The Effect of Flunarizine Treatment on Human Red Blood Cells

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Abstract
In a first group of experiments, control and ischemic blood was sampled from healthy male volunteers before and 3 hours after the administration of a single 40-mg oral dose of flunarizine or placebo. The blood samples were stored for 24 hours at 0°C to induce partial transformation of discocytes into echi nocytes (crenation). The effect of the drug on the degree of crenation was evaluated by scanning electron microscopy. In control blood, flunarizine treat ment significantly suppressed the discocyte-echinocyte transformation. Similar results were obtained with ischemic blood, although individual variability was greater. In a second group of experiments still in progress, control blood was taken from patients with intermittent claudication before and 24 hours after the first oral dose of flunarizine (4 × 20 mg) or placebo. The results again indicated that in patients flunarizine significantly reduced the echinocyte formation in stored blood samples. Based on the results of earlier studies it is postulated that flunarizine exerts its effect at the plasma membrane of the erythrocyte by inhibiting excessive influx of extracellular Ca2+. This mechanism of action, by which the compound suppresses echinocyte formation, may be similar to that by which it reduces hyperviscosity and possibly improves red blood cell (RBC) deformability.