The curative power of 4-(2:6-diaminopyrimidin-4-ylamino) phenylarsine oxide (compound 12,065) in infections of Trypanosoma rhodesiense in laboratory animals.

The toxicity to laboratory animals of 4-(2:6-diaminopyrimidin-4-ylamino)phenylarsine oxide (compound 12,065), and its ability to cure laboratory infections of Trypanosoma rhodesiense were investigated. The intramuscular LD50 to mice was 22 mg./kg.; rats were more susceptible. Monkeys tolerated two daily doses of 6 mg./kg., but not two daily doses of 10 mg./kg. The intramuscular CD50 to mice was about 6 mg./kg. with two strains of T. rhodesiense recently isolated from human patients, and 2 mg./kg. with a strain of T. rhodesiense which had been maintained by cyclical transmission through tsetse flies in the laboratory for about 17 months. These results are compared with those reported by Ainley and Davey (1958) for a strain of T. rhodesiense which had been maintained in the laboratory by cyclical transmission for about 12 years and then by syringe transmission for about 10 years. The syringe-transmitted strain was at least 20 times more susceptible to the drug than the recently isolated strains. The potencies of compound 12,065 and melarsen oxide/BAL in curing T. rhodesiense infections in mice were compared: the CD50 for compound 12,065 was 6.5 mg./kg. and for melarsen oxide/BAL was 3.7 mg./kg. The ratios LD50/CD50 for the drugs were about 4 and 6 respectively.