Dr. A. D. Waller and Miss S. C. M. Sowton. [June 12, 



"The Action of Choline, Neurine, Muscarine, and Betai'ne on 

 Isolated Nerve and upon the Excised Heart." By A. D. 

 WALLER, M.D., F.R.S., and S. C. M. SOWTON. Eeceived 

 June 12, Eead June 18, 1903. 



In 'connection with the identification by Halliburton and Mott of 

 choline in morbid cerebro-spinal fluid, we compared the action upon 

 isolated nerve and upon the excised heart of the four closely related 

 organic bases: choline, CsHisNO^; neurine, CoHi 3 NO; muscarine, 

 CoHiaNO? ; and betaine, C 5 Hi 3 N0 3 ; we have also, thanks to the kind- 

 ness of Professor Wright and of Mr. Plimmer, taken occasion to examine 

 in a similar manner certain pathogenic toxines, viz. : snake venom 

 (Calmette), diphtheria toxin, and tetano-toxin. 



According to previous investigators, muscarine is powerfully toxic, 

 arresting the heart in diastole (Schmiedeberg) ; neurine has an action 

 resembling that of muscarine ; choline (which formerly was not dis- 

 tinguished from neurine) has a less powerful action than that 

 of neurine, and betaine is considered to be an inert substance. 

 (With regard to their possible action upon nerve, there are, so far 

 as we know, no definite observations.) The direct action of muscarine 

 upon nerve was incidentally examined by one of us in a general 

 survey of the action upon nerve of a series of vegetable alkaloids; 

 that of choline and neurine was examined in comparison with a cerebro- 

 spinal residue and briefly reported upon at the Cambridge Congress of 

 Physiology (1897). 



At that time, confining ourselves to a procedure in which the 

 nerve was submitted to observation for a period not exceeding one 

 hour, interrupted by a period of immersion of one minute duration, 

 we found that muscarine was to be ranked with alkaloids possessing 

 "little or no action " upon nerve, with, however, the express reserva- 

 tion that " such a statement must not be taken as committing us to a 

 denial of any action whatever by the drug acting in stronger solution 

 or for a longer period." 



And in point of fact, muscarine which, under the conditions 

 systematically observed by us at the outset of these observations, is 

 to be classified as inactive, is manifestly active (a) in stronger solution 

 for the same short period of immersion, and (b) in the same weak 

 solution for a longer period of immersion. The former of these two 

 statements is illustrated by fig. 1 (3319), giving the effect of muscarine 

 nitrate in 10-per cent, solution acting for one minute ; the latter 

 statement by e.g., fig. 4 (vide infra), which represents the course of an 

 observation extending over 60 hours, in which two nerves were three 

 times submitted to prolonged immersion in a 1-per cent, solution of 

 muscarine hydrochloride. 



