United States Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Rd, Aberdeen Proving Ground, MD, 21010, United States.
United States Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Rd, Aberdeen Proving Ground, MD, 21010, United States.
Toxicol Lett. 2020 Jun 1;325:34-42. doi: 10.1016/j.toxlet.2020.02.008. Epub 2020 Feb 15.
Carfentanil is an ultra-potent opioid with an analgesic potency 10,000 times that of morphine but has received little scientific investigation. Three experiments were conducted to evaluate the toxicity of carfentanil and the efficacy of naloxone in adult male African green monkeys. The first experiment determined the ED (found to be 0.71 μg/kg) of subcutaneous carfentanil for inducing bradypnea and/or loss of posture. Experiment 2 attempted to establish the ED of naloxone for rapidly reversing the bradypnea/loss of posture induced by carfentanil (1.15 μg/kg). Experiment 3 evaluated the effects of carfentanil (0.575 μg/kg) alone, the safety of naloxone (71-2841 μg/kg), and the efficacy of naloxone (71-710 μg/kg) administration at two time points following carfentanil (1.15 μg/kg) on operant choice reaction time. Collectively, these experiments characterized the temporal progression of carfentanil-induced toxic signs, determined the range of naloxone doses that restored respiratory and gross behavioral function, and determined the time course and range of naloxone doses that partially or completely reversed the effects of carfentanil on operant choice reaction time performance in African green monkeys. These results have practical relevance for the selection of opioid antagonists, initial doses, and expected functional outcomes following treatment of synthetic opioid overdose in a variety of operational/emergency response contexts.
卡芬太尼是一种超强效阿片类药物，其镇痛效力是吗啡的 10000 倍，但几乎没有得到科学研究。进行了三项实验来评估卡芬太尼的毒性和纳洛酮在成年雄性绿猴中的疗效。第一项实验确定了皮下给予卡芬太尼引起呼吸缓慢和/或姿势丧失的 ED（发现为 0.71μg/kg）。实验 2 试图确定纳洛酮逆转卡芬太尼（1.15μg/kg）引起的呼吸缓慢/姿势丧失的 ED（1.15μg/kg）。实验 3 评估了卡芬太尼（0.575μg/kg）单独作用、纳洛酮（71-2841μg/kg）的安全性以及纳洛酮（71-710μg/kg）在给予卡芬太尼（1.15μg/kg）后两个时间点的疗效对操作选择反应时间的影响。这些实验共同描述了卡芬太尼引起的毒性体征的时间进程，确定了恢复呼吸和大体行为功能的纳洛酮剂量范围，并确定了部分或完全逆转纳洛酮对操作选择反应时间的影响的时间过程和纳洛酮剂量范围在绿猴中的作用。这些结果对于在各种操作/紧急响应情况下治疗合成阿片类药物过量时选择阿片类拮抗剂、初始剂量和预期功能结果具有实际意义。
