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  • Title: Spin-label study of phenothiazine interactions with erythrocyte ghost membranes: a possible membrane-mediated antisickling action.
    Author: Jones GL, Woodbury DM.
    Journal: J Pharmacol Exp Ther; 1978 Oct; 207(1):203-11. PubMed ID: 702341.
    Abstract:
    Erythrocyte membrane alterations by 11 phenothiazine derivatives known to inhibit the sickling phenomenon in vitro have been evaluated in ghosts by the spin-labeling technique. Four sulfydryl-reactive spin labels were employed: 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl; 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl; 3-[(2-iodoacetamido)methyl]-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl; and 3-(maleimidomethyl)-2,2,5,5-tetramethyl-1-pyrrolidiny-loxyl. The latter spin label was judged most useful since its spectrum was sensitive to subtle perturbations by drugs spanning a considerable potency range. An increase in spin-probe immobilization was induced by each drug with approximate relative potencies given by the order: desmethylchlorpromazine congruent to thioridazine congruent to fluphenazine congruent to prochlorperazine congruent to trifluoperazine greater than acetophenazine congruent to triflupromazine congruent to chlorpromazine greater than promazine greater than promethazine greater than perphenazine. This order correlates (P less than .01) with their antisickling potency in vitro.
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