Interaction at end-plate receptors between different choline derivatives

Interaction between different choline derivatives has been studied by applying them simultaneously to a motor end-plate and recording the resulting changes in the membrane potential of the muscle fibre. Choline potentiates the depolarizing effect of acetylcholine (Ach) when applied in normal Ringer. Decamethonium has a 'diphasic' action, initial depression of the Ach effect being followed by more prolonged potentiation. When these experiments are made after treating the muscle with an esterase inhibitor (prostigmine $10^{-6}$ $\text{w/v})$, the potentiation of the Ach effect, by decamethonium or choline, is absent and replaced by simple 'curare-like' inhibition. When decamethonium is allowed to interact with a rapidly acting stable ester (carbaminoly-choline or succinylcholine), it produces simple 'curare-like' inhibition. The triple effects of choline and decamethonium, i.e. (i) weak depolarization, (ii) potentiation of Ach in normal Ringer solution, (iii) inhibition of Ach in the presence of prostigmine, can be explained by competitive reactions between the drugs and receptor as well as Ach-esterase molecules. It is suggested that the first step in a depolarizing end-plate reaction is the formation of an intermediate, inactive, compound between drug and receptor.