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  • Title: Chlorpromazine-induced increase in dipalmitoylphosphatidylserine surface area in monolayers at room temperature.
    Author: Agasøsler AV, Tungodden LM, Cejka D, Bakstad E, Sydnes LK, Holmsen H.
    Journal: Biochem Pharmacol; 2001 Apr 01; 61(7):817-25. PubMed ID: 11274967.
    Abstract:
    The Langmuir technique revealed that the surface area of acidic glycerophospholipids (dipalmitoylphosphatidylserine, -glycerol, and dipalmitoylphosphatidic acid) in monolayers increased dramatically when micromolar concentrations of the antipsychotic drug chlorpromazine (CPZ) were present in the subphase. Monolayers of neutral glycerophospholipids (dipalmitoylphosphatidylcholine and -ethanolamine) did not show such a large effect with CPZ. Compared to CPZ, millimolar concentrations of the monovalent cations Li+, K+, Na+, Rb+, and Cs+ did not appear to influence the dipalmitoylphosphatidylserine monolayer, suggesting that the effect of CPZ, a monovalent cationic amphophile, was due to an interaction with the acyl chains of the lipids. In addition, the effect of CPZ was reduced by 150 mM Na+, suggesting that the sodium cations might screen the negatively charged headgroups from an electrostatic interaction with the positively charged drug molecule. Two CPZ analogs, chlorpromazine sulfoxide and CPZ with 2 carbons in the side chain, were also studied. These observations suggest that part of the biological effects of CPZ, being antipsychotic and/or side effects, may be due to CPZ's action on the acidic glycerophospholipids in nerve cell membranes.
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