A comparison of the neuromuscular blocking and vagolytic effects of ORG NC45 and pancuronium

ORG NC45, a neuromuscular blocking agent not producing tachycardia, was examined first, to establish the kinetics of the anatagonism it produces, and second, to test the hypothesis that the tachycardia seen with pancuronium and gallamine reflects an action on vagal postganglionic nerve endings. The action of ORG NC45 was studied on end-plate depolarization and neuromuscular transmission in the guinea pig lumbrical muscle. Also, the effect of ORG NC45 on the response of the cardiac pacemaker to carbachol and on the response of the pacemaker to pre- and postganglionic vagal stimulation was examined in isolated guinea pig atria. ORG NC45 was a potent neuromuscular blocking agent (twice as potent as pancuronium) in this species and showed typical competitive kinetics with a dissociation constant of 0.0103 micro M. However, ORG NC45 affected the atrial system only at very high concentrations and did not affect release of transmitter from vagal nerve terminals. These results thus confirm the hypothesis that presence or absence of vagolytic action goes hand-in-hand with tachycardia or its absence clinically.