PHARMACOLOGICAL ACTION OF TETRA-ALKYL- AMMONIUM COMPOUNDS. 383 



of the injection. The heart-beats were apparently normal at this time, but later 

 they became weaker and less frequent, and finally ceased seven minutes after the 

 end of the injection. Two minutes previously a few tremors of the right fore limb 

 were noticed. 



After the intravenous injection of 0'25 g. per kg. body- weight, death occurred 

 within a minute of the termination of the injection. A few slight convulsive move- 

 ments, chiefly of the hind limbs, occurred during the injection, but the breathing 

 had ceased and the fore part of the body was completely, and the hinder part almost 

 completely, paralysed at the end of the injection. The heart-beats were then feeble ; 

 they ceased before another minute had passed. The pupils were markedly contracted. 

 Tremors of the back muscles occurred soon after the cessation of the injection, and 

 somewhat later tremors of the abdominal muscles. Half an hour after death tremors 

 in the hind limbs were present. 



Effect on Nerves and Muscles. 



Both the muscular contractions and the paralysis observed in frogs are peripheral 

 in origin. They are obtained as easily in frogs in which the brain and spinal cord 

 have been pithed as in normal animals, and are readily obtained by the local applica- 

 tion of the substance to exposed muscles. 



Santesson and Koraen # state that they found it difficult to determine the 

 paralysing action of tetra-ethyl-ammonium chloride on the nerve-endings owing to 

 its action on the muscle-substance. This difficulty has not presented itself in my 

 experiments. In all, whether on intact frogs or on muscle-nerve preparations, the 

 myo-neural junction was found to be paralysed at a time when the irritability of the 

 muscle was little affected. In a frog which had received 1*5 mg. per gramme body- 

 weight into the dorsal lymph-sac, and which, after the development of preliminary 

 tremors, was completely paralysed in ten minutes, the muscles when tested twenty 

 hours later were found to react with the secondary coil (the primary current being 

 obtained from one accumulator cell) at 19 cm., while the sciatic nerves did not 

 react with the coil full up. In a second experiment, in which the frog received 2 mg. 

 per gramme body-weight and was pithed one and three-quarter hours after the 

 injection, the gastrocnemii muscles reacted with the secondary coil at 40 cm., the 

 sciatic nerves being unirritable with the strongest current. With smaller doses the 

 same phenomena but in less degree were observed. After the injection of 0'4 mg. 

 per gramme of frog and pithing three hours later, the gastrocnemii reacted with the 

 secondary coil at 36 cm., the right sciatic was irritable with the coil at 8 "5 cm., and 

 the left sciatic with the coil at 4'5 cm. 



By means of a Claude Bernard experiment the predominant influence of tetra- 

 ethyl-ammonium chloride on the nerve-endings is more decidedly shown. Thus, in a 

 frog with the brain pithed and with the left iliac artery and vein ligatured and 



* hoc. cit., p. 225. 



