Imipramine binding site. Temperature dependence of the binding of 3H-labeled imipramine and 3H-labeled paroxetine to human platelet membrane.

The characteristics of 3H-labeled imipramine and 3H-labeled paroxetine binding to human platelet membranes were determined at various temperatures between 0 and 37 degrees C. Both paroxetine and imipramine probably bind to the same molecular complex in the platelet membrane, but the binding characteristics are different for the two molecules. The dissociation constant (Kd) for imipramine increases from 0.3 nM to 7.0 nM with increasing incubation temperature in a continuous way, whereas Kd for paroxetine is almost constant, about 0.05 nM, between 0 and 19 degrees C, and first begins to increase from 0.06 nM to 0.16 nM between 20 and 37 degrees C. This suggests that the binding of paroxetine to the binding site induces a conformational change in the molecular complex of the binding site, whereas the binding of imipramine takes place without conformational changes in the binding site.