Some actions of Org NC 45 and of edrophonium in the anaesthetized cat and in man.

Some actions of the muscle relaxant drug Org NC 45 on the tibialis anterior muscle of cats under barbiturate-chloralose anaesthesia have been studied. Its effects were characteristic of a neuromuscular blocking agent that acts predominantly, although not necessarily exclusively, by blocking postjunctional cholinoceptors. It was confirmed that one of the important features of the action of Org NC 45 is that, despite its high potency, its offset of action is unusually rapid. The pronounced antagonism of the block following an interposed tetanus suggested that Org NC 45 is more easily displaced from the endplate cholinoceptors than are tubocurarine or pancuronium, and this led to the idea, confirmed by experiment, that edrophonium would be a more effective antagonist of Org NC 45 than of most other neuromuscular blocking drugs. Edrophonium was about 12 times less potent than neostigmine in antagonizing Org NC 45. However, with equipotent antagonistic doses, edrophonium restored transmission to control (as measured by the train-of-four test) at least twice as rapidly as neostigmine and, more importantly, edrophonium had a much weaker effect than neostigmine on the cardiac vagus. The results obtained in cats with edrophonium were essentially confirmed in preliminary studies on nine anaesthesized patients. In these studies, a dose of edrophonium 0.5 mg kg-1 i.v. was found to produce adequate and rapid antagonism of Org NC 45, and because of the relatively weak side-effects of edrophonium, it was necessary, about 30 s before edrophonium, to administer only 0.6 mg of atropine (about 9 micrograms kg-1), which is half the dose commonly used when neostigmine is the reversal agent. These preliminary observations in man suggest that edrophonium may be the reversal agent of choice for Org NC 45.