Drugs targeting the μ-opioid receptor (MOR) remain the most efficacious analgesics for the treatment of pain, but activation of MOR with current opioid analgesics also produces harmful side effects, notably physical dependence, addiction, and respiratory depression. Opioid peptides have been accepted as promising candidates for the development of safer and more efficacious analgesics. To develop peptide-based opioid analgesics, strategies such as modification of endogenous opioid peptides, development of multifunctional opioid peptides, G protein-biased opioid peptides, and peripherally restricted opioid peptides have been reported. This review seeks to provide an overview of the opioid peptides that produce potent antinociception with much reduced side effects in animal models and highlight the potential advantages of peptides as safer opioid analgesics.

中文翻译：

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用于发现更安全的阿片类镇痛药的肽衍生配体


针对μ阿片受体（MOR）的药物仍然是治疗疼痛最有效的镇痛药，但目前的阿片类镇痛药激活MOR也会产生有害的副作用，特别是身体依赖性、成瘾和呼吸抑制。阿片肽已被认为是开发更安全、更有效的镇痛药的有希望的候选者。为了开发基于肽的阿片类镇痛药，已经报道了诸如修饰内源性阿片类肽、开发多功能阿片类肽、G蛋白偏向的阿片类肽和外周限制性阿片类肽等策略。本综述旨在概述阿片类肽，这些肽在动物模型中产生有效的镇痛作用，同时大大减少副作用，并强调肽作为更安全的阿片类镇痛药的潜在优势。