Comparison of the neuromuscular blocking properties of ORG NC 45 and pancuronium in the rat, cat and rhesus monkey.

SUMMARY The neuromuscular and cardiovascular activities of pancuronium were compared with those of its 16β monoquaternary congener, Org NC 45, in the anaesthetized rat, cat and rhesus monkey. In the rat Org NC 45 was 3.4 times less potent as a neuromuscular blocking agent than was pancuronium. In the cat, both drugs were found to be approximately equally eliminated by the liver, whereas renal elimination was observed only with pancuronium. In the rhesus monkey, Org NC 45 was about 1.5 times less potent than pancuronium as a neuromuscular blocking agent. At doses approximately eight times that producing 80%.twitch block, the neuromuscular block produced by Org NC 45 was significantly shorter in duration and recovery than that produced by pancuronium. In addition, these high doses of Org NC 45 did not produce the tachycardia which is seen with pancuronium. Org NC 45 showed less tendency than pancuronium to produce cumulative effects on repeated administration in the monkey. Both Org NC 45 and pancuronium were antagonized by anti-cholinesterases and aminopyridines. It is suggested that the lack of tachycardia with Org NC 45 may be related to the low cardio-selective anti-muscarinic potency of Org NC 45 previously reported in the cat and, together with its low renal elimination and lack of cumulative effects, Org NC 45 may be a clinically useful non-depolarizing muscle relaxant free of cardiovascular side-effects.