70 
we have a good illustration of the effects of changing the composi- 
tion of the side chains. In (1) the composition is the same as (2), 
with the exception that one hydrogen is chsplaced by the methyl group 
wliile in (3) one hydrogen of the amino group is displaced by an ethyl 
group and the side chain joined to the catechol nucleus through a car- 
boxyl group instead of a secondary alcohol group. Evidently, it is the 
nature of this side chain that determines the degree of activity as 
well as its relation. I agree with Dakm in liis contention that the 
hydrogen atoms of the hydroxyl groups must be unsubstituted, that 
alkyl groups of low molecular weight tend to increase the activity 
much more efficiently than when larger molecules are introduced mto 
the side chain. Indeed, several factors seem to be of prime importance 
in determining the activity of catechol compoimds. (1) TYIiether 
the substance partakes of the nature of a ketone or of a secondary 
alcohol, the latter being the more active: (2) the nature of the 
groups chsplacing the H of the amino groups, as well as the number 
of displacements; and (3) the arrangement of the asymmetric carbon 
atom in space, the l^vo arrangement usually being an index of the 
greater activity. At least this is borne out by my own results and 
by the results of Cuslmy and others. 
With the theory that these are the determining factors in modifying 
the vaso-constrictor action of such compounds it is hoped that as a 
working basis it ^vill aid in a more extended study of other com- 
pounds possessing physiological activity. 
coxcnrsioxs. 
1. The blood-pressure method with dogs under morpliine-ether 
ansesthesia, the vagi cut, and very small doses of curare, is the most 
accurate pharmacological assay for catechol derivatives. 
2. The pupil method as modified by the author is a rehable assay 
for adrenahn but less dehcate and more tedious than the blood- 
pressure method. 
3. Synthetic dl-adrenalin is less active as a vaso-constrictor and as 
a mydriatic than natural 1-adrenalin, the ratio being 2:3. 
4. The relative vaso-constrictor activity of the catechol derivatives 
in the order named, 1- and dl-, ortho-dioxyphenylethanolmethylamin, 
ortho-dioxyphenylethanolamin and ortho-ethvlaminodioxyacetophe- 
non are to each other as the inverse ratio of 1:1.5:1:80. 
5. The toxicity of the substances in the order named in (4) are to 
each other as the inverse ratio of 1: (1.5 to 2):5:(71 to 80). 
6. The relative physiological acthnty of these catechol derivatives 
seems to depend upon the substance partaking of the properties of a 
secondary alcohol or of a ketone, upon the nature and number of 
groups displacing the hydrogen of the amino group, and upon the 
arrangement of the asymmetric carbon in space. 
