Interaction between succinylcholine and ranitidine in rats

Abstract

The hypothesis that the histamine H2 receptor blocker ranitidine potentiates neuromuscular paralysis during anaesthesia was tested in vivo in urethane anaesthetised and mechanically ventilated rats. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 48.5% (+/- 2.5 SEM) tibialis anterior muscle paralysis in 14 rats. Ranitidine 2.5, 5, 10, or 20 mg.kg-1 iv, was then administered into groups of three or five rats. Ranitidine produced an immediate potentiation of neuromuscular paralysis followed by a transient reversal and then a continued steady-state potentiation. Peak potentiation occurred within 20 (+/- 3.3) sec and was maintained in all the rats to steady-state. Peak reversal was evident 70 (+/- 8.1) sec after ranitidine administration. There was an excellent relationship (r2 = 0.98, P < 0.001) between peak potentiation and serum ranitidine concentration with 50% potentiation occurring at 25.8 (+/- 1.1) micrograms.ml-1. There was a weak relationship (r2 = 0.39, P < 0.05) between peak reversal and serum ranitidine but potentiation at steady-state was not correlated to serum ranitidine concentration (r2 = 0.19, P > 0.05). These results show that ranitidine alters the neuromuscular action of succinylcholine in rats in a similar manner to cimetidine.