Interaction between succinylcholine and ranitidine in rats

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) μg · 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.