Plasmodium falciparum: modulation by calcium antagonists of resistance to chloroquine, desethylchloroquine, quinine, and quinidine in vitro.
Intrinsic interactions of calcium antagonists (broadly defined) and quinoline-containing antimalarial drugs were evaluated against chloroquine-sensitive and chloroquine-resistant clones of Plasmodium falciparum in vitro. Verapamil, D-600 (methoxyverapamil), Ro 11-2933/001 (tiapamil analogue), chlorpromazine, SKF 21133-A (chlorpromazine analogue), and diltiazem each potentiated the efficacy of the quinoline-containing antimalarials chloroquine, desethylchloroquine, and quinine with a chloroquine-resistant clone of P. falciparum, but did not affect the response of the quinoline-susceptible clone. Similar concentrations of either chlorpromazine or Ro 11-2933/001 lowered the IC50 of the resistant clone to approximately the same level as that observed for the sensitive clone for each of the quinolines tested. This reversal of resistance by many of the same calcium antagonists underscores the similarities in one mechanism of multi-drug resistance in neoplastic cells and quinoline-resistance in P. falciparum.
Kyle
D E
DE
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Oduola
A M
AM
Martin
S K
SK
Milhous
W K
WK
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002738:Chloroquine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D066298:In Vitro Techniques; D010963:Plasmodium falciparum / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D011804:Quinolines; D002738:Chloroquine; D011803:Quinine; D011802:Quinidine; C007278:desethylchloroquine