THEORETICAL. 
In reading the literature on the active substance of the adrenal 
gland one is impressed with the difference of the doses said to be 
lethal and of the amount of substance cited as the minimum dose 
necessar^T- to cause a rise of blood pressure. These variations; I 
believe; are to be explained in part by differences of technique but 
more especially by varjdng amounts of adrenalin in the preparations 
used by the different observers. Certainly in experiments antedat- 
ing 1900 the various workers must have been using at best only 
mixtures of adrenalin and other substances or compounds of adrena- 
lin itself. Even the epinephrin used by Amberg seems to have had 
a relatively low degree of toxicity. However; the experiments with 
epinephrin are worth repeating; perhaps there was some error in 
determining the lethal dose. If epinephrin proved to have all of the 
properties of the pure base now known as adrenalin it would be pos- 
sible to adopt this name for the active substance of the adrenal gland; 
which from many standpoints is to be preferred above all others. As 
stated earlier in this paper; Battelli Avorked with an unusually pure 
product; and while it is not altogether safe to compare results 
obtained with animals so widel}^ different as mice and rabbits still 
it is interesting that the lethal doses given in this paper and those 
cited by Battelli are Amry nearly alike; Viz., 8 to 10 milligrams per 
kilogram for subcutaneous injections. 
It is also interesting that the relathm pharmacological activity of 
the four compounds; as determined by any given method — say blood 
pressure; toxicit}^; or pupil experiments — should bear to each other 
a rather definite ratio. And Avhen the difference in relative degree 
of toxicity or of A^aso-constrictor activity seems to be closely asso- 
ciated Avith certain groups in the molecule or to contain arrangements 
of these groups in space it becomes very suggestiAm from a theoretical 
standpoint. 
As already pointed out the natural 1-adrenalin has a A^aso-constric- 
tor action one and a half times as poAverful as synthetic dl-adrenaliii; 
and nearly the same action as ortho-dioxy-phenyl-ethanol-amin 
(arterenol); but eighty times as poAA^erful as ortho-ethyl-amino- 
dioxy-aceto-phenon (homorenon); thus making the relative activity 
of these substances to each other as the inverse ratio of 1:15:1: 80. 
If; on the other hand; the relative toxicity of the substances just 
named be compared it will be found that they are to each other as 
the inverse ratio of 1 : (1.5-2) : 5: (71-80). In comparing these ratios 
it Avill be seen that they are nearl}^ alike; the diA^ergence being in 
that part of the toxicity ratio pertaining to arterenol. This product; 
though causing nearH the same rises of blood pressure as the natural 
( 68 ) 
