PHARMACOLOGICAL ACTION OF TETR A- ALKYL- AMMONIUM COMPOUNDS. 499 



Owing to the contracture induced, the extent of the contractions is less than 

 normal, but the contractions plus the contracture have always equalled and 

 sometimes exceeded at first the height of the normal contractions. About two 

 minutes after immersion the contractions begin to diminish, and three to four 

 minutes later the nerve-endings are paralysed. With concentrations down to 

 one-tenth isotonic (0T2 per cent.) the nerve-endings are paralysed in about the 

 same time. With still smaller concentrations the time required for paralysis to 

 occur gradually increases. 



Boehm # found that rhythmic stimulation of the muscle directly or indirectly 

 shortened the duration of the contracture, and his statement I have corroborated 

 for tetra-methyl-ammonium chloride. But it has not occurred to a marked extent 

 in all cases, especially in those in which indirect stimulation was used alone, and 

 in my experiments it has occurred more readily with isotonic solutions than with 

 weaker solutions (cf. figs. 10 and 11). The effect of an isotonic solution of tetra- 

 methyl-ammonium chloride on the two gastrocnemii of a frog, one of which was 

 stimulated alternately directly and indirectly, is seen in fig. 10. The upper portion 

 of the tracing shows the effect produced on the unstimulated muscle, and the lower 

 portion the effect on the muscle stimulated directly and indirectly every ten seconds, 

 with an omission every minute. In the latter case the base line was reached two 

 minutes after the tetra-methyl-ammonium chloride solution was applied, with the 

 unstimulated muscle the base line was not reached until twenty minutes had elapsed. 

 The tendency of the stimulations to cause inhibition of the contracture is often seen 

 in a slight rise of the curve immediately after the stimulation. This may be noticed 

 in fig. 10, and to a greater degree in the curve obtained with di-methyl-di-ethyl- 

 ammonium chloride shown in fig. 15. A muscle which has not been stimulated 

 electrically generally shows a considerable irritability to powerful stimuli directly 

 applied after a muscle which has been rhythmically stimulated has completely 

 lost its irritability. To indirect stimulation, however, no decided difference was 

 obtained. 



Continuous stimulation of a nerve for a considerable time did not appear to 

 affect very materially the contracture of the muscle when subsequently immersed in 

 0'4 per cent, tetra-methyl-ammonium chloride solution. For example, the sciatic 

 nerve of a sciatic-gastrocnemius preparation, the muscle of which was immersed in 

 Ringer's solution, and which contracted well when the nerve was stimulated with a 

 break shock with the secondary coil at 48 cm., was stimulated for twenty-four 

 minutes with the secondary coil at 12 cm., then for three minutes with the secondary 

 coil at 6 cm., and afterwards for one minute with the coil full up. The termination 

 of this stimulation is shown at the commencement of fig. 12. The stimulation was 

 discontinued for ten seconds and then repeated for thirty seconds, after which it 

 was stopped and isotonic tetra-methyl-ammonium chloride solution applied two 



* Loc. cit. 



