Agasøsler A V, Tungodden L M, Cejka D, Bakstad E, Sydnes L K, Holmsen H
Department of Biochemistry and Molecular Biology, University of Bergen, Arstadveien 19, N-5009, Bergen, Norway.
Biochem Pharmacol. 2001 Apr 1;61(7):817-25. doi: 10.1016/s0006-2952(01)00542-1.
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.
朗缪尔技术表明，当亚相中存在微摩尔浓度的抗精神病药物氯丙嗪（CPZ）时，单层中酸性甘油磷脂（二棕榈酰磷脂酰丝氨酸、-甘油和二棕榈酰磷脂酸）的表面积会显著增加。中性甘油磷脂（二棕榈酰磷脂酰胆碱和-乙醇胺）的单层对CPZ没有显示出如此大的影响。与CPZ相比，毫摩尔浓度的单价阳离子Li+、K+、Na+、Rb+和Cs+似乎不会影响二棕榈酰磷脂酰丝氨酸单层，这表明单价阳离子两亲物CPZ的作用是由于其与脂质的酰基链相互作用。此外，150 mM的Na+可降低CPZ的作用，这表明钠离子可能会屏蔽带负电荷的头部基团，使其免受与带正电荷的药物分子的静电相互作用。还研究了两种CPZ类似物，氯丙嗪亚砜和侧链中有2个碳原子的CPZ。这些观察结果表明，CPZ的部分生物学效应，无论是抗精神病作用还是副作用，可能是由于CPZ对神经细胞膜中酸性甘油磷脂的作用。
