Synthetic narcotics have been implicated as the single greatest contributor to increases opioid-related fatalities in recent years. This study evaluated mu-opioid-receptor (MOR) mediated-effects of seven fentanyl-related substances that have emerged in the recreational drug marketplace, and for which there are no existing or only limited in vivo data. Adult male Swiss Webster mice were administered fentanyl-related substances and their effects on nociception and locomotion as compared to MOR agonist standards were observed. In locomotor activity tests, morphine (100, 180 mg/kg), fentanyl (1, 10 mg/kg), beta-methylfentanyl (10 mg/kg), para-methoxyfentanyl (10 mg/kg), fentanyl carbamate (100 mg/kg), and 3-furanylfentanyl (10 mg/kg), elicited significant (p ≤ 0.05) dose-dependent increases in locomotion. However, para-methylfentanyl and beta′-phenylfentanyl did not produce significant effects on locomotion at doses up to 100 mg/kg and phenylfentanyl (100 mg/kg) significantly decreased locomotion. In warm water tail-withdrawal tests, all substances produced significant dose-dependent increases in antinociception with increasing ED₅₀ values (95% CI) of fentanyl [0.08 mg/kg (0.04–0.16)] > para-methoxyfentanyl [0.43 mg/kg (0.23–0.77)] > 3-furanylfentanyl [0.51 mg/kg (0.36–0.74)] > beta-methylfentanyl [0.74 mg/kg (0.64–0.85)] > para-methylfentanyl [1.92 mg/kg (1.48–2.45)] > fentanyl carbamate [5.59 mg/kg (4.11–7.54)] > morphine [7.82 mg/kg (5.42–11.0)] > beta′-phenylfentanyl [19.4 mg/kg (11.0–34.4)] > phenylfentanyl [55.2 mg/kg (33.5–93.0)]. Naltrexone (1 mg/kg) increased ED₅₀ values several fold with decreasing magnitudes of para-methylfentanyl (63.1×) > para-methoxyfentanyl (22.5×) > beta′-phenylfentanyl (21.0×) > 3-furanylfentanyl (20.6×) > beta-methylfentanyl (19.2×) > phenylfentanyl (5.23×) > fentanyl (3.95×) > fentanyl carbamate (2.21×) > morphine (1.48×). These findings expand upon in vivo results from previous studies and establish that the effects of these fentanyl related-related substances are at least in part mediated by the MOR.

近年来，合成麻醉品被认为是导致阿片类药物相关死亡人数增加的最大因素。本研究评估了消遣性药物市场中出现的七种芬太尼相关物质的 mu-阿片受体 (MOR) 介导的作用，并且没有现有的或仅有有限的体内数据。成年雄性瑞士韦伯斯特小鼠被给予芬太尼相关物质，并观察到与 MOR 激动剂标准相比它们对伤害感受和运动的影响。在运动活动测试中，吗啡 (100, 180 mg/kg)、芬太尼 (1, 10 mg/kg)、β-甲基芬太尼 (10 mg/kg)、对甲氧基芬太尼 (10 mg/kg)、氨基甲酸芬太尼 (100 mg /kg) 和 3-呋喃基芬太尼 (10 mg/kg)，引起显着 ( p ≤ 0.05) 运动的剂量依赖性增加。然而，对-甲基芬太尼和β'-苯基芬太尼在高达 100 mg/kg 的剂量下对运动没有显着影响，而苯基芬太尼 (100 mg/kg) 显着降低运动。在温水退尾试验中，随着芬太尼的 ED ₅₀值 (95% CI) [0.08 mg/kg (0.04–0.16)] > 对甲氧基芬太尼 [0.43 mg/kg (0.23–0.77)] > 3-呋喃芬太尼 [0.51 mg/kg (0.36–0.74)] > β-甲基芬太尼 [0.74 mg/kg (0.64–0.85)] > 对-甲基芬太尼 [1.92 mg/kg (1.48–2.45)] > 氨基甲酸芬太尼 [5.59 mg/kg (4.11–7.54)] > 吗啡 [7.82 mg/kg (5.42–11.0)] > β'-苯基芬太尼 [19.4 mg/kg (11.0–34.4)] > 苯基芬太尼 [55.2 mg/kg (33.5–93.0)]。纳曲酮 (1 mg/kg) 随着对-甲基芬太尼 (63.1×) > 对-甲氧基芬太尼 (22.5×) > β'-苯基芬太尼 (21.0×) > 3-呋喃芬太尼 (20.6×) >幅度的降低，ED ₅₀值增加数倍β-甲基芬太尼（19.2×）>苯基芬太尼（5.23×）>芬太尼（3.95×）>氨基甲酸芬太尼（2.21×）>吗啡（1.48×）。这些发现扩展了先前研究的体内结果，并确定这些芬太尼相关物质的作用至少部分由 MOR 介导。