Primaquine is the only currently available
drug effective against persistent tissue stages of relapsing
malaria in humans. Causal prophylactic and radical curative properties of
WR182393 (a guanylhydrazone) were investigated as part of an effort to evaluate alternatives to
primaquine in the rhesus monkey (Macaca mulatta)/Plasmodium cynomolgi test model. The
drug was suspended in
dimethylsulfoxide for intramuscular (im) injection. A pilot study indicated causal prophylactic activity in a regimen of 40 mg base/kg/day im for three days beginning the day before intravenous challenge with 1 x 10(6) P. cynomolgi sporozoites. Regimens of 31, 10, 3.1, and 0 mg base/kg/day im for three days were then tested in groups of two monkeys given a similar challenge. The two animals given 31 mg base/kg/day remained parasite-free. Average time to
parasitemia for the lower dosage groups was 38, 18, and 8 days respectively. Groups of two monkeys with sporozoite-induced P. cynomolgi
infections were also treated for seven days with 31, 10, 3.1, and 0 mg base/kg/day im in combination with 10 mg base/kg/day of
chloroquine orally. Both monkeys given 31 mg base/kg/day did not relapse. The average time to relapse following treatment was 48, 29, and 8 days, respectively, for the lower dosage groups. Compound
WR182393 is the first non-8-aminoquinoline class of
drug to exhibit both causal prophylactic and radical curative properties against a relapsing primate, vivax-like
malaria.