Mishra Y, Ramzan I
Pharmacy Department, University of Sydney, New South Wales, Australia.
Can J Anaesth. 1992 Apr;39(4):370-4. doi: 10.1007/BF03009048.
The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (+/- 1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 10, 17.8, 23.7, 31.6, or 56.2 mg.kg-1 was then administered in groups of two to three rats. Cimetidine produced an immediate potentiation of twitch suppression followed by a transient reversal and then a continued potentiation. Peak potentiation occurred within 19.0 (+/- 2.7) sec and was maintained in 11 rats at steady-state. Reversal was evident 4.1 (+/- 0.4) min after cimetidine administration. There was a good relationship between peak potentiation and serum cimetidine concentration with 50% potentiation occurring at 46.5 (+/- 4.6) micrograms.ml-1. Potentiation at steady-state was not correlated to serum cimetidine concentration but there was a weak relationship between reversal and serum cimetidine concentration. These results support reports from patients of an interaction between cimetidine and succinylcholine.
在机械通气的情况下，对氨基甲酸乙酯麻醉的大鼠进行了体内实验，以验证组胺H2受体阻断对神经肌肉功能产生不利影响这一假设。对19只大鼠静脉注射大剂量琥珀酰胆碱，并持续恒速输注以维持49.2%（±1.5标准误）的抽搐抑制。然后，将西咪替丁以3.2、7.5、10、17.8、23.7、31.6或56.2mg·kg-1的剂量静脉注射给两到三只大鼠为一组。西咪替丁立即增强了抽搐抑制作用，随后出现短暂的逆转，然后持续增强。最大增强作用在19.0（±2.7）秒内出现，并在11只大鼠中维持在稳态。西咪替丁给药后4.1（±0.4）分钟出现明显的逆转。最大增强作用与血清西咪替丁浓度之间存在良好的关系，当血清西咪替丁浓度为46.5（±4.6）μg·ml-1时出现50%的增强作用。稳态时的增强作用与血清西咪替丁浓度无关，但逆转与血清西咪替丁浓度之间存在微弱的关系。这些结果支持了关于西咪替丁与琥珀酰胆碱相互作用的患者报告。
