The Screening and Evaluation of Experimental Antiparasitic Drugs

Abstract

Abstract : The investigation included three antimalarial screens, two African trypanosome screens, and an American trypanosome screen. Three antimalarial screens were; a primary blood schizonticidal test using Plasmodium berghei, a primary causal prophylactic test using Plasmodium voelii and Anopheles stephensi mosquitoes, and a secondary drug screening system using both of the above species of rodent malaria. The two African trypanosome systems included a primary screen and a secondary drug-resistant screen. The American trypanosome system was a primary one. In the primary antimalarial blood schizonticidal test 1, 425 dose-level tests were done with 320 exhibiting activity. In the prophylactic antimalarial test 756 three dose-level tests were performed to detect activity against sporozoites and/or exoerythrocytic stages. 80 compounds were active. In the regular secondary 8 compounds were tested against the drug-sensitive P-line of P. berghei, while 12 compounds were tested against the drug mefloquine resistant-line. Other special tests included, (1) Determining how stable the drug-resistant lines would be when drug pressure is removed, (2) How stable drug resistance is when drug-resistant parasites are mixed with drug-sensitive parasites, (3) The development of mefloquine and Fansidar resistance when mixed together, (4) The activity of silver sulfonamide and its non-silver analog against malaria and African and American trypanosomes, (5) Testing a new prophylactic antimalarial test system using exoerythrocytic schizonts transfered from rat liver to mouse peritoneal activity.