PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 38'/ 



administration of calcium chloride intramuscularly. Calcium chloride in isotonic solu- 

 tion, when injected into the dorsal lymph-sac in doses of 0'4 mg. per gramme of frog, 

 did not, however, prevent tremors being produced by the injection of tetra-ethyl- 

 ammonium chloride into the ventral lymph-sacs one to one and a half hour subse- 

 quently. But in the two experiments made the tremors did not appear as quickly 

 as in an animal not treated with calcium chloride, and they were later in appearing 

 in the animal in which the longer interval was allowed to elapse before the tetra- 

 ethyl-ammonium chloride was given, although in this case a larger dose was 

 administered. The method, however, proved unsuitable for the end in view, probably 

 owing to the relatively slow absorption and relatively rapid excretion of the calcium 

 salt ; and as Fuhner's method of large intramuscular injections did not seem to me 

 free from fault, perfusion of solutions through the vessels was employed. With this 

 method it was found possible, by the previous perfusion of calcium chloride solutions, 

 to prevent the tremors ordinarily produced by tetra-ethyl-ammonium chloride even 

 when relatively large concentrations were employed. Thus, in a pithed frog perfused 

 for ten minutes with 1 in 1000 calcium chloride in Ringer's solution at the rate of 

 1'5 c.c. per minute, and then with this solution containing 1 in 500 tetra-ethyl- 

 ammonium chloride, no tremors or muscular movement followed. If, however, a 

 diluter solution of tetra-ethyl-ammonium chloride in Ringer is first perfused and 

 well-marked tremors set up, the subsequent perfusion of 1 in 1000 calcium chloride 

 may fail to stop them, probably owing to insufficient calcium reaching the muscles, on 

 account of the contracted state of the vessels induced. In this connection it is worthy 

 of mention that when Ringer was used as the normal perfusion fluid the subsequent 

 perfusion of moderately strong solutions of tetra-ethyl-ammonium chloride caused 

 contraction of the vessels; if Ringer's solution containing 1 in 1000 calcium chloride 

 were first perfused, the subsequent perfusion with added tetra-ethyl-ammonium 

 chloride caused dilatation. 



The inhibitory action of the calcium ion on the tremors and contractions produced 

 by tetra-ethyl-ammonium chloride may also be conveniently demonstrated on the 

 excised sartorius muscle of the frog. When this muscle is placed in an isotonic sodium 

 chloride solution (Ringer # ), or better in an isotonic salt solution containing sodium 

 phosphate and a little sodium carbonate (Biedermann t), it shows fine tremulous and 

 vermicular movements which are inhibited by the addition of a small quantity of a 

 calcium salt. This Biedermann phenomenon is noticeably increased by the addition 

 of a little tetra-ethyl-ammonium chloride to the salt solution, and when thus intensi- 

 fied a larger amount of calcium in the solution is necessary to inhibit the movements. 

 Owing to Biedermann's fluid containing an alkaline Carbonate and a relatively large 

 amount of a soluble phosphate, the addition of calcium chloride to it causes precipita- 

 tion of calcium carbonate and phosphate ; hence a simple sodium chloride solution is 



* Journ. of Physiol., vii. p. 295 [1886]. 



t Sitzungsber. d. Kais. Akad. d. Wiss. Wien, lxxxi., III. Abt., p. 257 [1880]. 

 TRANS. ROY. SOC. EDIN., VOL. L. PART II. (NO. 12). 54 



