602 DR THOMAS R. FRASER ON THE ANTAGONISM BETWEEN 



of atropia succeeds that of physostigma by ten minutes, than when it succeeds 

 it by only five minutes. This difference is one, certainly, which I did not 

 anticipate. My expectation was rather that the maximum successfully 

 antagonising dose of sulphate of atropia would be greater when the interval 

 was one of five minutes, than when it was one of ten minutes. It is difficult 

 to account for the result that has been obtained. I cannot attribute it to any 

 known cause of fallacy in the circumstances of the experiments ; and the expla- 

 nation that it is simply due to some of the causes of fallacy that are unavoidable 

 in such a research, seems to be opposed by its being derived, not from one or 

 two experiments only, but from seven, of which four belong to the interval of 

 five minutes, and three to that of ten minutes. Of the experiments belonging 

 to the former interval, death occurred in one where the dose of sulphate of 

 atropia was 2 3 grains, in two where it was 2*4 grains, and in one where it was 

 2 - 5 grains ; while of the experiments belonging to the latter interval, recovery 

 occurred in one with each of these doses. Further, of these experiments, two 

 differing in the interval but agreeing in the dose of sulphate of atropia (2*4 

 grains) were performed on the same day, on rabbits of nearly the same weight, 

 and as far as could be judged, of equally healthy condition, and yet, as has 

 already been stated, death occurred in the experiment with the former interval 

 (Experiment 202), and recovery in that with the latter interval (Experiment 

 268-a). 



Still, notwithstanding these various circumstances, it may be that the result 

 is due to a mere accident. If, however, it be not so, its occurrence may possibly 

 be explained by supposing that the non-antagonised action or actions of 

 physostigma produce their maximum effect after a greater interval of time 

 from the administration than is the case with atropia. If this be assumed, it 

 is obvious that death will be most easily produced when the administration 

 of the two substances is so timed that the two maxima of effect may coincide. 

 These various suppositions being granted, the apparently anomalous result 

 of a larger dose of sulphate of atropia being within the range of successful 

 antagonism when the interval is one of ten minutes than when it is one of five 

 minutes, may be accounted for, by assuming that certain actions produced by 

 the two substances are not present in so great a degree of combined intensity 

 when atropia is given ten minutes after physostigma as when it is given only 

 five minutes after it. 



Passing now to the experiments in which the interval of time was greater 

 than ten minutes, I find that only one experiment was made in which atropia 

 was administered fourteen minutes after physostigma (Experiment 272-<z). In 

 this experiment, the dose of sulphate of atropia was three tenths of a grain, 

 and with it the fatal effect of one and a half times the minimum-lethal dose of 

 physostigma was successfully antagonised. 



