Av. Agasosler et al., Chorpromazine-induced increase in dipalmitoylphosphatidylserine surface area in monolayers at room temperature, BIOCH PHARM, 61(7), 2001, pp. 817-825
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.