Pharmacology of Some bis -Trimethyl Ammonium Compounds

THE curare-like action of a series of bis-quaternary ammonium polymethylenes has recently been described by Barlow and Ing1 and by Paton and Zaimis1, and we can confirm that the C3 compound curarizes, but is relatively inactive compared with d-tubocurarine chloride on the rat diaphragm (1 per cent). Its action was completely reversed by prostigmine. (Tetramethyl ammonium chloride showed about 2·5 per cent of the activity of d-tubocurarine chloride on the rat diaphragm.) The C5 compound had no action on the rat diaphragm. The C3 compound has marked cholinergic action-salivation, lachrymation, bradycardia in decerebrated guinea pig-together with relaxation of decerebrate rigidity at a dose of 1·0 mgm. per kgm. It produced a response of the rabbit's ileum similar to that of acetyl choline (potency about 0·1 per cent that of acetyl choline). It has slight activity as an anticholinesterase (rat brain). It has no action on pseudo-cholinesterase (horse serum). Its cholinergic activity, apart from its low curarizing activity, would clearly render it unsuitable as a clinical substitute for d-tubocurarine. The C5 compound has about the same anticholinesterase activity as the C3.