市.但这些措施在产生镇痛或其他治疗益处的同时,仍在一定程度上保留了传统阿片类镇痛药物的潜在滥用风险和其他不良反应,如何将镇痛作用与成瘾潜能完全分离面临重大挑战.因此,新型低成瘾性阿片类镇痛药物的研发仍需更多努力.

Opioid analgesics play an important role in pain management.While opioid analgesics have been used to control various types of acute and chronic pain,they bring about the risks of non-medical use and addiction,which results in a worldwide opioid crisis.Opioid receptors are widely distributed in the central nervous system and mediate complex biological effects.The side effects of opioid analgesics,such as respiratory depression,dependence and addiction,have severely limited their clinical applications.The main strategies for developing new opioid analgesics with low addiction potential involve abuse-deterrent formulations,agonists targeting peripheral opioid receptors,G protein signaling-biased agonists of opioid receptors,agonists targeting opioid receptor heteromers and multi-functional ligands of opioid receptors.Most of them are undergoing clinical or pre-clinical research,and some new formulation medicines have been approved for marketing.Despite the analgesic or other therapeutic benefits,these strategies retain to some extent the potential risk of abuse and other adverse effects like to traditional opioid analgesics.How to fully separate the analgesic action from addiction potential remains challenging.Therefore,more efforts are needed to develop new opioid anal-gesics with low addiction potential.

王志媛;吴宁

军事医学研究院,北京 100850

药学

阿片类镇痛药物疼痛治疗药物滥用防滥用制剂偏向激动异聚体多功能配体

opioid analgesicspaintreatmentdrug abuseabuse-deterrent opioid formulationsbiased agonismheteromersmulti-functional ligands

《中国药理学与毒理学杂志》 2024 (007)

481-495 / 15

国家自然科学基金(81874310) National Natural Science Foundation of China(81874310)

10.3867/j.issn.1000-3002.2024.07.001

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