262 
MALARIA 
parasites, which are necessary for the 
propagation of the disease in the carrier mos¬ 
quito. However, the fact that the adminis¬ 
tration of plasmochin is safe only under 
constant medical supervision presents a 
serious obstacle to this form of malarial con¬ 
trol. Unlike as in quinine prophylaxis, it 
seems generally agreed that the administra¬ 
tion of plasmochin must be restricted to 
patients who can be seen regularly by a 
physician. 
Toxicity. The toxicity of plasmochin 
has been investigated in most laboratory 
animals (LeHeux and van Wijndgaarden 
1929; Tskimanauri 1931). It varies con¬ 
siderably with the species, not only quan¬ 
titatively but also qualitatively. Two forms 
of symptoms are generally observed, one 
with an acute onset of the toxic signs shortly 
after administration of the drug and a pre¬ 
ponderance of nervous, circulatory and 
respiratory disturbances; the other, a more 
delayed type, with cyanosis, methemoglo¬ 
binemia and eventual respiratory failure. 
The acute type prevails in rabbits and 
canaries, while in mice, cats and dogs more 
often the delayed type is found; animals, 
which have recovered from the shock im¬ 
mediately following administration of a 
lethal dose of plasmochin may still succumb 
several hours or even days later from 
methemoglobinemia. This is particularly 
the case after peroral administration of 
the drug. 
The difference between the peroral, sub¬ 
cutaneous and intravenous toxicity of 
plasmochin is not very great except in the 
rabbit, for which the peroral toxic dose is 
60 to 70 times, the subcutaneous 5 to 6 times, 
larger than the intravenous. Prolonged 
intravenous or subcutaneous administration 
of plasmochin in therapeutic doses causes 
no pronounced toxic effects (Tskimanauri 
1931). After the first few doses, the ani¬ 
mals show a temporary loss of weight which, 
however, later becomes stabilized. Com¬ 
bination of plasmochin with quinine 
(known as Quinoplasmin or plasmochinum 
compositum) which has often been advo¬ 
cated in order to improve the therapeutic 
effectiveness, does not change the toxicity 
of plasmochin (Le Heux and de Lind van 
Wijndgaarden 1928). 
The pathological findings in animals dy¬ 
ing from excessive doses of plasmochin are 
unspecific and due mainly to the methemo¬ 
globinemia. They consist of a brownish 
discoloration of the lungs, muscle, omentum, 
and mucous membranes. In dogs, cats and 
canaries the intestines are hyperemic and 
the blood vessels of the adbominal region 
are markedly dilated. 
The formation of methemoglobin is one 
of the most pronounced toxic effects of 
plasmochin. It occurs in man after daily 
administration of 0.08-0.1 mg (Fischer 
and Rheindorf 1928) and is readily ob¬ 
served in most animal species (horses, cows, 
sheep, pigs, cats, dogs), with the exception 
of rabbits and mice, in which it occurs only 
after the blood has been hemolyzed (Le 
Heux and de Lind van Wijndgaarden 1928). 
The minimal blood concentration of plas¬ 
mochin causing methemoglobin formation 
is 1:12,500 in cats and dogs, 1:1500 in rab¬ 
bits. In the latter, peroral doses of 6 mg 
per kg convert up to 7 per cent; 22 mg 
per kg up to 40 per cent of the total hemo¬ 
globin into methemoglobin (Messini 1928). 
However, the methemoglobin formation is 
reversible in vivo as well as in vitro (Le 
Heux and de Lind van Wijndgaarden 1928) ; 
all signs disappear after discontinuation of 
the drug (Messini 1928) and the process is 
not associated with an increased destruc¬ 
tion of erythrocytes or damage of the liver, 
as evidenced by negative bilirubin and 
urobilinogen tests even at the height of the 
methemoglobinemia. Plasmochin in con¬ 
centrations greater than 1:5000 causes 
hemolysis in vitro (Le Heux and de Lind 
van Wijndgaarden 1928). 
The effect of plasmochin on the blood 
pigments is not its only toxic property. 
Far more serious is its adverse effect upon 
the circulatory system, which is found in all 
species, including man, and which may be 
observed in the isolated organs as well as 
in situ. In the isolated frog and rab¬ 
bit’s heart concentrations of 1:250,000 up 
to 1:1 million induce irregular beat; 
1:100,000 caused an irreversible diastolic 
