508 



PROFESSOR 0. R. MARSHALL ON THE 



for some time longer still reacting well to direct stimulation. An injection of 



O'Ol g. into the dorsal lymph-sac of a frog (weight 13 g.) with the brain pithed 



and the left thigh, excluding the sciatic nerve, doubly ligatured, gave the following 



results when the sciatic nerve and the gastrocnemius muscles were tested two and a 



half hours later : — 



Right sciatic nerve . Slight twitch with tetanic stimulation, secondary coil at 20 cm. No 



tetanus with coil full up. Reflex movements in other (pro- 

 tected) limb. 

 Slight tetanus with coil at 36 cm. 

 Twitch with coil at 32 cm. 

 Twitch with coil at 32 cm. 



This substance therefore paralyses the motor nerve-endings before the muscle, and 

 since metho-chlorides have a similar action to the corresponding meth-iodides, it 

 would seem probable that papaverine metho-chloride possesses a paralysing action 



Left sciatic nerve . 



Right gastrocnemius muscle 



Left gastrocnemius muscle 





Fig. 23. — Effect of - 3 per cent, papaverine meth-iodide on irritability of gastrocnemius of frog. Description as for fig. 14. 



on motor nerve-endings and that these papaverine derivatives are not exceptions to 

 the rule that quaternary compounds paralyse the myo-neural junction. It seems to 

 me that no authentic instance of a pharmacologically active quaternary compound * 

 which does not affect the myo-neural junction has, as yet, been found. t These 

 compounds vary considerably in activity, and they may produce other effects than 

 paralysis of peripheral origin, but even when such actions are present the peripheral 

 paralysis is an important if not a predominant effect. 



The variability in action of quaternary compounds is well shown in the case of 

 tetra-methyl-ammonium chloride and tetra-ethyl-ammonium chloride, and there can 

 be little doubt that a solution of the cause of this difference would materially help to 

 solve the problem of the mode of action of this class of substances. There appears, 

 however, to be no sufficient differences in the known chemical and physical properties 



* Certain quaternary compounds, such as the betaiues, which contain a carboxyl or lactonic group, are 

 pharmacologically inert, and do not therefore affect nerve-endings. 



t Fraenkel (Die Arzneimittel-synthese, 2 te Aufl. p. 301) refers to a research by Ihmsen, who found methyl-ethyl- 

 coniine hydroxide inactive in doses of 30 g., and the iodide in doses of 6 g., although the latter substance in doses of 

 10 g. produced death in four minutes. No details are given, and Ihmsen's paper is unknown to me. It may be 

 remarked that methyl-coniine and di-methyl-coniine compounds (Crum Brown and Fraser, loc. cit.), and ethyl- 

 coniine hydroxide (Tiryakian, Paris thesis, 1878, quoted by Fraenkel), have been shown to paralyse motor 

 nerve-endings. 



