STEREOSELECTIVE ACCUMULATION OF THE BETA-RECEPTOR BLOCKING DRUG ATENOLOL BY HUMAN PLATELETS

We have studied the stereochemistry of accumulation of the hydrophilic beta-adrenoceptor antagonist rac-atenolol by human platelets in vitro. The accumulation was slow, not reaching equilibrium until 90 min at 37-degrees-C. The uptake was temperature dependent with the accumulation at 37-degrees-C being 3-4 times greater than at 4-degrees-C. The accumulation was also stereoselective at 37-degrees-C, favoring the active (-)-enantiomer over the (+)-enantiomer by 2.3-fold. Reserpine, but not desipramine, inhibited the platelet accumulation of rac-atenolol enantiospecifically. This uptake profile is different from the platelet uptake of lipophilic beta-blockers, which is characterized by nonspecific membrane binding, but similar to the carrier-mediated accumulation of the neurotransmitter norepinephrine by storage granules within the platelet.