PRERTDKNTIAL APPRRRR. 473 



fart that while it is possesserl by the tetramethyl ammnninm salts, the tetra- 

 ethyl-<aninioiiiuin hnmologiies aie ♦entirely devoid of it. 



Another close relationship is shown by the reaction of the glncosides of the 

 digitalis series on the heart and vessels. These all act on the mnscle of the 

 heart, and in higher concentration on that of the vessel-walls. There must 

 thei'efore be a common base in. these which is affected by the drugs. And the 

 existence of this is perfectly intelligible in view of the fact that the heart is 

 developed from the vessels. A more obscure relationship is shown by the 

 reaction of this group to the inhibitory cardiac centre in the medulla, which is 

 thrown into abnormal activity by their presence in the blood, as has been shown 

 alike by clinical and experimental observations. A similar relation is shown 

 by the common reaction of the heart-muscle and the vagus centre to aconitine 

 and some other related alkaloids. On the other hand, the saponin series, which 

 shows a closer relationship to the digitalis bodies in the heart-muscle, is devoid 

 of its characteristic action on the medulla. The reacting substance in the heart 

 is tRus capable of responding to digitalis, saponin and aconitine, while that 

 in the vagus centre can associate only the first and last and is not affected by the 

 saponins; the connnon reactions indicate that the two are related, while the 

 distinctive effect of .saponin shows that they are not identical. A similar 

 relationship may be drawn from the action of morphine and the other opium 

 alkaloids on pain sensation, on respiration, and on the movements of the 

 alimentary tract. Exact determinations of the relative power of these alkaloids 

 in these regions are not at our disposal as yet, but sufficient is known to suggest 

 that while morphine affects a common substance in the medullary centre and 

 the liitestinal wall, the other members of the series act more strongly in one or 

 other position. 



It was long ago pointed out that caffeine affects both kidney and muscle- 

 cell, and Schmiedeberg has attempted to correlate the intensity of action of the 

 purine bodies at these points and to measure the probable diuretic action by the 

 actually observed effect on the contraction of muscle. Other reactions of the 

 kidney suggest a relationship to the wall of the bowel. For example, many of 

 the Tieavy metals and some other irritant bodies act strongly on the kidney and 

 bowel, and asain, according to one view of renal function, many of the simple 

 salts of the alkalies affect the kidney in exactly the same way as the bowel- wall. 

 This last may, however, be due to the physical properties of the salts, and the 

 likeness in reaction to those of kidney and bowel, which is striking enough, 

 may arise rather from a likeness in function of the epithelium rather than from 

 any specific relationship to the salts which is not common to other forms of 

 living matter. 



IMany other examples might be cited in which organs which are apparently 

 not related, either morphologically or in function, react to poisons in quantities 

 which are indifferent to the tissues in general. And this reaction in common 

 can only be interpreted to mean that there is some substance or group of related 

 substances common to these organs. The reaction may differ in character ; thus 

 a drug which excites one organ to greater activity may depress another, but 

 the fact that it has any effect whatever on these organs in preference to the 

 tissues in general indicates some special bond between them, some quality which 

 is not shared by the unaffected parts of the body. I have, therefore, not 

 differentiated between excitation and depression in discussing this relation. 

 One is tempted to utilise the nomenclature introduced by Ehrlich here, and to 

 state that the common reaction is due to the presence of haptophore groups 

 while the nature of the reaction (excitation or depression) depends on the 

 character of the toxophore groups. But while these terms may be convenient 

 when applied to poisons whose chemical composition is altogether unknown, they 

 merely lead to confusion when the question concerns substances of ascertained 

 structure. Thus, as Dale has pointed out. it is impossible to suppose that such 

 substances as tetramethyl-ammonium and tetraethyl-ammonium owe the difference 

 in reactions to specific haptophore groups in the one which are absent in the other. 

 Tt seems more probable that in this instance and in others the difference in 

 the effect of these bodies in the tissues arises from differences in the behaviour 

 of the molecule as a whole than in differences in the affinities of its special 

 parts: that is, that the action of these poisons is due to their physical properties 

 rather than to their chemical structure, although this, of course, is the final 

 determining cause. 



