EXPERIMENTAL STUDIES ON CHEMOTHERAPEUTIC EFFECTS AND TOXICITIES OF A NEW ANTIMALARIAL DRUG 7351

7351, 2-Methoxy -7-chloro-10-(3', 5'- bis-pyrrolin-1-ylmethyl-4'-hydroxyphenyl)-amino-benzo-b-1,5-naphthyridine phosphate, a new antimalarial drug, was synthesized in 1970. This paper reports the resutls of its chemotherapeutic efficacy and toxicity.The results obtained from tests with Plasmodium berghei in mice showed that this compound, given orally or intramuscularly, possesses better schizonticidal activity than, chloroquine. No cross-resistance was observed when the compohnd was tested with chloroquine-resistant strain of P. berghei in mice. It was also shown that this compound possesses excellent schizonticidal activity against P. inui, given per os, and P. cynomolgi. and P. knowlesi by intramuscular injection or intravenous drip in monkeys.The acute toxicity of 7351 in mice, dogs and monkeys and the subacute toxicity in rats and dogs, when given by mouth, were all lower than those of chloroquine. When the compound was administrated by intramuscular injection, the acute toxicity in mice, rabbits and dogs was also found to be low.Pharmacological tests of the drug in anesthetized rabbits and dogs, given by intravenous injection revealed that the cumulative lethal dose is much higher than chloroquine.7351 was used in field trials for the treatment of malaria including patients infected with chloroquine-resistant P. falciparum and cerebral forms. The drug was administered per os or parenterally. All patients showed clinical cure. 7351 was found to be highly effective and without signifieant side-effects.