PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 491 



foundly in intensity. The fall of blood-pressure and the depressant effect on the circu- 

 lation do not run a parallel course, and the two effects are largely independent. 



Effect on Isolated Muscle of Frog. 



The effect of these quaternary compounds on the isolated frog's muscle presents 

 some features of interest which bear upon the mode of action of these substances. 

 The experiments were made on the sartorius and gastrocnemius at rest and during 

 periodic stimulation with a break faradic current. The apparatus used to record 

 the effect on unstimulated muscles consisted of a small rectangular glass vessel with 

 holes bored at the ends, through which were fitted corks carrying a small hook and 

 a piece of fine thermometer tubing respectively. The hook transfixed the patellar 

 tendon, and a silk thread — fastened through the acetabulum in the case of the 

 sartorius preparation, and through the tendo Achillis in the case of the gastro- 

 cnemius — passed along the bore of the thermometer tubing and over a pulley in 

 line with it to a writing-lever which recorded the movements. The writing-lever 

 magnified the contractions five times. The sartorius in most experiments was 

 weighted with half to one gramme, the gastrocnemius with five grammes. When 

 the muscle was stimulated with a break faradic current through its length, Wild's 

 apparatus # was used and the movements were magnified nine times. The solu- 

 tions employed were isotonic or of equal electrical conductivity, with 0'6 per cent, 

 sodium chloride. 



When the sartorius or gastrocnemius muscle of a frog is steeped in 0'6 per cent, 

 sodium chloride solution or in Ringer's fluid for some time and then subjected to a 

 similar isotonic solution containing O'l per cent, tetra-methyl-ammonium chloride, 

 immediate contracture, as described by BoEHM,t is produced. The extent of the 

 contraction is greater with the sartorius than with the gastrocnemius, apparently 

 owing, in the main, to its greater length and the more longitudinal arrangement 

 of its fibres. The contracture is followed by a somewhat rapid and complete 

 relaxation in the case of the sartorius, and by a much more gradual, sometimes 

 incomplete, relaxation in the case of the gastrocnemius. 



A similar contracture occurs when the muscles are immersed in solutions of 

 tri-methyl-ethyl-ammonium chloride, a fact also mentioned by Boehm.} The effect 

 is less powerful than that obtained with equimolecular solutions of tetra-methyl- 

 ammonium chloride, and greater concentrations are needed to produce a minimal 

 effect. The limit concentration producing an appreciable contracture in my 

 experiments with the sartorius muscle was, for tetra-methyl-ammonium chloride, 

 O'OOOOl per cent. ; for tri-methyl-ethyl-ammonium chloride, 0'00005 per cent. 



This contracture is not obtained from the sartorius with any strength of solution 

 up to slightly hypertonic of any other members of the series. If, however, an 



* Brit. Med. Journ., 1887, ii. p. 500. t Arch. f. exp. Path. u. Pharmak., lviii. p. 267 [1908]. 



X Loc. cit. 



