ANTIMALARIALS OTHER THAN QUININE 
265 
After 10 successive daily peroral admin¬ 
istrations of 50 mg per kg to dogs, the 
maximal concentrations were found in the 
spleen (2.75 mg per gram), the kidney 
(2.5 mg per gram) and the liver (2 mg 
per gram); the minimal in the skin (0.11 
mg per gram) the muscle (0.07 mg per 
gram) and the brain (0.035 mg per gram). 
Three weeks after a course of 5 daily 
intravenous administrations, the largest 
amounts were in the lungs (0.08 mg per 
gram), the liver (0.01 mg per kg), the 
kidney (0.004 mg per gram) and the spleen 
(0.0025 mg per gram). The organs in 
which the greatest amount is deposited 
vary with the mode of administration. 
Thus, the proportion of the atabrine con¬ 
tent in lungs, kidneys, and liver is after 
intravenous injection 3:2:1, whereas after 
peroral administration this proportion 
changes to 1:1:10. 
The pharmacological effects of thera¬ 
peutic doses of atabrine on various organs 
and organ systems are not characteristic. 
Toxic doses affect the central nervous sys¬ 
tem, causing clonic convulsions, and depress 
the respiratory and circulatory systems. 
The blood pressure is lowered (Koyu 
1937), general vasodilatation takes place 
and the electrocardiogram shows after ad¬ 
ministration of small doses slight changes 
in rhythm and a disturbance in the atrio¬ 
ventricular conductivity; large doses induce 
paroxysmal tachycardia, 2:1 heart bloc, 
ventricular flutter and fibrillation (Motta 
1937). In the isolated monkey heart 
atabrine dilates the coronary vessels, and 
causes extrasystoles and rhythmic disturb¬ 
ances (Storm 1935), which respond favor¬ 
ably to intravenous injection of adrenalin. 
Since a similar beneficial effect of adrenalin 
is observed in the heart in situ (Storm 
1935), it has been recommended that when¬ 
ever atabrine is injected intravenously, 
adrenalin should be added to the injection 
fluid in a ratio of 0.5 ce of the standard 
1:1000 solution of adrenalin to each cc 
of a 3 per cent solution of atabrine. An 
additional advantage of such a combina¬ 
tion is the vasoconstrictor effect of ad¬ 
renalin on the spleen which aids in the 
mobilization of hidden parasites. 
Atabrine exerts a moderately strong anti¬ 
pyretic effect on experimental fever pro¬ 
duced by the injection of B. coli; in the cat 
0.1 gm per kg lowers the temperature by 
0.6 to 0.9° C, the lowest point being reached 
2 hours after the peroral administration. 
Smaller doses cause occasionally transitory 
hyperthermia. 
The effect of atabrine on the uterus has 
been investigated in the isolated organ as 
well as in situ in pregnant and non-preg¬ 
nant guinea pigs, rabbits, and cats (Sapeika 
1934). In the isolated organ, concentra¬ 
tions of 1:200,000 increase the muscular 
tone and frequency of contraction, while 
1:20,000 decreases both and renders the 
uterus irresponsive to adrenalin, pilocar¬ 
pine and barium chloride. Intravenous 
injection of 1 to 4 mg per kg in a preg¬ 
nant cat is followed by a gradual increase 
of uterine contractions, which however 
return to the norm after a few minutes. 
Since these doses are proportionately many 
times larger than those administered for 
therapeutic purposes in man and since 
furthermore the latter are given by mouth 
and not injected intravenously, it is gen¬ 
erally felt that in contrast to quinine the 
use of atabrine in pregnancy is not contra¬ 
indicated. 
It would seem justified to limit a discus¬ 
sion of effective antimalarials to the 
quinine, plasmochin and atabrine group. 
Optimal therapeutic results may be ob¬ 
tained with these and the great number of 
other agents still used in the treatment of 
malaria consist either of once popular 
drugs which are prescribed through force 
of habit or of new chemicals in the state 
of clinical investigation. Although quinine 
and atabrine control effectively the schiz- 
onts of the malarial parasites and plas¬ 
mochin is equally effective as a gametocide 
in P. falciparum infection, none of them 
can be regarded as a true chemoprophylac- 
tic agent. The ideal antimalarial still has 
to be found and it is therefore obvious that 
every new chemotherapeutic agent is being 
