The effects of a 16-N-homopiperidino analogue of vecuronium on neuromuscular transmission in anaesthetized cats, pigs, dogs and monkeys, and in isolated preparations.
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.
Muir
A W
AW
Department of Pharmacology, Organon Laboratories Ltd., Newhouse, Lanarkshire, UK.
Anderson
K
K
Marshall
R J
RJ
Booij
L H
LH
Crul
J F
JF
Prior
C
C
Bowman
W C
WC
Marshall
I G
IG
D000732:Androstanols / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D002415:Cats; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D009435:Synaptic Transmission / Q000187:drug effects
D000732:Androstanols; D009466:Neuromuscular Blocking Agents; C063470:ORG 9991