The impact of charge on chlorpromazine interaction with lipid membranes
Abstract
Psychiatric disorders, such as schizophrenia, are treated with antipsychotics. One such molecule is chlorpromazine (CPZ) that mainly exerts its therapeutic effect via its antagonist activity on the dopamine D2 receptor. Due to its high lipophilicity, it can partition and accumulate in membranes, which can lead to a delayed full clinical effect, reached weeks after the beginning of treatment. CPZ's insertion in membranes impacts the bilayer's physicochemical properties, which can indirectly impact membrane-embedded receptors, such as the D2 receptor. To further delve into the potential role of phosphatidylserine (PS) in CPZ-membrane interaction and subsequent remodeling of membrane properties, we have investigated CPZ interactions with phosphatidylcholine bilayers, a common model zwitterionic lipid, in the absence and presence of 10% PS. The study provides a comprehensive overview of CPZ's preferential interaction with PS-containing membranes. Altogether, data from complementary techniques showed a higher affinity of CPZ for PS headgroups, enhanced PS-mediated penetration in the membrane, and higher drug retention within the anionic lipid bilayer compared with POPC alone. At high concentration, CPZ induced the formation of mixed micelles on the surface of the treated membranes.
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BibTeX
@article{gorse2026impact,
title = {{The impact of charge on chlorpromazine interaction with lipid membranes}},
author = {Ana Gorse and Nicolò Paracini and Marion Mathelié-Guinlet and Victoria Lublin and Nada Taib-Maamar and Andrea Valentina Lopez Castillo and Yann Fichou and Estelle Rascol and Isabel Alves},
journal = {Journal of Lipid Research},
year = {2026},
month = oct,
doi = {10.1016/j.jlr.2026.101035},
url = {https://hal.science/hal-05786458v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - The impact of charge on chlorpromazine interaction with lipid membranes
AU - Ana Gorse
AU - Nicolò Paracini
AU - Marion Mathelié-Guinlet
AU - Victoria Lublin
AU - Nada Taib-Maamar
AU - Andrea Valentina Lopez Castillo
AU - Yann Fichou
AU - Estelle Rascol
AU - Isabel Alves
PY - 2026
DA - 2026/10/08
JO - Journal of Lipid Research
DO - 10.1016/j.jlr.2026.101035
UR - https://hal.science/hal-05786458v1
AB - Psychiatric disorders, such as schizophrenia, are treated with antipsychotics. One such molecule is chlorpromazine (CPZ) that mainly exerts its therapeutic effect via its antagonist activity on the dopamine D2 receptor. Due to its high lipophilicity, it can partition and accumulate in membranes, which can lead to a delayed full clinical effect, reached weeks after the beginning of treatment. CPZ's insertion in membranes impacts the bilayer's physicochemical properties, which can indirectly impact membrane-embedded receptors, such as the D2 receptor. To further delve into the potential role of phosphatidylserine (PS) in CPZ-membrane interaction and subsequent remodeling of membrane properties, we have investigated CPZ interactions with phosphatidylcholine bilayers, a common model zwitterionic lipid, in the absence and presence of 10% PS. The study provides a comprehensive overview of CPZ's preferential interaction with PS-containing membranes. Altogether, data from complementary techniques showed a higher affinity of CPZ for PS headgroups, enhanced PS-mediated penetration in the membrane, and higher drug retention within the anionic lipid bilayer compared with POPC alone. At high concentration, CPZ induced the formation of mixed micelles on the surface of the treated membranes.
SN - 0022-2275
ER -