背景:异丁酰基-卡芬太尼是最新发现的芬太尼类似物,其化学结构与卡芬太尼相似。它的模拟,卡芬太尼,被认为是世界上最致命的药物之一,效力是吗啡的一万倍.因此,异丁酰基-卡芬太尼可能具有相当高的效力,其有害作用不容忽视。
目的:本研究旨在评估异丁酰基-卡芬太尼的镇痛效果及其误用的潜在风险。
方法:在本研究中,我们通过上下程序评估异丁酰基-卡芬太尼的急性毒性,镇痛效果通过热板试验,条件位置偏好(CPP)的滥用潜力,药物自我给药,和药物歧视测试,并将其与芬太尼和卡芬太尼进行了比较。
结果:异丁酰基-卡芬太尼的估计中位致死剂量(LD50)为175mg/kg(胃内给药,IG),15.84mg/kg(腹腔注射,IP),15.84mg/kg(皮下注射,SC),和1.6mg/kg(静脉注射,IV),分别。异丁酰基-卡芬太尼的50%最大镇痛效果(ED50)测定为0.00319mg/kg,镇痛效力是芬太尼的14倍,是卡芬太尼的0.82倍。异丁酰基-卡芬太尼在0.1mg/kg的最小剂量下表现出明显的位置偏好,而芬太尼在最小剂量为0.3mg/kg时表现出明显的位置偏好。在海洛因(0.05mg/kg/输注)自我给药替代实验中,异丁酰基-卡芬太尼在0.0005-0.001mg/kg/输注剂量时表现出明显的自我给药行为,以0.001mg/kg的剂量观察到的最大输注次数。在海洛因(1mg/kg)的药物辨别实验中,芬太尼(0.005-0.02mg/kg),卡芬太尼(0.0005-0.002mg/kg),和异丁酰基-卡芬太尼(0.001-0.005mg/kg)在剂量-效应曲线中进行测试。结果表明,所有三种药物均表现出剂量依赖性增加的与药物相关的鼻子戳反应的数量和减少的鼻子戳的速度。发现异丁酰基-卡芬太尼的主观效果效力是芬太尼的4.4倍和卡芬太尼的0.5倍。
结论:总之,异丁酰基-卡芬太尼具有较高的急性毒性和镇痛作用,具有很强的心理依赖性,大约是芬太尼的5倍和卡芬太尼的0.5倍,并具有极高的滥用效力。
BACKGROUND: Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored.
OBJECTIVE: This study was designed to assess the analgesic effect of isobutyryl-carfentanyl and the potential risks associated with its misuse.
METHODS: In this study, we assessed the acute toxicity of isobutyryl-carfentanyl by up-and-down-procedure, the analgesic efficacy by hot-plate test, the abuse potential by conditioned place preference (CPP), drug self-administration, and drug discrimination tests, and compared it with fentanyl and carfentanyl.
RESULTS: The estimated median lethal dose (LD50) of isobutyryl-carfentanyl administered were 175 mg/kg (intragastric administration, IG), 15.84 mg/kg (intraperitoneal injection, IP), 15.84 mg/kg (subcutaneous injection, SC), and 1.6 mg/kg (intravenous injection, IV), respectively. The 50% maximal analgesic effect (ED50) of isobutyryl-carfentanyl was determined to be 0.00319 mg/kg, with an analgesic potency 14 times that of fentanyl and 0.82 times that of carfentanyl. Isobutyryl-carfentanyl exhibited a significant positional preference at a minimum dose of 0.1 mg/kg, while fentanyl exhibited a significant positional preference at a minimum dose of 0.3 mg/kg. In the heroin (0.05 mg/kg/infusion) self-administration substitution experiment, isobutyryl-carfentanyl showed significant self-administration behaviour at doses of 0.0005-0.001 mg/kg/infusion, with the maximum number of infusions observed at a dose of 0.001 mg/kg. In the heroin (1 mg/kg) drug discrimination experiment, fentanyl (0.005-0.02 mg/kg), carfentanyl (0.0005-0.002 mg/kg), and isobutyryl-carfentanyl (0.001-0.005 mg/kg) were tested in the dose-effect curves. The results showed that all three drugs exhibit dose-dependent increase in the number of drug-associated nose pokes responses and reduction in the rate of nose pokes. The subjective effect potency of isobutyryl-carfentanyl was found to be 4.4 times that of fentanyl and 0.5 times that of carfentanyl.
CONCLUSIONS: In summary, isobutyryl-carfentanyl has high acute toxicity and analgesic effect, with strong psychological dependence approximately 5 times that of fentanyl and 0.5 times that of carfentanyl, and has extremely high abuse potency.