STUDIES ON THE INTER-RELATIONSHIP OF CERTAIN CHOLINERGIC COMPOUNDS V. THE SIGNIFICANCE OF THE ACTIONS OF THE 3-HYDROXY PHENYLTRIMETHYL- AMMONIUM ION ON NEUROMUSCULAR FUNCTION’

It has been long accepted that the anti-curare action of neostigmine is at-tributable to its strong inhibitory effect on cholinesterase. The recent demon-stration of the direct stimulatory action of neostigmine on the neuromuscular junction (Riker and Wescoe, 1946) however, suggested that the anti-curare effect of neostigmine might not be due entirely to anticholinesterase action. Moreover, the possibility existed that the direct action of neostigmine was the predominant force involved in its antagonism to curare. This possibility was sub-stantiated by results obtained in an investigation of the acetyl ester of 3-hy-droxy phenyltrimethylammonium methylsulfate (Nu 2017) (Riker et al., 1949; Wescoe et al., 1949). In this compound anticholinesterase action was largely lacking (Wescoe et al., 1950) but prominent effects on neuromuscular function remained. The pharmacologic properties of Nu 2017 were characterized by a direct excitatory action at the neuromuscular junction and a potent anti-curare effect, unaccompanied by significant muscarinic stimulation. It was evident, therefore, that the loss of the carbamate moiety, responsible for a specific anti