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Dose-dependent red blood cell volume increase induced by bepridil

Authors
Journal
General Pharmacology The Vascular System
0306-3623
Publisher
Elsevier
Publication Date
Volume
24
Issue
6
Identifiers
DOI: 10.1016/0306-3623(93)90414-s
Disciplines
  • Medicine

Abstract

Abstract 1. 1. Bepiridil, (β-[(2-methylpropoxy)methyl]-N-phenyl-N-(phenyl-methyl)-1-pyrrolidine-ethanamine), a calcium channel blocker, inhibits sickling of red blood cells (RBC) from patients with sickle cell disease (SCD) at micromolar concentrations in vitro. 2. 2. Bepridil induces dose-dependent osmotic swelling of RBC and a concomitant decrease in mean corpuscular hemoglobin concentration (MCHC). 3. 3. Modest decreases in MCHC greatly lengthen the delay time for polymerization of deoxygenated sickle hemoglobin (Hb S) and inhibit RBC sickling. 4. 4. Equilibrium dialysis studies of bepridil and purified hemoglobin showed a low binding affinity (K b = 10 3/M). 5. 5. The partition coefficient (K p) determined for the interaction of RBC and bepridil was 1−3 × 10 3, which is similar to the K p determined for other amphipathic molecules, such as chlorpromazine.

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