The effects of a 16-N-homopiperidino analogue of vecuronium on neuromuscular transmission in anaesthetized cats, pigs, dogs and monkeys, and in isolated preparations.

Abstract

Org 9991, a 16-N-homopiperidinium substituted vecuronium analogue, has been tested for neuromuscular blocking activity in anaesthetized cats, pigs, dogs and monkeys, and in isolated nerve-muscle preparations. Org 9991 exhibited non-depolarizing neuromuscular blocking activity of the competitive type, being reversible by neostigmine and showing no endplate channel blocking action in isolated preparations. In cats, 50% vagal block was observed at doses of Org 9991 approximately 10 times those producing 50% neuromuscular block; no ganglion block was seen at these doses. Effects on blood pressure or heart rate at 90% twitch blocking doses were either minor or absent. The potency and time course of action of Org 9991 remained similar in all four species: i.e. 90% block at ca 200-300 micrograms kg-1; onset time ca 1.2-1.9 min; duration 90% ca 4.5-8.9 min. This study suggests that 16-N-homopiperidinium analogues of vecuronium may provide leads in the quest for a potent non-depolarizing replacement for suxamethonium.