Tissue schizontocidal action and acute toxicity of trifluoroacetyl primaquine

Trifluoroacetyl primaquine (M-8506), 6-methoxy-5-trifluoroacetyl-8-(4-methyl-butyl-amino)-aminoquinoline oxalate, synthesized by the Institute of Parasitic Diseases was compared with primaquine for tissue schizontocidal action and acute ig LD50. In P yoelii sporozoite infected mice, the protection rates with ig M-8506 5, 10 and 20 mg (base)/kg on the day of infection were 56.7, 87.2 and 100%, respectively. These were comparable to the protection rates with primaquine 5, 10 and 20 mg(base)/kg (54.4, 90.8 and 100%, respectively). The radical curative effect was conducted in P cynomolgi sporozoite infected Macaca mulatta. Since im pyronaridine 10 mg/kg b.i.d. (6 h apart) completely eliminated the parasites in monkeys infected with erythrocytic stages of P cynomolgi, the tissue schizontocidal activities of M-8506 and primaquine were observed by im administration of pyronaridine 10 mg/kg b.i.d. on d 1. M-8506 at 0.75, 1.5 and 3 mg/(kg.d) x 3d plus pyronaridine were given to 7, 4 and 2 infected monkeys with parasitemia respectively. All the monkeys, except one receiving 0.75 mg/(kg.d) x 3 d, were radically cured. Primaquine 0.75, 1.5 and 3 mg/(kg.d) x 3 d were administered to 3, 3 and 2 monkeys respectively. Two monkeys receiving primaquine 0.75 mg/(kg.d) x 3 d relapsed on d 42. The parasitemia reappeared earlier than that treated with M-8506 0.75 mg/(kg.d) x 3 d and relapsed on d 62. Because M-8506 is less toxic than primaquine in mice and more effective in radical treatment of simian malaria, further studies on trifluoroacetyl primaquine are worthy to be considered.