A comparison between the effects of edrophonium and choline in the skeletal muscles of the cat

Abstract

The effects of edrophonium and choline have been compared with those of the depolarizing substances acetylcholine, decamethonium, and suxamethonium, in both innervated and chronically denervated tibialis anterior muscles of cats under chloralose anaesthesia. Both edrophonium and choline were more potent antagonists to paralysis by tubocurarine than could be accounted for by their ability to stimulate the motor end-plates directly. It appeared likely that direct depolarization of the end-plate played no part in the anti-curare action of edrophonium and only some part in the anti-curare action of choline. A paralysis produced by the neuromuscular blocking agent, benzoquinonium, was more readily antagonized by a tetanus or by acetylcholine, suxamethonium, and decamethonium than a similar paralysis produced by tubocurarine. The tetraethyl ammonium ion was also slightly more effective against a paralysis by benzoquinonium. On the other hand, edrophonium was about 300 times and choline about five times less potent as an antagonist to benzoquinonium than to tubocurarine. Furthermore, the previous administration of benzoquinonium abolished the antagonistic action to tubocurarine of normally effective doses of edrophonium and reduced that of choline. These results were similar to those previously obtained with neostigmine, physostigmine and ethyl pyrophosphate and suggested that there was some similarity in the mechanism of action of all of these substances. Benzoquinonium, therefore, showed promise as a useful pharmacological tool for distinguishing compounds with this particular type of action. These anti-curare compounds did not appear to act by cholinesterase inhibition, not by an increase in the sensitivity of the motor end-plates. In common with other workers, we suggest that there is a pre-synaptic mechanism of action.