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The Effects of Flunarizine, a New Calcium Antagonist, on Human Red Blood Cells in vitro

Department of Biochemical Research, Ortho Pharmaceutical Corporation, Raritan, New Jersey

Francis J. Persico

Department of Biochemical Research, Ortho Pharmaceutical Corporation, Raritan, New Jersey

Karen Carpenter

Department of Biochemical Research, Ortho Pharmaceutical Corporation, Raritan, New Jersey

Mark Chasin

Department of Biochemical Research, Ortho Pharmaceutical Corporation, Raritan, New Jersey

It has been postulated that flunarizine's ability to increase tissue perfusion may be due to either antivasoconstrictor activity, or its effects on red blood cell deformability, or both. In studies reported here, the ability of flunarizine to in fluence human red blood cell membranes has been demonstrated in a number of systems:

(1) Calcium accumulation in the red blood cell is related to a loss of defor mability ; flunarizine inhibited ⁴⁵Ca accumulation in red blood cells with an IC50 of 46 ± 7 µM. (2) Flunarizine caused a significant increase in deformabi lity, as measured by its ability to decrease ischemia-induced hyperviscosity. (3) Flunarizine had the ability to prevent the discoid-echinocyte transformation in duced by metabolic depletion in ischemic blood as a result of storage. These al terations in red blood cells can all be explained by the localization of one site of action of flunarizine in the membrane of red blood cells, resulting in an inhibi tion of calcium accumulation and maintenance of normal red blood cell defor mability.

Angiology, Vol. 31, No. 5, 320-330 (1980)
DOI: 10.1177/000331978003100503


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