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Antimalarial activities of WR-194,965, an alpha-amino-o-cresol derivative.

Pilot appraisals of the activities of WR-194,965 and WR-204,165, two closely related o-cresol derivatives (both Mannich bases), in owl monkeys infected with the multidrug-resistant Vietnam Smith strain of Plasmodium falciparum showed that these compounds had similar levels of efficacy. Total course doses effecting 90% cures (CD(90)s) were 27 and 37 mg/kg of body weight for the respective compounds, values almost identical to the CD(90) of mefloquine (a highly promising 4-quinolinemethanol) against infections with the same strain, and the CD(90)s of chloroquine against infections with 4-aminoquinoline-susceptible strains. Expanded studies of the activities of WR-194,965 against infections with the Smith strain of P. falciparum and Vietnam Palo Alto strain of P. vivax, designed to guide projected evaluations in human volunteers, showed: (i) that the activity of this compound was a function of total dose administered, with single doses as effective as the same amount delivered in three or seven successive daily fractions; (ii) that all regimens effected rapid clearance of parasitemia; and (iii) that based on CD(90)s, this agent was twice as active against infections with the Palo Alto strain of P. vivax as against the Smith strain of P. falciparum. These findings, together with results of preclinical pharmacological studies pursued elsewhere, provided support for studies in human volunteers now underway.