Current views on the mechanisms of resistance to quinoline-containing drugs in Plasmodium falciparum.
The issue of chloroquine resistance in Plasmodium falciparum and cross-resistance patterns with other related chemotherapeutic agents has been the subject of intense interest for many years. Despite this level of investigation, the picture remains very unclear. Although it is accepted that chloroquine resistance is, at least in part, a function of reduced drug accumulation, the question of reduced drug uptake versus enhanced efflux is yet to be resolved at both the molecular and biochemical levels. Further, the absolute cross-resistance patterns of chloroquine-resistant isolates to closely related analogues is a matter for debate, although there appears to be a reciprocal arrangement between resistance to chloroquine and resistance to mefloquine, halofantrine and possibly quinine. Evidence is presented for the coexistence of two or more chloroquine-resistance mechanisms in isolates of P. falciparum, only one of which is verapamil sensitive. In addition, an analysis of cross-resistance patterns, as measured by the inoculum effect, is presented.
Ward
S A
SA
Department of Pharmacology and Therapeutics, University of Liverpool, U.K.
Bray
P G
PG
Mungthin
M
M
Hawley
S R
SR
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D001692:Biological Transport; D002738:Chloroquine / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D010616:Phenanthrenes / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D000962:Antimalarials; D010616:Phenanthrenes; D002738:Chloroquine; D014700:Verapamil; C023768:halofantrine