PMID- 8112502 OWN - NLM STAT- MEDLINE DCOM- 19940331 LR - 20190825 IS - 0306-3623 (Print) IS - 0306-3623 (Linking) VI - 24 IP - 6 DP - 1993 Nov TI - Dose-dependent red blood cell volume increase induced by bepridil. PG - 1323-9 AB - 1. Bepiridil, (beta-[(2-methylpropoxy)methyl]-N-phenyl-N-(phenyl-methyl)-1-py rro lidine-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. Bepridil induces dose-dependent osmotic swelling of RBC and a concomitant decrease in mean corpuscular hemoglobin concentration (MCHC). 3. Modest decreases in MCHC greatly lengthen the delay time for polymerization of deoxygenated sickle hemoglobin (Hb S) and inhibit RBC sickling. 4. Equilibrium dialysis studies of bepridil and purified hemoglobin showed a low binding affinity (Kb = 10(3)/M). 5. The partition coefficient (Kp) determined for the interaction of RBC and bepridil was 1-3 x 10(3), which is similar to the Kp determined for other amphipathic molecules, such as chlorpromazine. FAU - Reilly, M P AU - Reilly MP AD - Division of Hematology, Children's Hospital of Philadelphia, PA 19104. FAU - Horiuchi, K AU - Horiuchi K FAU - Asakura, T AU - Asakura T LA - eng GR - HL-44640/HL/NHLBI NIH HHS/United States GR - P60 HL-38632/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Gen Pharmacol JT - General pharmacology JID - 7602417 RN - 0 (Hemoglobin, Sickle) RN - 0 (Hemoglobins) RN - 755BO701MA (Bepridil) SB - IM MH - Anemia, Sickle Cell/blood MH - Bepridil/blood/pharmacokinetics/*pharmacology MH - Dialysis MH - Dose-Response Relationship, Drug MH - Erythrocyte Membrane/drug effects MH - Erythrocyte Volume/*drug effects MH - Erythrocytes/metabolism MH - Hemoglobin, Sickle/metabolism MH - Hemoglobins/metabolism MH - Hemolysis/drug effects MH - Humans MH - Image Processing, Computer-Assisted MH - In Vitro Techniques MH - Solubility MH - Stimulation, Chemical EDAT- 1993/11/01 00:00 MHDA- 1993/11/01 00:01 CRDT- 1993/11/01 00:00 PHST- 1993/11/01 00:00 [pubmed] PHST- 1993/11/01 00:01 [medline] PHST- 1993/11/01 00:00 [entrez] AID - 0306-3623(93)90414-S [pii] AID - 10.1016/0306-3623(93)90414-s [doi] PST - ppublish SO - Gen Pharmacol. 1993 Nov;24(6):1323-9. doi: 10.1016/0306-3623(93)90414-s.