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British Journal of Anaesthesia, 1989, Vol. 63, No. 4 400-410
© 1989 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

EFFECTS OF A NEW NEUROMUSCULAR BLOCKING AGENT (ORG 9426) IN ANAESTHETIZED CATS AND PIGS AND IN ISOLATED NERVE-MUSCLE PREPARATIONS

A. W. MUIR, M.I.BIOL., J. HOUSTON, M.I.BIOL., M.SC., K. L. GREEN, B.SC., PH.D.*, R. J. MARSHALL, B.SC., PH.D., W. C. BOWMAN, PH.D., D.SC. and I. G. MARSHALL, B.SC., PH.D.

Department of Pharmacology, Organon Scientific Development Group, Organon Laboratories Ltd Newhouse, Lanarkshire ML1 5SH
Department of Physiology and Pharmacology, University of Strathclyde Glasgow G1 1XW

*Present address: Department of Pharmacology, University of Edinburgh, Edinburgh EH8 9JZ.

Correspondence to I.G.M.

The effects of Org 9426 (the 2-morpholino, 3-hydroxy, 16N-allyl pyrrolidino analogue of vecuronium) were studied in anaesthetized cats and pigs and in isolated nerve—muscle preparations using tension and intracellular recording techniques. In isolated preparations, the effects of Org 9426 were antagonized by neostigmine. No contracture of the chick muscle preparation occurred. Org 9426 reduced the amplitude of endplate currents (EPC) in rat and snake muscle, but had no major effects on EPC decay characteristics, indicating a lack of endplate channel blocking action. In anaesthetized animals, no fasciculations were observed and the neuromuscular block was associated with tetanic and train-of-four fade and was antagonized by neostigmine. In anaesthetized cats and pigs, Org 9426 was approximately 20% as potent as vecuronium, its onset of action was twice as rapid as that of vecuronium in the cat and its duration of action was similar to that of vecuronium in both cats and pigs. It blocked the bradycardia produced by vagal stimulation only in doses greater than those necessary to produce neuromuscular block (ratios 7.2 in the cat and 4.4 in the pig—10—14% of the corresponding ratios for vecuronium). Ganglion block was seen only at doses several times those producing vagal block. In general the effects of Org 9426 on the cardiovascular system were slight, a small depressor effect occurring at high doses in the cat. The 17-hydroxy analogue, the potential metabolite of Org 9426, was approximately 20 times less potent than Org 9426 and is thus unlikely to contribute to the neuromuscular block produced by the parent compound.


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