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

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.