In-vitro Interaction between H2 Antagonists and Vecuronium

Abstract

Abstract The interaction between histamine H2 antagonists and the neuromuscular blocking drug vecuronium was investigated in the rat phrenic nerve-hemidiaphragm preparation. Cimetidine alone, in the concentration range 800–4000 μm produced between 14 and 74% neuromuscular paralysis with an EC50 (mean ± s.e.) of 2900 ± 100 μm. Ranitidine augmented the indirectly-evoked muscle response at concentrations between 30 and 160 μm but at higher concentrations, between 300 and 1800 μm, produced neuromuscular paralysis. Famotidine produced negligible and statistically insignificant (0–5%) neuromuscular paralysis at concentrations between 0·3 and 300 μm. Cimetidine (800 μm) shifted the neuromuscular concentration-effect curve of vecuronium to the left in a parallel manner, while ranitidine (160 μm) shifted it to the right. The potentiation ratio was 1·90 ± 0·14 for cimetidine and 0·62 ± 005 for ranitidine. Famotidine (30 μm) did not alter the response to vecuronium. These data indicate that higher than clinically relevant concentrations of cimetidine and ranitidine produce neuromuscular paralysis and may potentiate the action of vecuronium. Low concentrations of ranitidine may antagonize the action of vecuronium. Famotidine, in contrast, lacks significant neuromuscular effects.