Pharmacology of various aminosteroidal muscle relaxants

: A large number of analogues of pancuronium and vecuronium have been tested for neuromuscular blocking and other actions in anaesthetized cats, dogs, pigs and monkeys in an attempt to find a nondepolarizing substitute for succinylcholine. The results demonstrated an inverse relationship between dose and brevity of action; that is to say that grief duration was found only among compounds of relatively low potency. Two compounds given the code numbers Org 7617 and Org 9616 were found to possess promising properties. Both compounds are 17-butyrate analogues of vecuronium. Org 9616 also has an allyl group, in place of the methyl group, attached to the quaternary nitrogen at position 16. Both compounds have time courses similar to that of succinylcholine. They do not release histamine or produce ganglion block, and they are both considerably less potent than pancuronium in blocking the cardiac vagus. Both may produce a small fall in blood pressure. Electrophysiological analysis shows that neither compound is expected to occlude the receptor-operated ion channels of the motor endplate in concentrations likely to be achieved clinically.