THE ACTIONS OF PHYSOSTIGMA AND ATROPIA. 611 



founded on the evidence of a sufficiently large number of trustworthy experi- 

 ments to prevent its being regarded as certainly due to some of those unavoid- 

 able variations in the conditions of the experiments that we do not at present 

 know how to make allowance for, although this is the explanation that is most 

 naturally suggested. 



Soon after presenting this anomaly, the line of demarcation between the 

 two regions crosses the line representing simultaneous administration, and 

 then continues its gradual ascent until it reaches the right margin of the 

 diagram. In this course, there are indicated certain points of interest relating 

 to the maximum dose of atropia that produces successful antagonism at different 

 intervals of time. It is seen that this maximum dose is considerably smaller 

 when atropia is administered after physostigma than when the two substances 

 are simultaneously administered ; that is also smaller, though by a less difference 

 than in the previous instance, when the two substances are simultaneously 

 administered, than when atropia is administered five minutes before physo- 

 stigma; and finally, that it augments in size with each increase of the interval 

 of time separating the administration of atropia from the subsequent adminis- 

 tration of physostigma. So that, as I have already pointed out, when such 

 a dose of sulphate of atropia as five grains is used, death occurs when it is 

 administered at any interval after the physostigma, simultaneously with it, or at 

 any interval less than twenty minutes before it; but, on the other hand, recovery 

 generally occurs when it is given at any interval from twenty-five to one hundred 

 and seventy-five minutes before it. 



The portion of the line of demarcation that forms the upper boundary of 

 the region of recovery rises gradually and at a tolerably uniform rate from 

 where it cuts the perpendicular line indicating a twentieth of a grain of sulphate 

 of atropia to where it reaches that indicating five grains ; and as this rise implies 

 a corresponding increase in the interval of time by which the administration of 

 atropia preceded that of physostigma, it displays very clearly another general 

 result of the experiments, namely, the establishment of the fact that the maxi- 

 mum interval of time by which the administration of atropia may compatibly 

 with the production of successful antagonism precede that of physostigma — in 

 other words, the length of time the antidotal influence produced by the adminis- 

 tration of a dose of atropia lasts — gradually and with tolerable regularity 

 increases as the dose of atropia is augmented from one-twentieth of a grain to 

 five grains. How far increase of that interval goes on in the case of further 

 increase of the dose of atropia, has not been tested by experiment ; but it seems 

 likely that were this done, it would be found to stop at a dose of atropia some- 

 where between the largest already tested (five grains) and the minimum-lethal 

 (about twenty-one grains). Near this point, the portion of the line of demarca- 

 tion forming the upper boundary of the region of recovery will reach its highest 



