Summary
To explore the molecular basis of the glycoside-quinidine interaction, the in vitro effect of quinidine on the binding of [3H]-ouabain and [3H]-digoxin to Na+ K+ ATPase receptors on human mononuclear cells was investigated. The maximum [3H]-ouabain binding capacity was 45.7±9.4×103 molecules/cell in pure lymphocyte preparations (n=8) and 75.5±7.3×103 molecules/cell in mixtures of mononuclear cells (n=8). These parameters were not influenced by 10−5 M quinidine. In eight equilibrium experiments with pure lymphocytes, the dissociation constant of [3H]-ouabain increased from 0.79±0.26×10−8 M in the absence of 10−5 M quinidine to 1.56±0.74×10−8 M in its presence (p<0.01), indicating that the affinity of the drug was decreased. Similar findings were observed using mixed mononuclear cells. In five uptake and release experiments, quinidine decreased the association rate constant of [3H]-ouabain from 3.15±0.36×104 M−1×s−1 to 2.01±0.37×104 M−1 s−1 (p<0.01), whereas the dissociation rate constant was not affected. A therapeutic concentration of quinidine does not affect the number of glycoside receptors on lymphocytes, but it does appear to reduce fractional receptor occupancy by both [3H]-ouabain and [3H]-digoxin at lower tracer concentrations. This finding is compatible with the clinical observation that quinidine reduces the distribution volume of digoxin.
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Pedersen, K.E., Klitgaard, N.A. Influence of quinidine on the binding of [3H]-ouabain and [3H]-digoxin by human lymphocytes. Eur J Clin Pharmacol 25, 263–270 (1983). https://doi.org/10.1007/BF00543801
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DOI: https://doi.org/10.1007/BF00543801