126 REPORT — 1872. 



periment having been -^-q- X ify- of an inch ; the rate of the heart's contractions 

 ■was considerably accelerated ; fibrillary twitches were occurring, and a little 

 restlessness was present. Soon afterwards the pupils became still further 

 dilated, and the animal had some difficulty in moving about. In fifty-two 

 minutes the pupils measured -g-^- X ^^^ of an inch, and the difficulty in moving 

 about had become greater. In one hour and ten minutes, however, evidences 

 of recovery wej'e manifested; the animal went about with but little difficulty, 

 and frequently a perfectly normal sitting posture was assumed. Indeed the 

 only symptom of an abnormal character that was now apparent consisted 

 of frequently occurring and well-marked fibrillary twitches. From this 

 time the condition of the animal steadily improved, until perfect recovery 

 occurred. As the minimum lethal dose of this preparation of physostigma, 

 for any given weight of rabbit, had been determined by a preliminary series 

 of experiments, it was known that the dose given in this experiment was 

 rather more than twice as large as the minimum lethal. Yet the fatal eff'ect 

 of this large dose was prevented in a remarkable manner by the dose of 

 atropia given in conjunction with it. To add to the proof that was thereby 

 obtained, of an antagonism between these two substances, there was ad- 

 ministered to this rabbit, nine days afterwards, a dose of extract of physo- 

 stigma, only half as large as that from which it had thus recovered. Symptoms 

 of poisoning very quickly appeared, and death occurred in about fourteen 

 minutes. 



In the second experiment, a dog, Aveighing ten pounds and three ounces, re- 

 ceived by subcutaneous injection three fifths of a grain of sulphate of ph3'-so- 

 stigmia, dissolved in a few drops of distilled water. Before the injection the rate 

 per ten se onds of the cardiac impulses was 32, and that of the respirations 4, 

 and the size of the pupils was 4-2_ ^ ^a of an inch. In four minutes after the 

 administration of physostigma slight tremors occui'red, and fibrillary twitches 

 were present. In five minutes a solution containing three tenths of a grain 

 of sulphate of atropia was injected under the skin. In two minutes there- 

 after the tremors had become more prominent and strong, the hmbs were un- 

 able properly to support the body, saliva escaped from the mouth, and the eye- 

 balls were unnaturally moist. In five minutes the pupils were greatly 

 dilated ; but now the secretions of the salivary and lachrymal glands were 

 diminished. In seven minutes the dog lay quietly on the abdomen and chest, 

 but in thirteen minutes it fell over on the side. This general condition re- 

 mained until forty-eight minutes, when the symptoms improved ; and after 

 some efforts the dog rose, and then lay down in a normal crouching posture. 

 Soon afterwards it again got up and walked about the room with only a Httle 

 unsteadiness. In one hour and fifty-five minutes the animal seemed to be 

 perfectly well. 



Nineteen days after the performance of this experiment, the same dog 

 received by subcutaneous injection a dose of suljihate of physostigmia only 

 one half as large as that from which it had recovered when atropia was 

 also given, and the result was that death was produced in twcntj'-two minutes. 



-It; is manifest that in these two experiments atropia acted as a physio- 

 logical counteragent to the toxic action of physostigma. In other 195 ex- 

 periments the fatal cifect of undoubtedly lethal doses of physostigma was 

 likewise -prevented by atropia.- This investigation has therefore proved that 

 atropiar is a eounterageut to the lethal action of physostigma. 



As both of these substances possess a number of separate actions, it was not 

 unreasonable to anticipate that several of them are not mutually antagonistic, 

 and therefore that combinations of certain doses of the tM'o substances mav 



