The chemotherapy of rodent malaria, XXVI The potential value of WR 122,455 (a 9-phenanthrenemethanol) against drug-resistant malaria parasites

Abstract

The phenanthrenemethanol compound WR 122,455 is an effective blood schizontocide against lines of Plasmodium berghei that are highly resistant to primaquine, sulfonamides, pyrimethamine and cycloguanil. It is also active against the NS line that is moderately resistant to chloroquine. WR 122,455 is inactive against the RC line which is highly resistant to chloroquine. Resistance to WR 122,455 is fairly readily developed by the drug-sensitive N strain of P. berghei, using a relapse technique. Resistance develops very readily to the NS line of P. berghei. Both resistant lines exhibit cross-resistance to quinine, but a roughly normal response to chloroquine, primaquine, sulfonamides, dapsone, pyrimethamine and cylcoguanil. Resistance to WR 122,455 is stable through cyclical transmission, through cryopreservation and in the absence of drug selection pressure. The resistant parasites have an essentially normal morphology and virulence. A warning is given against the widescale use of WR 122,455 or similar new drugs for human malaria other than in a suitable combination, in order to minimize the danger of the development of resistance to them.