Enhancement by cimetidine of neuromuscular paralysis induced with atracurium in rats.
The neuromuscular action of cimetidine, the prototype of H2 antagonists, was examined in urethane-anaesthetized and mechanically ventilated rats that were paralyzed with the non-depolarizing agent atracurium. Cimetidine, administered i.v. at doses of 3.2 to 56.2 mg/kg (13 to 223 microM/kg), produced an immediate potentiation of a steady 50% atracurium paralysis which was observed within 28 +/- 5 sec and which plateaued after 24 +/- 3 min. The dose of cimetidine that produced a 50% potentiation during peak effect was 14.5 mg/kg (58 microM/kg) and was associated with a serum cimetidine concentration of 47.5 micrograms/ml (or 188 microM). In a separate experiment, cimetidine, administered i.v. in a dose of 56.2 mg/kg (223 microM/kg), shifted the atracurium dose-effect curve to the left by 1.32-fold. Cimetidine alone, at either 10 or 100 mg/kg, did not affect the neuromuscular function by itself. These results suggest that high doses of cimetidine potentiate the neuromuscular paralysis induced with atracurium. This effect is opposite to that noted previously with ranitidine, a newer H2 antagonist which reverses atracurium neuromuscular paralysis in rats.
Mishra
Y
Y
Department of Pharmacy, University of Sydney, New South Wales, Australia.
Ramzan
I
I
D000818:Animals; D001279:Atracurium / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007262:Infusions, Intravenous; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D010243:Paralysis / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001279:Atracurium; D002927:Cimetidine