Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan; Division of Cardiovascular Surgery, Department of Surgery, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.
Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
J Pharmacol Sci. 2020 Aug;143(4):330-332. doi: 10.1016/j.jphs.2020.05.008. Epub 2020 May 27.
We assessed torsadogenic action of risperidone, which can potently inhibit I as well as α-adrenoceptor. A toxic dose of 3 mg/kg of risperidone was intravenously administered over 10 min to chronic atrioventricular block dogs without anesthesia with monitoring Holter electrocardiogram (n = 4). Risperidone increased atrial/ventricular rate for 1-12 h/1-6 h and prolonged QTcF at 6 h after its administration, whereas it did not increase short-term variability of repolarization or induced torsade de pointes. These results suggest that α-adrenoceptor blockade-dependent, hypotension-induced, reflex-mediated increase of sympathetic tone by risperidone might play a role in protecting the heart from I inhibition-associated torsade de pointes.
我们评估了利培酮的致扭转型作用，它可以强烈抑制 I 型和 α-肾上腺素受体。将 3mg/kg 的利培酮有毒剂量在 10 分钟内静脉输注给未经麻醉的慢性房室传导阻滞犬，同时监测 Holter 心电图（n=4）。利培酮在给药后 1-12 小时/1-6 小时增加心房/心室率，并在给药后 6 小时延长 QTcF，但它不会增加复极短期变异性或引起尖端扭转型室性心动过速。这些结果表明，利培酮的 α-肾上腺素受体阻断依赖、低血压诱导、反射介导的交感神经张力增加可能在保护心脏免受 I 抑制相关的尖端扭转型室性心动过速方面发挥作用。
