Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium influx into sickle cells, with consequential activation of the Ca2(+)-activated K+ efflux (Gardos) channel, is a potential cause of cellular dehydration and loss of deformability. Bepridil, a recently described inhibitor of the Gardos channel, was found at pharmacological concentration (1 mumol/l) to inhibit significantly (P less than 0.01) the loss of deformability when sickle cells were subjected to cycles of oxygenation-deoxygenation for 15 h at 37 degrees C. Bepridil also inhibited significantly (P less than 0.005) the formation of irreversibly sickled cells. Drugs that preserve the K+ and therefore water content of erythrocytes are of potential value for hydrotherapy of sickle cell disease.
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PMID:Bepridil protects sickle cells against the adverse rheological effects of cyclical deoxygenation. 261 Nov 38

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.
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PMID:Dose-dependent red blood cell volume increase induced by bepridil. 811 2