192 DRS CRUM BROWN AND FRASER ON THE CONNECTION BETWEEN 



Some experiments were made to determine, for our satisfaction, the physio- 

 logical effects of iodide of methyl. The only bearing of these on the present 

 investigation is, that no evidence was obtained in support of the extremely impro- 

 bable hypothesis, that some of the changes produced in the action of the sub- 

 stances we have described might have been due to addition of the physiological 

 action of the methyl compounds. 



We have thus shown that chemical addition produces some important modi- 

 fications in the action of those poisons which have been treated of in this com- 

 munication. The action of strychnia, brucia, thebaia, codeia, morphia, and 

 nicotia is evidently greatly diminished in degree, and, at the same time, strikingly 

 changed in character. 



The former effect is shown with all these alkaloids, especially when their 

 action is compared with that of the iodides of their methyl derivatives. As all 

 these iodides are much less soluble than the salts of the alkaloids themselves, 

 it might be supposed that the diminution in activity could be explained by 

 this difference in solubility. Some support is given to this supposition, by 

 examining the relations between various of the substances included in this 

 investigation. Thus, it has been demonstrated, on the one hand, that, for rabbits, 

 the fatal dose of iodide of methyl-strychnium administered subcutaneously, is 

 about twenty grains, and that of iodide of methyl-thebaium is about ten grains ; 

 while the former is soluble in 133 parts of distilled water, at a temperature of 

 37° C, and the latter in 1G5 parts at the same temperature. On the other 

 hand, the fatal dose for rabbits, of sulphate of methyl-strychnium, is about 

 four-fifths of a grain, and that of sulphate of methyl-thebaium is about five 

 grains ; while both substances are freely soluble, and with nearly equal readi- 

 ness, in cold water. In these examples, the greater activity of strychnia over 

 thebaia is manifested when a soluble salt of the methyl derivative of strychnia 

 is employed ; but when an extremely insoluble salt — the iodide — is employed, 

 its activity is nearly the same as that of a corresponding preparation of 

 thebaia; although the latter alkaloid is itself considerably less energetic than 

 strychnia. It is, therefore, apparent that poisonous activity may be modified by 

 the degree of solubility,— a well-recognised principle in toxicological physiology. 

 But while the diminished activity of the iodides of many of these methyl deriva- 

 tives may be greatly due to the difficulty of dissolving them, this explanation is 

 inapplicable to iodide of methyl-nicotium, — an extremely soluble substance, — and 

 it is insufficient to account for the differences of activity between the majority of 

 the sulphates of the methyl derivatives and the salts of the alkaloids themselves. 

 Our investigation has not furnished us with any explanation of the change in 

 these sulphates. There are several possible explanations, but we shall not 

 specially allude to them, as their discussion can only be properly undertaken 

 after experimental examination of a laborious and difficult nature, and but indi- 



