580 DR THOMAS E. FRASER ON THE ANTAGONISM BETWEEN 



Section B.— DETERMINATION OF THE EXTENT OF THE COUNTERACTING 

 INFLUENCE OF ATROPIA UPON THE LETHAL ACTION OF PHYSOSTIGMA. 



In the " preliminary note " which I communicated to this Society, on the 

 antagonism between physostigma and atropia, the opinion was expressed, that 

 as this antagonism is " concerned with two substances, each of which possesses 

 a number of actions, it is not unreasonable to anticipate that several of them are 

 not mutually antagonistic," and that " above certain doses, a region may, there- 

 fore, be entered where the non-antagonised actions are present in sufficient 

 degrees to be themselves able to produce fatal results." * Besides this con- 

 sideration, there are others derived from our knowledge of the physiological 

 action of physostigma, which render it probable that such a region exists. 



Certain of the actions of the two substances are of a similar nature. When 

 a dose not much above the minimum-lethal of the one is counteracted by a 

 small dose of the other, the similar actions are not produced in sufficient 

 intensity to become, even in combination, important toxic actions. When, 

 however, a dose considerably above the minimum lethal of the one substance 

 is given along with a large dose of the other, the similar actions may be 

 produced in such intensity as to assume the importance of lethal actions. 



Further, with regard to the counteracting actions themselves, it is to be 

 observed that various of the facts mentioned in the record of experiments 

 that is given in the preceding section tend to make mutual antagonism 

 probable, not only of one but of several of the actions of physostigma and 

 atropia ; and it is legitimate to suppose, that with a given dose of physostigma, 

 the counteraction produced by a certain amount of atropia will be more perfect 

 in the case of one or more of the antagonistic actions than in that of others, and 

 that with certain doses of the two substances such incompleteness of counter- 

 action may exist as would, even without the occurrence of wcw-antagonised 

 action, suffice for the production of death. 



Guided by these considerations, I anticipated that the counteracting influence 

 of atropia upon the lethal action of physostigma is successfully exerted only 

 within a definite range of doses, and that this range may be determined by 

 experimental research. The somewhat laborious task of making this deter- 

 mination has been undertaken because it seemed likely that results would 

 thereby be obtained of the greatest interest and novelty, in connection not 

 only with this special instance of counteraction, but also with the general 

 subject of physiological antagonism and its important and direct bearing 

 on the principles of therapeutics. 



* Loc. cit., p. 589. 





