急性术后疼痛和突发性癌症疼痛的药物仍然在临床上迫切需要。LPM3480392是μ-阿片受体的G蛋白偏向性配体，在非临床研究中显示出强效的镇痛作用。我们对健康的中国男性志愿者进行了两个LPM3480392的I期研究，以探讨其耐受性、药代动力学和药效动力学在单剂递增（研究I 0.1-3.0毫克，30分钟）和不同注射时间（研究II，0.6-1.0毫克，2-15分钟）下的影响。研究II中观察到了一起严重不良事件（AE），其余AE多为轻度或中度且在研究结束时解决。血浆LPM3480392最大浓度（Cmax）（在较低输注速率下）和血浆浓度时间曲线下面积（AUC）通常随剂量增加而增加。此外，以2分钟输注速率下的0.6毫克LPM3480392剂量能在10-30分钟内引起有效的镇痛效果，通过冷痛测试和瞳孔测量来衡量。这些研究结果表明，LPM3480392可能是急性疼痛管理的潜在治疗药物。本文受版权保护，版权所有。

Drugs for acute postoperative pain and breakthrough cancer pain are still urgent on clinical. LPM3480392 is a G-protein-biased ligand at the μ-opioid receptor and showed potent analgesia in nonclinical studies. Two phase I studies of LPM3480392 were conducted in healthy Chinese male volunteers to explore its tolerability, pharmacokinetics, and pharmacodynamics under single ascending doses (Study I 0.1-3.0 mg, 30 min) and different infusion time (Study II, 0.6-1.0 mg, 2-15 min). There was one serious adverse event (AE) observed in Study II, and the rest AEs were mild or moderate in severity and resolved by the end of the study. Plasma LPM3480392 maximum concentration (Cmax ) (under lower infusion rate) and area under the plasma concentration-time curve (AUCs) were generally increased with dose. Moreover, LPM3480392 at dose of 0.6 mg under 2 min infusion rate elicited effective analgesia as the peak effect within 10-30 min, which measured by cold pain test and pupillometry. These findings suggest that LPM3480392 could be a potential treatment for acute pain management.This article is protected by copyright. All rights reserved.