Chen Yuanyuan, Lai Miaojun, Li Xiangyu, Qiao Yanling, Xu Deli, Fu Dan, Di Bin, Xu Peng
School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
Office of China National Narcotics Control Commission, Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Beijing, 100193, China.
Psychopharmacology (Berl). 2025 Apr 17. doi: 10.1007/s00213-025-06790-2.
Furanylfentanyl and tetrahydrofuranylfentanyl (THF-F) have been emerging in numerous intoxication and overdose cases in recent years. However, there remains a data deficiency regarding the abuse potential of these novel fentanyl analogs.
This study was designed to systematically assess the abuse potential of furanylfentanyl and THF-F.
In this study, we evaluated the abuse potential of furanylfentanyl and THF-F via the conditioned place preference (CPP), drug self-administration, drug discrimination, and naloxone-precipitated withdrawal experiments with fentanyl as a reference.
Results from CPP experiments indicated that furanylfentanyl and THF-F could induce CPP at minimum doses of 0.1 mg/kg and 3 mg/kg, respectively. These doses were 1 time and 30 times that of fentanyl (0.1 mg/kg). Furanylfentanyl elicited stable self-administration responses at 2.5 µg/kg/infusion, whereas THF-F did so at 50 µg/kg/infusion. In the drug-substitution test, furanylfentanyl and THF-F induced the maximum number of infusions at 1.10 µg/kg and 12.5 µg/kg, respectively, which were 1 time and 10 times that of fentanyl (1.21 µg/kg). In drug discrimination tests, all three substances were fully substituted for the discriminative-stimulus effects of heroin dose-dependently. The substitution potency of furanylfentanyl (ED = 2.68 µg/kg) was similar to that of fentanyl (ED = 2.66 µg/kg), while THF-F (ED = 36.32 µg/kg) was 14-fold less potent than fentanyl. Repeated administration of furanylfentanyl and THF-F produced naloxone-precipitated withdrawal symptoms. Thus, furanylfentanyl exhibited comparable potency to fentanyl in terms of rewarding, reinforcing, and subjective effects, while THF-F had reduced potency in these effects. Both of them had physical dependence.
Taken together, our study presented new evidence indicating that furanylfentanyl and THF-F exhibit significant abuse potential in rodent models, which provides experimental data for the control. Furthermore, our study offered valuable information for future studies into the addictive properties of structurally modified fentanyl analogs.
近年来，呋喃基芬太尼和四氢呋喃基芬太尼（THF-F）在众多中毒和过量用药案例中不断出现。然而，关于这些新型芬太尼类似物的滥用潜力，仍存在数据不足的情况。
本研究旨在系统评估呋喃基芬太尼和THF-F的滥用潜力。
在本研究中，我们以芬太尼为参照，通过条件性位置偏爱（CPP）、药物自我给药、药物辨别和纳洛酮诱发戒断实验，评估了呋喃基芬太尼和THF-F的滥用潜力。
CPP实验结果表明，呋喃基芬太尼和THF-F分别在最低剂量0.1mg/kg和3mg/kg时可诱发CPP。这些剂量分别是芬太尼（0.1mg/kg）的1倍和30倍。呋喃基芬太尼在2.5μg/kg/输注时引发稳定的自我给药反应，而THF-F在50μg/kg/输注时引发该反应。在药物替代试验中，呋喃基芬太尼和THF-F分别在1.10μg/kg和12.5μg/kg时诱发最大输注次数，分别是芬太尼（1.21μg/kg）的1倍和10倍。在药物辨别试验中，所有三种物质均能剂量依赖性地完全替代海洛因的辨别性刺激效应。呋喃基芬太尼（ED = 2.68μg/kg）的替代效力与芬太尼（ED = 2.66μg/kg）相似，而THF-F（ED = 36.32μg/kg）的效力比芬太尼低14倍。重复给予呋喃基芬太尼和THF-F会产生纳洛酮诱发的戒断症状。因此，呋喃基芬太尼在奖赏、强化和主观效应方面表现出与芬太尼相当的效力，而THF-F在这些效应方面效力降低。它们都具有身体依赖性。
综上所述，我们的研究提供了新的证据，表明呋喃基芬太尼和THF-F在啮齿动物模型中具有显著的滥用潜力，这为控制提供了实验数据。此外，我们的研究为未来关于结构修饰的芬太尼类似物成瘾特性的研究提供了有价值的信息。
