Biased activation of G-protein-coupled receptors (GPCRs) is shifting drug discovery efforts and appears promising for the development of safer drugs. The most effective analgesics to treat acute pain are agonists of the μ opioid receptor (μ-OR), a member of the GPCR superfamily. However, the analgesic use of opioid drugs, such as morphine, is hindered by adverse effects. Only a few μ-OR agonists have been reported to selectively activate the G_i over β-arrestin signaling pathway, resulting in lower gastrointestinal dysfunction and respiratory suppression. Here, we discuss the strategies that led to the development of biased μ-OR agonists, and potential areas for improvement, with an emphasis on structural aspects of the ligand–receptor recognition process.

G蛋白偶联受体（GPCR）的偏向激活正在改变药物发现的努力，并有望开发出更安全的药物。治疗急性疼痛最有效的镇痛药是GPCR超家族成员μ阿片受体（μ-OR）的激动剂。但是，阿片类药物（如吗啡）的镇痛作用受到不良影响。据报道，仅有少数μ-OR激动剂通过β-arrestin信号传导途径选择性激活G _i，从而降低胃肠道功能障碍和呼吸抑制。在这里，我们讨论导致偏向μ-OR激动剂发展的策略和潜在的改进领域，重点是配体-受体识别过程的结构方面。