ox TIIK ANTAGONISM BETWEEN ACTIVE SUDSTANCES. 125 



111 llic latter class there are several well-autheuticated examples, among 

 which may he instanced the antagonism between the actions on the iris 

 and minute blood-vessels of opium or morphia on the one hand, and bella- 

 donna, hyoseyamus, and stramonium on the other ; between the actions ou 

 the capillary circulation of morphia and quinia ; between the actions on 

 the vagi nerves of physostigma and atropia, hydrocyanic acid and atropia, 

 and muscaria and ati'opia ; and between the actions on the iris and on visual 

 accommodation of physostigma and atropia. 



In the /o)-)He;' class the examples are likewise numerous; but a careful 

 examination of the evidence in their support cannot fail to lead to the con- 

 clusion that, with very few exceptions, it is of an unsatisfactory nature. 

 In the majority of cases where an active substance has acquired the 

 reputation of counteracting the fatal etFect of some other substance or 

 substances, this reputation has mainly been founded ou the results of 

 clinical experience. In such experience there are difhcultics in dis- 

 covering not onlj'^ what dose of poison has been introduced into the sj'stem, 

 but even when this dose has been ascertained it is generally impossible 

 to feel assured that it is a sufficient one to produce death ; and, further, 

 the effects of the substance introduced as a physiological antidote can 

 rarely be accurately observed. The exigencies of treatment demand that 

 every likely method of alleviating the symptoms should be applied ; and 

 among these it is difficult, if not impossible, to discover accurately the 

 effects of any single antidote. It is not therefore to be wondered at that 

 the accumulated clinical observations of more than two centuries should 

 have failed in itroving that opium is able to prevent the fatal effect of 

 belladonna, and that this evidence has equally failed in establishing the 

 existence of any one of the examples of lethal antagonism to which atten- 

 tion has more recently been drawn. 



A method whereby the existence of a lethal antagonism can satisfactorily 

 be tested is by experiment on the lower animals. In such experiments 

 the most important of the causes of fallacy that have been alluded to can 

 readily be avoided. It is a simple matter to determine, in any given species 

 of animal, the minimum dose of an active substance that can produce 

 death, and then to test the antidotal influence of its supposed antagonist 

 when a lethal dose of the poison has been administered. The most con- 

 vincing proof may be thus obtained of an antidotal influence ; and trusting 

 to this proof, the practitioner may with confidence employ the antidote in 

 cases of poisoning in man. It is unnecessary to show that the fallacies 

 asserted to exist in such experiments have been greatly exaggerated, or 

 that the supposed differences between the results in man and in the lower 

 animals do not possess the importance that has been claimed for them, as 

 fortunately nothing remains to be done in this direction since the con^dncing 

 arguments of Claude Bernard have been advanced and generally accepted. 



In this Iteport it is proposed to bring before the Association the results of 

 an investigation in which the influence of atropia upon the lethal action of 

 physostigma was examined, by experiments on the lower animals. The 

 nature of this influence may be shown by a brief account of two of the ex- 

 periments that were made. 



A rabbit received by subcutaneous injection a dose of extract of physo- 

 stigma considerably greater than the minimum lethal ; and one minute and a 

 half afterwards it received, also by subcutaneous injection, half a grain of 

 sulphate of atropia. In seven minutes after the injection of atropia the 

 pupils measured i-| X ^§ of an inch, the size immediately before the ex- 



