Chemotherapeutic Activity of Certain 8-Aminoquinolines, Particularly Pentaquine, in Experimental Chagas' Disease

Abstract

Nine 8-aminoquinolines were tested for activity against Trypanosoma cruzi in Swiss mice. In screening tests medication was begun 4 days after infection and consisted of 5 or 6 consecutive daily intraperit. injections of the drugs to be tested in doses approximating the intravenous LD50 for mice. SN 5535, SN 7672 and SN 11167 were inactive. SN 191, SN 971, SN 1491, SN 2026 and SN 10994 had slight activity. SN 13276 (pentaquine) showed significant activity at 30 mg./kg./day on the screening test. When this product was administered orally to infected mice 95% of the animals receiving 20 mg./kg./day for 18 days (total 360 mg./kg.) survived 60 days after infection when the survival in the infected unmedicated controls was only 20%. Treatment of dogs with pentaquine at 20 mg./kg./day for 4 days caused acute toxic symptoms and death. The demonstration of trypanocidal activity against T. cruzi among the 8-aminoquinolines is of interest from 3 aspects: (1) it shows a new para-siticidal attribute of this chemical group; (2) it reveals a new chemical group in which to seek compounds active against T. cruzi; (3) it introduces an agent for the treatment of experimental Chagas'' disease which is active on oral administration, all previously suggested compounds having been usable only parenterally.