PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 495 



solutions of the two substances of equal electrical conductivity show no alteration of 

 conductivity when mixed ; and a mixture of the two compounds when applied to 

 muscle produce a well-marked although more transient contracture than a solution 

 without calcium. This is seen in fig. 6, the lower portion of which shows the 

 contracture obtained with a mixture of isotonic calcium chloride one part, isotonic 

 tetra-methyl-ammonium chloride one part, 0'65 per cent, sodium chloride three parts ; 

 and the upper portion, the curve obtained from the sartorius of the opposite side with 

 a mixture of isotonic tetra-methyl-ammonium chloride one part and 0'65 per cent, 

 sodium chloride four parts. The apparent antagonism of these large concentrations 

 of calcium chloride is chiefly due to their depressant action on the irritability of the 

 muscle-tissue. This can readily be followed by steeping the muscle first in normal 

 saline and applying the calcium chloride subsequently. In such experiments the 

 effect of a fourth isotonic solution of tetra-methyl-ammonium chloride at any time 

 will be found to be comparable with the irritability of the muscle to electrical 

 stimulation. In one experiment in which the effect was followed, the right sartorius 

 was immersed in a mixture of equal parts of isotonic calcium chloride and 0'6 per 

 cent, sodium chloride for seventeen minutes, and then in 0'6 per cent, sodium chloride 

 for ten minutes. A fair degree of irritability of the muscle was then present, and 

 the application of 0'2 per cent, of tetra-methyl-ammonium chloride in isotonic 

 solution produced a corresponding degree of contracture. The left sartorius was 

 allowed to remain in 0"6 per cent, sodium chloride solution for two hours, and then 

 in equal parts of isotonic calcium chloride solution and 0"6 per cent, sodium chloride 

 for ten minutes, at which time a very slight contraction to a faradic stimulus 

 (secondary coil at 8 cm.) was obtained, and a scarcely appreciable contracture on 

 applying 0*2 per cent, tetra-methyl-ammonium chloride. This effect of the calcium 

 ion in diminishing the irritability is probably the explanation of the less sustained 

 curve seen in fig. 6. 



But besides diminishing the irritability of the muscle, calcium chloride also seems 

 to diminish the rate of absorption of tetra-methyl-ammonium chloride into the 

 muscle. This at least appears to be one of the causal factors of the markedly 

 prolonged contracture produced in the gastrocnemius by solutions of tetra-methyl- 

 ammonium chloride after the previous application of a solution of calcium chloride 

 (fig. 7). There is probably also a certain degree of physiological synergism in the 

 action of these two substances, but the question has not been sufficiently investigated, 

 to prove it beyond doubt. 



When the excised sartorius is stimulated by a faradic current (break shock), sent 

 through its length at regular intervals, it is found that the relaxation following the 

 contracture produced by tetra-methyl-ammonium chloride is accompanied by 

 diminished irritability of the muscle. From this depression the muscle gradually 

 recovers, and the contractions, notwithstanding the continued action of the tetra- 

 methyl-ammonium chloride, become as powerful or even more powerful than before 



