380 PROFESSOR C. R. MARSHALL ON THE 



there were some loss of co-ordination, a varying degree of paralysis with diminution 

 or absence of reflexes, and diminution or cessation of the respiratory movements. 

 Winter frogs kept in the laboratory were less sensitive to this substance than 

 recently caught summer frogs. 



The muscular contractions and tremors appeared in the case of summer frogs 

 within three minutes of the injection of a large dose (2 mg. per gramme weight of 

 frog), in five to eight minutes after a moderate dose (0*5 mg. per gramme weight of 

 frog), and in twenty to thirty minutes after a minimal effective dose (0'05 mg. per 

 gramme weight of frog). Most commonly they seemed to commence in the dorsal 

 or abdominal muscles, but in some animals the muscles of the limbs were first 

 influenced. Sometimes, and especially after large doses, the tremors and contractions 

 were general from the outset. In all cases the irregularity in distribution and extent 

 of the movements was marked. 



At first the contractions were usually fibrillary and shortly tonic in character. 

 Later, large muscle-bundles or even whole muscles were involved, producing in the 

 case of the limbs somewhat grotesque movements. Still later, if the dose administered 

 were sufficient, they assumed the form of twitches, which became less frequent and 

 finally ceased. In some cases they persisted for hours, and often continued after the 

 cessation of all reflex activity. The movements of the hind-limb muscles were the 

 last to disappear. Except after large doses, they were not constantly present during 

 the earlier stages of the intoxication. Intervals of several minutes often occurred 

 between successive twitches, and frequently they were induced by a voluntary 

 movement. Such a movement generally intensified them if present. 



After doses larger than 0'3 mg. per gramme body-weight the stage of irregular 

 muscular contractions usually passed into one of complete paralysis, which lasted a 

 variable time. After the injection of 1 mg. per gramme of frog, paralysis occurred 

 in fifteen minutes and complete recovery within eighteen hours. After double this 

 dose, paralysis developed in five minutes and recovery did not occur. The muscles 

 associated with respiration were the first to be paralysed and, if a non-lethal dose 

 had been given, were the first to recover. After doses less than 0'3 mg. per gramme 

 frog, complete paralysis did not follow, but more or less muscular weakness was 

 noticeable. 



Tillie* states that doses of 0*01 g. to 0'02 g. induce in frogs powerful general 

 fibrillary contractions before the onset of paralysis, but no mention is made of the 

 occurrence of tremors by Santesson and KoRAEN.t They were, however, observed 

 by Brunton and Cash \ and by Jacobj and Hagenberg § after the administration of 

 the iodide. But Brunton and Cash || describe the symptoms produced by 0'007 g. 

 to 0'028 g. of tetra-ethyl-ammonium iodide as being the same as those produced by 

 similar doses of tetra-methyl-ammonium iodide. These were " spasmodic twitchings 

 of trunk and limb muscles ; limbs drawn up in a very tremulous manner ; whole 



* Loc. cit. t Loc. cit. j Loc. cit., p. 205. t" Loc. cit., p. 58. || Loc. cit., p. 205. 



