Trypanocidal activity of a 5-substituted 2-nitroimidazole compound (Ro 15-0216) in mice

The trypanocidal activity of a 5-substituted 2-nitroimidazole compound (Ro 15-0216, 2-(dimethylamino)-4'-[(1-methyl-2-nitroimidazole-5-yl) methoxy] acetanilid) was tested in stocks of T.b. brucei, T.b. evansi, T. vivax, and T. congolense. The trypanosome stocks showed different sensitivities, the Trypanozoon group was most sensitive followed by T. vivax and T. congolense. Administration of the compound in the drinking water was superior to single intraperitoneal injections. A T.b. brucei stock with reduced sensitivity to Mel B and insensitive to diminazene aceturate was cured by a dose 13 times greater than that necessary for the drug-sensitive T.b. brucei stock, administered in the drinking water. Quinapyramine- and quinapyramine/suramin-resistant stocks of T.b. evansi were eliminated with doses of 63 and 160 mg/kg i.p., respectively; to eliminate the drug-sensitive T.b. brucei stock, 250 mg/kg i.p. were required. The combination of Ro 15-0216 with suramin showed a synergistic effect in suramin-sensitive and in suramin-resistant stocks of T.b. evansi, although high doses of suramin were applied in the latter. Synergism of Ro 15-0216 with diminazene aceturate was demonstrated in T. congolense-infected mice.