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(an 8-aminoquinoline), atabrine (a 9-aminoacridine structurally similar to
chloroquine) and sontochin (methylated chloroquine, sold today as Niva-
quine). These drugs became the templates for modern antimalarial therapies
used for most of the second half of the twentieth century. During this criti-
cal period of discovery (1920-1940), neither American nor British science
brought any important technical advances or drugs to bear on the malaria
problem ( Greenwood, 1995 ). These governments showed little interest in
improving upon quinine therapy, a view that would radically change with
their loss of access to Java and its cinchona plantations.
Pamaquine was licensed and commercially distributed during the 1920s
(as plasmochin or plasmoquine) for treatment of acute malaria. It became
known as relatively toxic and never threatened quinine's commercial primacy.
Later practitioners realized they could give lower doses of pamaquine with
quinine co-therapy and achieve superior results more safely - unwittingly
inventing radical cure with blood schizontocide and hypnozoitocide before
the existence of that liver stage was known. Pamaquine tablets contained
20 mg base drug, and treatment of acute malaria with this drug alone typi-
cally consisted of three tablets daily for 5-10 days. The therapy was later for-
mulated in tablets containing 10 mg pamaquine and 125 mg quinine sulfate,
again three daily doses for as many days (5-10) ( Brosius, 1927 ). Practitioners
noted, even at the lower dose of pamaquine, gastric upset, cyanosis, and, in
a minority of patients who tended to be African in origin, black urine as
the principal toxic effects. In 1937, the Malaria Commission of the League
of Nations recommended against using pamaquine (despite a 1933 position
endorsing its wide use) in writing, '… no chemotherapeutic remedy should be used
for general purposes unless it will comply with the requirement that the dose which
kills the parasite is very much smaller than the dose which the human host will tolerate
without injury, and unfortunately, plasmoquine cannot yet be classified as a drug which
fulfills this requirement' . (quoted in ( Field, 1938 )). Pamaquine was effectively
abandoned as a viable therapy.
Field (1938) describes efforts by French and Russian scientists to miti-
gate pamaquine toxicity by modifying the length of the alkyl chain - safer
compounds, such as Russian plasmocide, seemed less effective, however. A
French version of pamaquine (having one fewer carbon in its alkyl chain),
rhodaquine, was apparently widely used in French colonies ( Field, 1938 ).
Atabrine (also called atebrin or mepacrine) was synthesized in 1931 at
Elberfeld. The French and Russians produced replicas dubbed quinacrine
(exact) and acriquine-8 (lacking a methyl group in the alkyl side chain),
respectively. The French authorities forbid the purchase of atabrine in lieu
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