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 effects on mood. We therefore studied the effect of calcium and flunarizine on serotonin uptake in human and rat blood platelets and in rat synaptosomes. Calcium (1.3 mmol/L) had a weak inhibiting effect on serotonin uptake in blood platelets, whereas no effect was observed in synaptosomes. Flunarizine inhibited serotonin uptake in a concentration dependent manner with an IC50 value of 1 mumol/L in blood platelets and 5 mumol/L in synaptosomes. The inhibition did not depend on the presence of extracellular calcium indicating that the effect is not coupled 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 relatively high concentration of flunarizine required to inhibit 5-HT uptake may question the clinical importance of this effect.