Open AccessAntimalarial Activities of WR-194,965, an α-Amino- o -Cresol Derivative
Author(s) -
L. H. Schmidt,
Ruth Crosby
Publication year - 1978
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.14.5.672
Subject(s) - chloroquine , mefloquine , parasitemia , plasmodium falciparum , strain (injury) , pharmacology , plasmodium vivax , quinine , malaria , biology , medicine , immunology
Pilot appraisals of the activities of WR-194,965 and WR-204,165, two closely relatedo -cresol derivatives (both Mannich bases), in owl monkeys infected with the multidrug-resistant Vietnam Smith strain ofPlasmodium falciparum showed that these compounds had similar levels of efficacy. Total course doses effecting 90% cures (CD90 s) were 27 and 37 mg/kg of body weight for the respective compounds, values almost identical to the CD90 of mefloquine (a highly promising 4-quinolinemethanol) against infections with the same strain, and the CD90 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 ofP. falciparum and Vietnam Palo Alto strain ofP. 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 CD90 s, this agent was twice as active against infections with the Palo Alto strain ofP. vivax as against the Smith strain ofP. falciparum . These findings, together with results of preclinical pharmacological studies pursued elsewhere, provided support for studies in human volunteers now underway.