82 A. P. MATHEWS 



plasm, although they do not dissociate electrolytically into ions in the 

 ordinary sense of the term. To explain the action of such compounds 

 as ether and organic drugs, either one must fall back upon the assump- 

 tion of the action of undissociated molecules, or the idea of dissociation 

 must be extended to cover dissociation which is not accompanied by 

 electrical conductivity. Kahlenberg and True, and indeed nearly all 

 observers, have adopted the theory that some action must be ascribed 

 to undissociated molecules; but it appears to me, in view of the fact 

 that such another kind of dissociation is well known to occur as, for 

 example, the dissociation of NH 4 OH into NH 3 and H 2 O and also 

 that this dissociation has been shown by Nef * to determine the chemi- 

 cal reactions of such compounds, that the alternative of the action of 

 dissociated particles is the more probable. At any rate, it would be 

 premature to ascribe pharmacological action to undissociated mole- 

 cules until the possibilities that that action is due to the dissociated 

 particles shall have been proved to be insufficient. In the present 

 paper I shall deal with pharmacological action due to particles dis- 

 sociated as ions, and in a subsequent paper to action due to non-ionic 

 dissociation. The general principles which I have worked out apply 

 primarily to ionic particles, but I think it altogether probable that 

 they will be found to apply equally well to non-ionic dissociation, 

 since there is in all likelihood no essential difference in kind between 

 such dissociation as that of NH 4 OH into NH 3 and H 2 O and ionic 

 dissociation. The two probably differ only in that in the one case 

 the two electrical charges are on the same particle, whereas in ionic 

 dissociation they are on separate atoms. 2 



While, then, it cannot be denied that some action may be referable 

 to undissociated molecules, the clear parallelism between dissociation 

 and pharmacological action in the case of salts, and the equally clear 

 parallelism between non-ionic dissociation and pharmacological action 

 in organic compounds, indicates to my mind that it is to these disso- 

 ciated particles as the possible cause of pharmacodynamic action that 

 attention should first be directed. 



Assuming, therefore, that the action of salts is due in chief meas- 

 ure to the ions of the solution, the first question to be answered is: 



1 NEF, Liebig's Annalen, 1904, 335, p. 192. 



MATHEWS, Biological Bulletin, 1905, 8, p. 342. See also NERNST, Theorctische Chemie, 4th ed., 

 1903. P- 378. 



