Chorpromazine-induced increase in dipalmitoylphosphatidylserine surface area in monolayers at room temperature

Citation
Av. Agasosler et al., Chorpromazine-induced increase in dipalmitoylphosphatidylserine surface area in monolayers at room temperature, BIOCH PHARM, 61(7), 2001, pp. 817-825
Citations number
43
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
00062952 → ACNP
Volume
61
Issue
7
Year of publication
2001
Pages
817 - 825
Database
ISI
SICI code
0006-2952(20010401)61:7<817:CIIDSA>2.0.ZU;2-T
Abstract
The Langmuir technique revealed that the surface area of acidic glycerophos pholipids (dipalmitoylphosphatidylserine, -glycerol, and dipalmitoylphospha tidic acid) in monolayers increased dramatically when micromolar concentrat ions of the antipsychotic drug chlorpromazine (CPZ) were present in the sub phase. Monolayers of neutral glycerophospholipids (dipalmitoylphosphatidylc holine and -ethanolamine) did not show such a large effect with CPZ. Compar ed to CPZ, millimolar concentrations of the monovalent cations Li+, K+, Na, Rb+, and Cs' did not appear to influence the dipalmitoylphosphatidylserin e monolayer, suggesting that the effect of CPZ, a monovalent cationic ampho phile, was due to an interaction with the acyl chains of the lipids. In add ition, the effect of CPZ was reduced by 150 mM Na+, suggesting that the sod ium cations might screen the negatively charged headgroups from an electros tatic interaction with the positively charged drug molecule. Two CPZ analog s, chlorpromazine sulfoxide and CPZ with 2 carbons in the side chain, were also studied. These observations suggest that part of the biological effect s of CPZ, being antipsychotic and/or side effects, may be due to CPZ's acti on on the acidic glycerophospholipids in nerve cell membranes. (C) 2001 Els evier Science Inc. All rights reserved.