256 
MALARIA 
occurs when the unsaturated vinyl group¬ 
ing .is replaced by the saturated chain 
- CH 2 • CH 3 . Alkyl substitution for the R 
of dihydrocupreine gives rise to a series of 
substances much studied for their chemo¬ 
therapeutic action (optochin, eukupin, 
vuzin) but of no present interest because 
of their lack of any important degree of 
action against the malarial plasmodium. 
These chemical relationships are shown in 
Table I. 
to alkaloids of the opposite sign (Dawson 
et al. 1933). 
The historical aspects of the use of cin¬ 
chona have recently been reviewed by 
others (Dawson 1930, Fischl and Schloss- 
berger 1932) and will not be discussed here. 
Up until the introduction of plasmochin 
(1926) and atabrine (1933) preparations of 
cinchona or its alkaloids were the only 
established substances for the specific treat¬ 
ment of malaria. Although these newer 
TABLE I 
The Principal Cinchona Alkaloids 
(Fisehl and Schlossberger 1932, p. 153) 
Formula 
Sign of rotation 
Substitutions 
Laevo 
Dextro 
E 
E' 
CjoH^ONa 
Cinchonidine 
Cinchonine 
H 
CH = CH a 
C^H^OaNa 
Cupreine 
Cupreidine 
OH 
CH = CH 2 
CaoH^OaNa 
Quinine 
Quinidine 
och 3 
CH = CH 2 
C 19 Ha,ON 2 
Hydrocinchonidine 
Hydrocinchonine 
H 
ch 2 ch 3 
C 1( ,H m 0 2 N 2 
Hydro cupreine 
Hydrocupreidine 
OH 
ch 2 ch 3 
C'2)ttM0 2 N 2 
Hydroquinine 
Hydroquinidine 
och 3 
ch 2 ch 3 
CaaKsAN., 
Optochin 
och 2 ch 3 
ch 2 ch 3 
There are four asymmetric carbons in 
the formula given in Fig. 1. This of course 
gives rise to the possibility of isomerism 
among the members of the group. Thus, 
quinine and quinidine form a pair, differ¬ 
ing only by the sign of rotation of polarized 
light. Similarly, cinchonidine and cin¬ 
chonine form a pair. However, it has not 
been possible to relate therapeutic effective¬ 
ness of the alkaloids against the malarial 
organisms to the sign of rotation. Often 
it is the case that the laevo-rotatory member 
of a pair of isomers has the greater bio¬ 
logical activity. This certainly does not 
hold for the quinine-quinidine pair. Such 
information as is available indicates that 
in the treatment of malaria they are essen¬ 
tially equivalent (vide infra), while in 
toxicity and depressing effect on the vari¬ 
ous parts of the circulatory mechanisms the 
dextro-isomer quinidine is clearly the 
stronger member of the pair (Nelson 1927a). 
The chief significance of the isomerism lies 
in the fact that idiosyncrasy to alkaloids 
of one sign does not necessarily carry over 
substances are apparently coming to be of 
greater and greater importance, quinine 
still holds a major place. A recent report 
of the Malaria Commission of the Health 
Organization of the League of Nations 
(1937) carries the following statement in 
its conclusion: “Among those drugs [ i.e 
those used for curative or prophylactic mass 
treatment] quinine still ranks first in cur¬ 
rent practice by reason of its clinical effec¬ 
tiveness and almost complete absence of 
toxicity, coupled with widespread knowl¬ 
edge of its use and dosage” (page 1015). 
While historically the use of bark or of 
galenicals made from it in the treatment 
of malaria is of considerable interest, such 
preparations do not play any important 
role in the treatment of malaria by organ¬ 
ized medical and public health agencies in 
this country. In other parts of the world 
the necessity for supplying drugs for mass 
treatment at the lowest possible cost has 
led to the introduction of the use of extracts 
of bark without complete separation and 
isolation of the alkaloids. The Malaria 
