Department of Forensic Medicine, Aarhus University, Denmark.
Department of Biomedicine, Aarhus University, Denmark.
Addict Biol. 2023 Sep;28(9):e13320. doi: 10.1111/adb.13320.
Fatal poisonings where both methadone and quetiapine are detected post-mortem occurs frequently in legal autopsy cases. It is unclear whether quetiapine increases the risk of fatal methadone poisoning or if it is merely detected due to widespread use. We hypothesized that methadone and quetiapine would have additive toxic effects on respiratory rate, blood pressure, and the QTc-interval. To investigate this hypothesis, we used telemetry implants for measurements of respiratory rate, haemodynamic variables, the velocity of blood pressure changes, temperature, and movement in conscious, freely moving male Wistar rats aged 12-13 weeks. The combined effects of three accumulative i.p. doses of methadone (2.5, 10, 15 mg/kg) and quetiapine (3, 10, 30 mg/kg) were compared to rats treated with the same doses of each drug alone, and a vehicle-treated group in a randomized investigator blinded study. No additive effects of quetiapine and methadone on respiratory rate, haemodynamic variables, or movement were observed. However, body temperature was significantly lower by approximately 1.5°C on average in the group treated with both methadone and quetiapine (15 + 30 mg/kg) compared to the other groups. This indicates a synergistic effect of quetiapine and methadone on thermoregulation, which may increase the risk of fatal poisoning. We suggest studying this finding further in human settings.
在法定尸检案例中，经常会发现同时检测到美沙酮和喹硫平的致命中毒。目前尚不清楚喹硫平是否会增加致命美沙酮中毒的风险，还是仅仅因为广泛使用而被检测到。我们假设美沙酮和喹硫平会对呼吸率、血压和 QTc 间期产生相加的毒性作用。为了验证这一假设，我们使用遥测植入物对 12-13 周龄雄性 Wistar 大鼠的呼吸率、血液动力学变量、血压变化速度、体温和运动进行了测量。在一项随机、研究者设盲的研究中，我们将三种累积腹腔注射剂量的美沙酮（2.5、10、15mg/kg）和喹硫平（3、10、30mg/kg）的联合作用与单独给予相同剂量的每种药物的大鼠以及给予载体的大鼠进行了比较。未观察到喹硫平和美沙酮对呼吸率、血液动力学变量或运动有相加作用。然而，与其他组相比，同时给予美沙酮和喹硫平（15+30mg/kg）的组的体温平均低约 1.5°C。这表明喹硫平和美沙酮在体温调节方面存在协同作用，这可能会增加致命中毒的风险。我们建议在人类环境中进一步研究这一发现。
