ANTIMALARIALS OTHER THAN QUININE 
By HANS MOLITOR 
MERCK INSTITUTE FOR THERAPEUTIC RESEARCH, RAHWAY, NEW JERSEY 
Medicinal agents other than quinine 
used in the treatment of malaria may be 
divided in three groups: (a) synthetic com¬ 
pounds with a specific chemotherapeutic, 
action against the malaria parasites and 
structurally related to quinine; (b) syn¬ 
thetic compounds with a specific chemo¬ 
therapeutic effect against malaria parasites, 
but structurally not related to quinine; (c) 
drugs of synthetic or natural origin with 
general chemotherapeutic activity, but not 
specifically directed against the malarial 
parasites. 
The introduction of synthetic compounds 
with antimalarial properties, equal or 
superior to those of quinine, is one of the 
greatest triumphs of systematic chemothera¬ 
peutic research and the first real advance¬ 
ment in the field of antimalarial therapy 
since the introduction of quinine. The 
credit for this achievement belongs to a 
group of workers at the Research Labora¬ 
tory of the I.G., the great German chemical 
trust. The work of these men, among whom 
Horlein, Eikuth, Mietzch, Roehl, Schoen- 
hofer, Schulemann and Wingler are prom¬ 
inent, opened new approaches to malarial 
therapy and led to the synthesis of thou¬ 
sands of compounds by chemists in all parts 
of the world. However, none of the com¬ 
pounds made since the introduction of 
Plasmochin in 1928 and Atabrine in 1933, 
has proved superior to these two agents; 
and for brevity’s sake we may therefore 
confine our discussion to them. 
Plasmochin 
The structure of plasmochin is chemi¬ 
cally somewhat related to that of quinine, 
being an amino quinoline derivative (N-di- 
ethylaminoisopentyl-8 - amino - 6 - methoxy- 
quinoline (C 2 H 5 ) 2 N (CH 2 ) 3 CH (CH 3 ) NH 
CH 3 0 C9H5N) . However, Schulemann and 
his co-workers (1927) who synthesized the 
compound, arrived at it not through an 
attempted modification of the original 
quinine molecule, but rather through an 
alteration of the structure of methylene 
blue, the antimalarial properties of which 
had already been recognized by Ehrlich in 
1891. 
Plasmochin is one of the most specific 
and potent antimalarials. Its effective dose 
in Proteosoma praecox infected canaries, 
when administered daily by mouth for 6 
days, is 0.02 mg, and its lethol dose is 
0.6 mg per bird (Roehl 1926). The cor¬ 
responding figures for quinine hydro¬ 
chloride are 1.25 mg and 5.0 mg, respec¬ 
tively. Thus, its chemotherapeutic in¬ 
dex is 1: 30, as compared to that of quinine 
1:4. In experiments in vitro, a concentra¬ 
tion of plasmochin of 0.2 mg per cc will 
kill P. praecox after incubation for 1 hour, 
as compared to 0.5 mg per cc of quinine 
(Borchardt 1930). In a comparison of the 
effect of quinine and plasmochin on pro¬ 
teosoma infected canaries, a peroral dose of 
0.01-0.1 gm of plasmochin greatly reduced 
the number of merozoites as well as their 
rate of formation, while a peroral does of 
0.25 to 0.5 gm of quinine only reduced their 
number, but did not materially alter their 
rate of formation (Boyd and Dunn 1939). 
Although exerting but slight effect on 
schizonts of the parasites of tertian and 
quartan, it possesses a powerful action 
against the gametocytes of P. falciparum 
(Roehl 1926; Kikuth 1932) and even in 
minimal doses renders them non-infectious 
for mosquitoes. (Barber, Komp and New¬ 
man 1929b). This gametocidal effect is not 
manifested by quinine, which possesses only 
antischizontic properties. The systematic 
administration of plasmochin to carriers of 
tropical malaria should greatly aid in the 
eradication of this disease through the 
destruction of the sexual forms of the 
