Gwee M C, Cheah L S, Shoon M L
Clin Exp Pharmacol Physiol. 1986 Aug;13(8):613-8. doi: 10.1111/j.1440-1681.1986.tb00946.x.
Responses of the toad isolated rectus abdominis muscle to cumulative doses of carbachol were recorded in the absence or presence of varying concentrations of cimetidine or ranitidine. The corresponding cumulative log concentration-response curves for carbachol were then plotted for each antagonist studied. Cimetidine (1 mmol/l) produced a straight and parallel 1.8-fold shift of the carbachol curve to the right of the corresponding control curve with no significant change in the maximal response. Cimetidine, at doses of 2.5 mmol/l and 5 mmol/l, and ranitidine, at doses of 0.1 mmol/l, 0.25 mmol/l and 0.5 mmol/l, produced a concentration-dependent and non-parallel shift of the carbachol curve to the right of the corresponding control curve accompanied by a marked decline of maximal responses. The results provide further evidence that ion-channel block may be involved in the neuromuscular blockade produced by cimetidine or ranitidine, the latter being more potent in this respect. Competitive antagonism may also be partly responsible for cimetidine-induced neuromuscular blockade, especially at lower drug concentrations.
在不存在或存在不同浓度西咪替丁或雷尼替丁的情况下，记录蟾蜍离体腹直肌对累积剂量卡巴胆碱的反应。然后针对每种研究的拮抗剂绘制卡巴胆碱相应的累积对数浓度-反应曲线。西咪替丁（1 mmol/L）使卡巴胆碱曲线相对于相应对照曲线向右产生了1.8倍的直线和平行移位，最大反应无显著变化。剂量为2.5 mmol/L和5 mmol/L的西咪替丁，以及剂量为0.1 mmol/L、0.25 mmol/L和0.5 mmol/L的雷尼替丁，使卡巴胆碱曲线相对于相应对照曲线向右产生浓度依赖性和非平行移位，同时最大反应显著下降。结果进一步证明离子通道阻滞可能参与了西咪替丁或雷尼替丁产生的神经肌肉阻滞，在这方面雷尼替丁作用更强。竞争性拮抗作用也可能部分导致西咪替丁引起的神经肌肉阻滞，尤其是在较低药物浓度时。
