A comparison of the neuromuscular blocking and autonomic effects of two new short-acting muscle relaxants with those of succinylcholine in the anesthetized cat and pig.

The actions of two new steroidal nondepolarizing neuromuscular blocking agents, structurally related to vecuronium, have been compared with those of succinylcholine in anesthetized cats and pigs. Both new compounds (Org 7617 and Org 9616) exhibited properties typical of nondepolarizing relaxants in each species. Org 9616 was one-fifth (ED50 cat tibialis 154 micrograms.kg-1) and Org 7617 was one-tenth (ED50 cat tibialis 287 micrograms.kg-1) as potent as vecuronium as a neuromuscular blocking drug. Both compounds produced rapidly developing muscle relaxation in cats that, like that of succinylcholine, was transient in time course (onset/duration of action--tibialis anterior muscle: Org 7617 1.6/3.9 min; Org 9616 1.5/4.3 min; succinylcholine 1.7/5.7 min). In pigs that were used as a predictor of duration of action in humans, both Org 7617 and Org 9616 also produced short-lived neuromuscular blockade. The neuromuscular blocks produced by Org 7617 and Org 9616 were readily reversed by neostigmine. Both compounds blocked the heart rate responses to vagal stimulation at doses higher than those required to produce neuromuscular block. The vagal:neuromuscular blocking ratio for Org 7617 was 10, and for Org 9616 was 17. These compare to approximate published values for vecuronium, atracurium, and pancuronium of 60, 25, and 3, respectively. Ganglion block was only seen at 30-60 times the neuromuscular blocking doses. Both compounds produced a decrease in arterial blood pressure. This was more pronounced with Org 7617. In addition, Org 9616 produced a slight increase in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)