Modulation of the function of human MDR1 P-glycoprotein by the antimalarial drug mefloquine

Biochem Pharmacol. 1996 Nov 22;52(10):1545-52. doi: 10.1016/s0006-2952(96)00556-4.


MDR1 P-glycoprotein in membranes of human tumor cells of the CEM/VBL100 line was selectively labelled using photoreactive analogs of verapamil, N-(p-azido-3-[125I]salicyl)amino-verapamil ([125I]ASA-V) and prazosin, 2-[4-(4-azido-3-[125I]iodobenzoyl)piperazin-1-yl]4 -amino-6,7-dimethoxyyquinazoline ([125I]ASA-P). Mefloquine, a quinolinemethanol antimalarial drug, was shown to inhibit the labelling of P-glycoprotein with an efficiency similar to that for verapamil, a known chemosensitizer. By contrast, chloroquine competed poorly for the binding site on P-glycoprotein. Mefloquine also inhibited the functional activity of P-glycoprotein. It decreased the rates of extrusion of [3H]vinblastine and the fluorescent dyes, fluo-3 acetomethoxy ester and rhodamine 123, from drug-resistant cells and decreased the level of resistance of these cells to vinblastine. The ability of mefloquine to inhibit P-glycoprotein function may be involved in the neurotoxic side-effects occasionally associated with the use of mefloquine as an antimalarial drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Affinity Labels
  • Antimalarials / pharmacology*
  • Binding Sites
  • Binding, Competitive
  • Biological Transport, Active / drug effects
  • Chloroquine / metabolism
  • Drug Interactions
  • Drug Resistance, Multiple
  • Fluorescent Dyes / metabolism
  • Humans
  • Kinetics
  • Mefloquine / pharmacology*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Prazosin / metabolism
  • Tumor Cells, Cultured
  • Verapamil / analogs & derivatives
  • Verapamil / metabolism
  • Verapamil / pharmacology
  • Vinblastine / metabolism
  • Vinblastine / toxicity


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Affinity Labels
  • Antimalarials
  • Fluorescent Dyes
  • Vinblastine
  • Chloroquine
  • Verapamil
  • Mefloquine
  • Prazosin