Mishra Y, Ramzan I
Department of Pharmacy, University of Sydney, New South Wales, Australia.
Arch Int Pharmacodyn Ther. 1992 Jul-Aug;318:97-106.
The neuromuscular action of cimetidine, the prototype of H2 antagonists, was examined in urethane-anaesthetized and mechanically ventilated rats that were paralyzed with the non-depolarizing agent atracurium. Cimetidine, administered i.v. at doses of 3.2 to 56.2 mg/kg (13 to 223 microM/kg), produced an immediate potentiation of a steady 50% atracurium paralysis which was observed within 28 +/- 5 sec and which plateaued after 24 +/- 3 min. The dose of cimetidine that produced a 50% potentiation during peak effect was 14.5 mg/kg (58 microM/kg) and was associated with a serum cimetidine concentration of 47.5 micrograms/ml (or 188 microM). In a separate experiment, cimetidine, administered i.v. in a dose of 56.2 mg/kg (223 microM/kg), shifted the atracurium dose-effect curve to the left by 1.32-fold. Cimetidine alone, at either 10 or 100 mg/kg, did not affect the neuromuscular function by itself. These results suggest that high doses of cimetidine potentiate the neuromuscular paralysis induced with atracurium. This effect is opposite to that noted previously with ranitidine, a newer H2 antagonist which reverses atracurium neuromuscular paralysis in rats.
在使用非去极化剂阿曲库铵使大鼠麻痹的情况下，对H2拮抗剂原型西咪替丁的神经肌肉作用进行了研究，这些大鼠用乌拉坦麻醉并进行机械通气。静脉注射剂量为3.2至56.2mg/kg（13至223μM/kg）的西咪替丁，能立即增强稳定的50%阿曲库铵麻痹作用，在28±5秒内即可观察到，并在24±3分钟后达到平稳状态。在峰值效应期间产生50%增强作用的西咪替丁剂量为14.5mg/kg（58μM/kg），此时血清西咪替丁浓度为47.5μg/ml（或188μM）。在另一项实验中，静脉注射56.2mg/kg（223μM/kg）剂量的西咪替丁可使阿曲库铵剂量效应曲线向左移动1.32倍。单独使用10或100mg/kg的西咪替丁本身并不影响神经肌肉功能。这些结果表明，高剂量的西咪替丁可增强阿曲库铵诱导的神经肌肉麻痹作用。这种作用与先前观察到的雷尼替丁相反，雷尼替丁是一种较新的H2拮抗剂，可逆转大鼠的阿曲库铵神经肌肉麻痹作用。
