THE ACTIONS OF PHYSOSTIGMA AND ATEOPIA. 539 



weighed separately for each experiment, but in several instances it was found 

 necessary to subdivide a recently prepared solution, as such minute doses were 

 required that it would have been impossible to weigh them accurately. 



Subjects of Experiment. — With a few exceptions, wherein dogs were used, 

 the experiments were performed on rabbits. The animals were invariably 

 in a state of perfect health, and in full digestion. The latter is a condition 

 of great importance, the plan of research requiring a strict attention to the 

 relation between the weight of the animal and the doses of the substances. 

 The amount of food contained in the stomach appreciably modifies the weight 

 both of dogs and rabbits, but it does so to a very marked extent in rabbits, for 

 on several occasions I have found that an increase of three or four ounces oc- 

 curred after food had been taken. As, generally, the rabbits employed were 

 about three pounds in weight, the difference represented by such an increase 

 is obviously of importance in estimating the doses of the substances. 



Plan of Experiments. — The following plan was adopted for the experiments, 

 as it appeared to be the one by which the most conclusive results were to be 

 obtained : — In the first place, the minimum fatal dose for rabbits of the extract 

 of physostigma and of the sulphate of physostigmia employed was determined 

 by a number of preliminary experiments, so that, on the weight of the animal 

 being ascertained it was an easy matter to be certain of the dose that could kill 

 it. Then, in those experiments in which recovery followed the administration 

 of a dose of atropia given in combination with a dose of physostigma equal to 

 or in excess of the minimum fatal, the animal used was killed many days after- 

 wards, and when the effects of the two substances had completely disappeared, by 

 a dose of physostigma less than or only equal to that from which it had pre- 

 viously recovered. Therefore, when the administration of atropia prevented an 

 otherwise fatal dose of physostigma from causing death, a perfect demonstration 

 was obtained of the power of atropia to produce some physiological action or actions 

 that counteracted some otherwise lethal action or actions of physostigma. 



The administration of the substances was effected by subcutaneous injection. 

 There is an abundance of evidence to show that, when exhibited by subcutaneous 

 injection, the activity of a substance, relatively to its dose, is considerably greater 

 than when it is exhibited by introduction into the stomach. By adopting this 

 method, therefore, the existence of a lethal antagonism was subjected to a more 

 severe test than if the substances had been introduced into the stomach ; for, not 

 only are the general physiological effects produced with greater rapidity and 

 certainty, but also the lethal action of a minimum fatal dose is induced in a 

 shorter time when the substances are injected under the skin than when they 

 are introduced into the stomach. This method of administration has, besides, 

 the great recommendation of being followed by results constant as to both 

 character and time of occurrence ; for not only is the total quantity, within cer- 



