Effects of cetiedil on monovalent cation permeability in the erythrocyte: an explanation for the efficacy of cetiedil in the treatment of sickle cell anemia.

Abstract

Cetiedil, a drug reported to relieve painful crises in sickle cell anemia, has direct antisickling properties in vitro. However, neither oxygen affinity nor the solubility of deoxyhemoglobin S is altered by cetiedil. Due to the great influence the concentration of hemoglobin S has on the kinetics of gelation, we hypothesized that cetiedil might inhibit sickling by modifying erythrocyte Na+ or K+ movements in a manner which would prevent a rise in the concentration of intracellular hemoglobin. Cetiedil has two such effects: It causes a rise in passive Na+ movements and it inhibits a specific increase in K+ permeability secondary to a rise in cytoplasmic Ca2+ concentration. Cetiedil then may represent an alternate type of antisickling agent, exerting its effect through changes in erythrocyte membrane cation permeability rather than directly modifying hemoglobin S.

• Authors: L R Berkowitz, E P Orringer
• Journal: Blood cells (Blood Cells) Vol. 8 Issue 2 Pg. 283-8 ( 1982) ISSN: 0340-4684 [Print] United States
• PMID: 7159752 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antisickling Agents
• Azepines
• Cations, Monovalent
• cetiedil
• Sodium
• Oxygen

Topics

• Anemia, Sickle Cell (blood, drug therapy)
• Antisickling Agents (pharmacology, therapeutic use)
• Azepines (pharmacology, therapeutic use)
• Cations, Monovalent
• Cell Membrane Permeability (drug effects)
• Erythrocytes, Abnormal (metabolism)
• Humans
• Oxygen (blood)
• Sodium (blood)