0\ THE ANTAGONISM BETWEEN ACTIVE SUBSTANCES. 127 



he administered whereby the uon-antagouized actions will be produced in 

 Bufflcient degrees of energy to be able to cause death. It was probable, 

 therefore, that successful antagonism would not be exerted throughout an un- 

 limited range of doses, but only within a definite range. 



In order to define the limits of the counteracting influence of atropia upon 

 the lethal action of physostigma, three series of experiments were made. 



It was found necessary to make all the experiments of these three series 

 on rabbits, as it was impossible to obtain a sufficient number of any other 

 suitable animal. The rabbits used were generally about three pounds in 

 weight ; but when they were lighter or heavier than three pounds a correction 

 was made, so that each dose represented three pounds weight of animal. 



In the first and second series a constant interval of time was maintained 

 between the administration of the two substances ; but in the first atropia 

 was administered five minutes before physostigma, while in the second atropia 

 was administered five minutes after physostigma. In both of these series 

 experiments were made, in the first place, with the minimum lethal dose of 

 physostigma, and in combination with it various doses of atropia were given, 

 ranging from one that was too small to prevent death, through a number that 

 were able to do so, until a dose was found whose administration resulted in 

 death. Similar experiments were made with a dose of physostigma once and 

 a half as large as the minimum lethal ; then with one twice as large as the 

 minimum lethal, and so on, at the same rate of progression, until a dose was 

 reached that was too large to be successfully counteracted by any dose of 

 atropia. 



The results obtained by the first of these two series of experiments were, 

 that with the minimum lethal dose of physostigma 0-005 gr. of sulphate of 

 atropia is too small a dose to prevent death, but that 0015 gr. is sufficient 

 to do so; and that with any dose ranging from 0-015 gr. to 5-2 grs., the 

 fatal effect of this dose of physostigma may be prevented ; while if the dose 

 of sulphate of atropia be 5-3 grs. or more, the region of successful antagonism 

 is left, and death occurs. With once and a half the minimum lethal dose 

 of physostigma, successful antagonism was produced by doses of sulphate 

 of atropia ranging from 0-02 to 4-1 grs. ; with twice the minimum lethal 

 dose of physostigma, with doses of sulphate of atropia ranging from 0-021 to 

 3-2 grs. ; with two and a half times the minimum lethal dose of physostigma, 

 with doses of sulphate of atropia ranging from 0-025 to 2-2 grs. ; with thrice 

 the minimum lethal dose of physostigma, with doses of sulphate of atropia 

 ranging from 0-06 to 1-2 gr. ; and with three and a Jialf times the minimum 

 lethal dose of physostigma, with doses of sulphate of atropia ranging from 

 0-1 to 2 gr. Successful antagonism could not be obtained above this dose, 

 and accordingly three and a half times the minimum lethal dose of physo- 

 stigma is the largest quantity wtose lethal action can be prevented by 

 atropia administered five minutes previously. 



The results obtained by the second series of experiments (in which atropia 

 was administered five minutes after physostigma) were essentially the same as 

 those obtfined by the first series, excepting that the region of successful 

 antagonism was found to be a more limited one. In both series the general 

 result was obtained, that the range of doses of atropia capable of preventing 

 the lethal action of physostigma diminishes according as the dose of physo- 

 stigma is increased. 



In the third series of experiments, a constant dose of physostigma (once 

 and a half the minimum lethal) was given along with various doses of 

 atropia ; and with each of the doses of atropia several experiments were 



