Effects of Phosphatidylserine and Phosphatidylethanolamine Content on Partitioning of Triflupromazine and Chlorpromazine between Phosphatidylcholine-Aminophospholipid Bilayer Vesicles and Water Studied by Second-Derivative Spectrophotometry

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概要

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• To assess the affinity of psychotropic phenothiazine drugs, triflupromazine (TFZ) and chlorpromazine (CPZ), for the membranes of central nervous system and the other organs in the body, the partition coefficients (K_ps) of these drugs to phosphatidylcholine (PC)-phosphatidylserine (PS) and PC-phosphatidylethanolamine (PE) small and large unilamellar vesicles (SUV, LUV) were examined by a second-derivative spectrophotometric method, since PS is abundantly contained in the membranes of the central nervous system and PE is distributed widely in the membranes of the organs in the body. Size and preparation methods of the vesicles did not affect the K_p values at each aminophospholipid content suggesting that the partition of the phenothiazine drugs was not affected by the structural differences in the vesicles such as their curvature or asymmetric distribution of the phospholipids between the outer and inner layers of the bilayer membranes. However, the K_p values of both drugs increased remarkably according to the PS content in the bilayer membranes, i. e., the K_p values for the vesicles of 30 mol% PS content were about 3 times of that for the vesicles of PC alone, while both K_p values slightly reduced with the increase in the content of PE in the bilayer membranes of PC-PE vesicles. The results indicate that both drugs have higher affinity for the PC-PS bilayer membranes than for the PC and PC-PE membranes, which can offer an evidence for the fact that TFZ and CPZ are predominantly distributed and accumulated in the brain and nerve cell membranes that contain PS abundantly.

• 2005-01-01

著者

• 北村 和則

  富山化学工業株式会社綜合研究所

• Ito Mika

  Kyoto Pharmaceutical University

• Kitamura Keisuke

  Kyoto Pharmaceutical University

• Nakagawa E

  Kyoto Pharmaceutical University

• Takashima M

  Kyoto Pharmaceutical University

• KITADE Tatsuya

  Kyoto Pharmaceutical University

• TAKEGAMI Shigehiko

  Kyoto Pharmaceutical University

• Kitamura K

  Kyoto Pharmaceutical University

• TAKASHIMA Miwa

  Kyoto Pharmaceutical University

• NAKAGAWA Eiko

  Kyoto Pharmaceutical University

• SONE Midori

  Kyoto Pharmaceutical University

• SUMITANI Rie

  Kyoto Pharmaceutical University

• YASUDA Yumiko

  Kyoto Pharmaceutical University

• 北村 和則

  Kyoto Pharmaceutical University

• Yasuda Y

  Kyoto Pharmaceutical University

• Kitamura Keisuke

  Kyoto College of Pharmacy

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