Open AccessIn vitro and in vivo potentiation of chloroquine against malaria parasites by an enantiomer of amlodipine
Author(s) -
Philippe Deloron,
Léonardo K. Basco,
Betty Lou Dubois,
C Gaudin,
F. Clavier,
J. Le Bras,
F. Verdier
Publication year - 1991
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.35.7.1338
Subject(s) - amlodipine , chloroquine , pharmacology , plasmodium falciparum , plasmodium yoelii , in vivo , calcium , calcium channel , calcium channel blocker , in vitro , enantiomer , chemistry , biology , malaria , medicine , immunology , biochemistry , endocrinology , parasitemia , microbiology and biotechnology , organic chemistry , blood pressure
A combination of chloroquine and amlodipine, a derivative of 1,4-dihydropyridine calcium channel blocker, was tested against Plasmodium falciparum in vitro and P. yoelii in mice. The dextrorotary enantiomer of amlodipine, practically devoid of calcium channel blocking action, increased chloroquine accumulation inside the infected mouse erythrocytes and potentiated chloroquine action against the resistant strains of P. falciparum in vitro and P. yoelii in mice. Unlike the racemate, the dextrorotary amlodipine was not toxic to the host animal, even at the highest dose of 250 mg/kg. No potentiating effect was noted in the chloroquine-susceptible strains of P. falciparum. The results of this study indicate that chloroquine potentiation of amlodipine is probably independent of calcium channels and that a combination therapy of the dextrorotary enantiomer of amlodipine and chloroquine might be a potentially useful therapeutic strategy against chloroquine-resistant falciparum malaria.