12 
times used. Five-tenths gram of the fresh gland in the form of a glyc- 
erine extract injected into the dorsal lymph sack of the frog caused im- 
mediate paralysis, from which the animal soon recovered, doses up to 
3 gm. not proving fatal. With toads much larger doses were required 
to produce corresponding symptoms. Doses equivalent to 1.5 and 
3 gm. of fresh gland caused in rats the usual cardiac, respiratory, 
and nervous symptoms, some of the animals recovering, others 
d}dng from failure of respiration. Guinea pigs of average weight 
were injected with an equivalent of 6 gm. of fresh gland, the symp- 
toms being practically the same as for cats and mice, except that 
the urine of the former was more blood colored (with or without corpus- 
cles) . The fatal dose for rabbits can not be stated, since they vary so 
much in reaction. Unlike the guinea pig, which becomes very restless, 
the rabbit grows drows}” and listless. Small initial doses followed 
by one that was usually fatal for fresh rabbits no longer proved to 
be so. Vincent thinks that a partial immunity (tolerance) is estab- 
lished toward the toxic action of the extract, which passes off after 
a few weeks. 
In the meanwhile Abel (1899), Von Furth, and others had been 
working upon the chemistry of the active principle. The former 
isolated a substance which he called ^ ^ epinephrin ; ” the latter a 
substance which he called ^^suprarenin.*’ A controversy arose as to 
which was the active principle. As a matter of fact, neither chemist 
seemed to be working with the pure substance. They did, however, 
throw much light upon the chemistry of the compound, and prepared 
the way for its separation by Takamine (72) (1901) and by Aldrich (4) . 
Moore and Purinton (60) (1899) criticized the idea of epinephrin 
(Abel), suprarenin (Von Furth), and the other so-called pure products 
being the active principle. They record a rise of blood pressure after 
intravenous injections of the crude medullary extract in doses 
ranging from 0.245 to 24 millionths of a gram per kilo. This, they 
maintain, represents a physiological activity far in excess of any of 
the so-called active principles. 
In reply to Moore and Purinton’s criticism. Hunt (41) determined 
the minimal amounts of Abel’s epinephrin sulphate necessary to 
cause a rise of blood pressure, finding that even'so small an amount 
as 0.083 millionths of a gram per kilo body weight caused a rise of 
5 mm. of mercury, and 0.23 millionths of a gram per kilo, a rise of 
7 mm. The duration of the injection period (in this case two to 
five seconds) was found a very important factor in determining the 
degree of vaso-constriction resulting from a given dose of adrenalin. 
One and one-tenth millionths of a gram per kilo injected rapidly 
might cause a rise of blood pressure equal to 14 mm. of Hg., whereas 
double this dose injected slowly caused a rise equivalent to but 8 mm. 
