§ 30.] TOXIC ACTION AND CHEMICAL COMPOSITION. 41 
this substance contains the skeleton of adrenaline, differing from 
it in lacking the two hydroxyls of the benzene nucleus, the hydroxyl 
of the /2-carbon atom, and the methyl group attached to the nitrogen 
atom. The effect of an hydroxyl attached to the /2-carbon atom, 
of attaching a methyl group, and lastly of a /3-hydroxyl to the 
methylated molecule caused neither increase nor decrease in activity. 
It remained, therefore, to study the influence of hydroxyl groups in the 
phenol nucleus. They found ^-hydroxy-/3-phenylethylamine as well as 
the rneta compound three to five times as active as /3-phenylethylamine, 
but the ortho-substituted compound showed no increase. 
The net result of the investigation led to the following conclusions :— 
“ The optimum carbon skeleton for sympathomimetic activity consists of 
a benzene ring with a side chain of two carbon atoms, the terminal one 
bearing the amino group. Another optimum condition is the presence 
of two phenolic hydroxyls in the 3-4 position relative to the side chain ; 
when these are present an alcoholic hydroxyl still further intensifies 
the activity. A phenolic hydroxyl in the ortho position does not 
increase the activity.” 
That among the amines the optimum side chain has two carbon 
atoms between the cyclic system and the amino group is well illustrated 
by the intense activity as a stimulant of pale muscle of 4-/2-amino-ethyl 
glyoxaline (see Ergot) (C 3 H 3 N 2 .CH 2 .CH 2 .NH 2 ). 4-/3-amino-methyl 
glyoxaline (C 3 H 3 N 2 .CH 2 .NH 2 ) has only one separating carbon group, and 
4-y-amino-butyl glyoxaline has three separating carbon groups. Both 
of these substances show a great diminution of activity. 
§ 30. Proto-zoacidal Drugs. —These are substances which have 
a toxic action on certain lower forms of parasitic life within the 
bodies of mammals, and the ideal of perfection is that the drug will 
have the maximum amount of lethality for the parasite without causing 
any inconvenience to the host—an ideal partly attained by certain 
organic compounds of arsenic in the treatment of syphilis, by the cin¬ 
chona alkaloids on the plasmodia in the blood of malarious persons, 
and by emetine on the Entamoeba histolytica in amoebic dysentery. 
With regard to malaria, clinical observation has shown that the following 
is the order of activity of six quinine alkaloids :— 
Most active. 1. Hydroquinone hydrochloride MeO.C 17 H 18 ON 2 .CH 2 CH 3 . 
Nearly equal \ 1 Cinchonine (sulphate) H.C 17 H 18 ON 2 .CH : CH 2 . 
activity, but l 2. j Quinine (sulphate) MeO.C 17 H 18 ON 2 .CH : CH 2 . 
less than No. 1. J ( Quinidine (sulphate) MeO.C 17 H 18 ON 2 CH : CH 2 . 
3. Ethyl-hydrocupreine (hydrochloride) EtO.C 17 H 18 ON 2 . 
ch. 2 ch 3 . 
4. Cinchonidine (sulphate) H.C 17 H 18 ON 2 .CH : CH 2 . 
No. 3 is more toxic to protozoa in vitro than any other of the six, but 
nevertheless clinical research has shown its inferiority to Nos. 1 and 2. 1 
1 A. C. Mac Gilchrist, Ind. J. Med, Res., xix. 4, 1915, 
