Chlorpromazine-induced increase in dipalmitoylphosphatidylserine surface area in monolayers at room temperature.
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.
Department of Biochemistry and Molecular Biology, University of Bergen, Arstadveien 19, N-5009, Bergen, Norway. armelle.varnier@pki.uib.no
A V
AV
Agasøsler
L M
LM
Tungodden
D
D
Cejka
E
E
Bakstad
L K
LK
Sydnes
H
H
Holmsen
D000731:Androstanes / Q000737:chemistry; D000838:Anions / Q000737:chemistry; D014150:Antipsychotic Agents / Q000737:chemistry; D002414:Cations, Monovalent / Q000737:chemistry; D002746:Chlorpromazine / Q000737:chemistry*; D004347:Drug Interactions; D020404:Glycerophospholipids / Q000737:chemistry; D009994:Osmolar Concentration; D010718:Phosphatidylserines / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry
C415601:3-oxo-androstan-17-yl-(2'',2'',6'',6''-tetramethyl-N-oxyl)piperidyl butan-1',4'-dioate; D000731:Androstanes; D000838:Anions; D014150:Antipsychotic Agents; D002414:Cations, Monovalent; D020404:Glycerophospholipids; D010718:Phosphatidylserines; C038694:dipalmitoylphosphatidylserine; D012965:Sodium Chloride; D002746:Chlorpromazine