Some quantitative aspects of the binding of quinidine and related quinoline compounds by human serum albumin.

The interaction of quinidine with various body proteins may well be the fundamental process through which quinidine exerts its many effects. For example, quinidine binding with membrane lipoprotein may lead to decreased membrane permeability to passive ion movement. This permeability change has been held responsible for the quinidine-induced alterations in sodium and potassium exchange in cardiac muscle (1-4). Quinidine binding with critical enzyme proteins may be responsible for the alterations in intermediary metabolism which have been ascribed to quinidine (5). In our experience, glucose-6-phosphate dehydrogenase activity is reduced in vitro by quinidine. Finally, the known binding of quinidine to albumin may protect the cell against the action of quinidine by making less drug available at cellular sites. The nature of the interaction with protein of quinidine and of other compounds having a similar chemical structure seemed, therefore, to warrant an investigation. Albumin is readily available in adequate amounts and in relative purity. As noted above, it is known to complex with quinidine. Further, the state of the quinidine-albumin interaction might be considered as a prototype of the "protective" form and perhaps characteristic of all forms of quinidine binding to protein. For these reasons our initial investigations were concerned with the reactions of quinidine and related quinoline compounds with albumin. Experiments were designed to permit determination of the stoichiometry, the association constant, and the energies of binding for the reactions; and to show the contri-