The curariform action of quaternary ammonium salts

Abstract

The original observation of Crum Brown and Fraser (1869) that metho-salts derived from certain alkaloids did not show the physiological activities typical of their parent bases, but possessed, in common with the simplest quaternary ammonium salt, viz., tetramethylammonium chloride, the property of a curari-like action upon striated muscle, provided one of the earliest examples of uniformity of physiological action among the members of one chemical class. The true curariform nature of the action of quaternary ammonium salts was later confirmed by Rabateau (1873), Brunton and Cash (1884) and other workers. At relatively high concentrations quaternary ammonium salts depress the excitablility of muscle to direct stimulation, as was shown by Boehm (1910) and Hober and Waldernberg (1909) for tetramethylammonium and also diminish the conductivity of the nerve (Jodlbaur, 1900), but paralysis to indirect stimulation is produced by these salts at concentrations well below that required to affect either the nerve or the muscle. Since the original observation of Crum Brown and Fraser, a great variety of quaternary ammonium salts has been shown to posses the curariform action, but few attempts have been made to compare the behaviour of these salts quantitatively under comparable conditions. Kulz (1922) attempted to estimate the minimum concentrations of alkyltrimethyl- and alkyltriethyl- ammonium salts required completely to paralyse the isolated frog's sciatic-gastrocnemius, but he neglected the time factor involved and consequently his results are without quantitative significance. In the alkyltrimethyl series the propyltrimethyl compound was the least active and the higher members of the series up to octyltrimethyl had about the same activity as the tetramethyl compound. The lower members of the alkyltriethyl series were less active than their alkyltrimathyl analogues, but the higher members of both series had approximately the same activity.