Neuromuscular blocking profile of the vecuronium analogue, Org‐9487, in the rat isolated hemidiaphragm preparation

Prior, Chris; Tian, Lijun; Mallah, Ahmed I. El; Young, Louise; Ward, John

doi:10.1111/j.1476-5381.1995.tb15962.x

Cited by 8 publications

(1 citation statement)

References 29 publications

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“…These results were in agreement with those of Prior et al . [24] in the rat diaphragm, although in this species higher concentrations of the muscle relaxants were required to produce neuromuscular block. Greater steric hindrance, resulting from the presence of a bulky 17‐propionate substituent on the D‐ring of the steriod, may provide an explanation for the low binding affinity of Org 9487.…”

Section: Introductionmentioning

confidence: 92%

Neuromuscular blocking and cardiovascular effects of Org 9487, a new short-acting aminosteroidal blocking agent, in anaesthetized animals and in isolated muscle preparations

Muir¹,

Sleigh²,

Marshall³

et al. 1998

Eur J Anaesthesiol

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This study was undertaken to investigate the neuromuscular blocking profile and cardiovascular effects of Org 9487, a new aminosteroidal, non-depolarizing, neuromuscular blocking agent structurally related to vecuronium, in anaesthetized animals and in isolated muscle preparations. In in vitro functional assays of neuromuscular blocking activity, Org 9487 was between eight and 15 times less potent than vecuronium. In cats and monkeys the potency of Org 9487 was approximately one-seventh and one-twentieth, respectively, that of vecuronium. In both species, Org 9487 induced rapidly developing (onset times between 1.5 min and 1.9 min) neuromuscular paralysis, which was shorter-lasting than that of vecuronium and similar in time course to suxamethonium. The vagal: neuromuscular blocking dose ratio for Org 9487 was 3 and ganglion block was seen only at approximately 20 times the neuromuscular blocking dose. There was no evidence in the rat that Org 9487, administered at doses up to 3 mg kg-1, inhibited noradrenaline re-uptake. In anaesthetized dogs, Org 9487 (3 x 90% blocking dose) induced only relatively small and transient haemodynamic effects. The administration of clinically relevant doses of neostigmine or pyridostigmine shortened the time-course profile of Org 9487, even when administered during profound neuromuscular block. In animals, Org 9487 is a low potency, nondepolarizing neuromuscular blocking agent with a time course profile similar to that of suxamethonium. Although Org 9487 is less selective than vecuronium for the neuromuscular junction, it is unlikely to produce prohibitive cardiovascular side effects in man.

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Section: Introductionmentioning

confidence: 92%