EFFECT OF FLUNARIZINE AND CALCIUM ON SEROTONIN UPTAKE IN HUMAN AND RAT-BLOOD PLATELETS AND RAT SYNAPTOSOMES

Calcium and the calcium overload blocker flunarizine exert profound ef fects on mood. We therefore studied the effect of calcium and flunariz ine on serotonin uptake in human and rat blood platelets and in rat sy naptosomes. Calcium (1.3 mmol/L) had a weak inhibiting effect on serot onin uptake in blood platelets, whereas no effect was observed in syna ptosomes. Flunarizine inhibited serotonin uptake in a concentration de pendent manner with an IC50 value of 1 mu mol/L in blood platelets and 5 mu mol/L in synaptosomes. The inhibition did not depend on the pres ence of extracellular calcium indicating that the effect is not couple d to a blockade of cellular calcium influx. In human blood platelets, the inhibition was of the noncompetitive type. These results indicate that flunarizine interacts directly with the 5-HT uptake site. The rel atively high concentration of flunarizine required to inhibit 5-HT upt ake may question the clinical importance of this effect.