Interaction of Antidepressant Drugs with Lipid Bilayers Studied by High-Resolution Carbon-13 (^<13>C-) and High-Power Deuterium Nuclear Magnetic Resonance (^2H-NMR) Spectroscopy : The Manner of Binding as Deduced from the Differential Line-Broadening of ^
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概要
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The manner of binding of imipramine (IMIP) and amitriptyline (AM) as well as chlorpromazine (CPZ) to single-or multi-bilayers of egg phosphatidylcholine (PC) was analyzed by carbon-13 (^<13>C-) and deuterium nuclear magnetic resonance (^2H-NMR) methods. For this purpose, we first tried to assign or re-assign the aromatic ^<13>C chemical shifts by the selective proton-decoupling method. We observed that the ^<13>C-NMR signals from a specific portion of the aromatic moiety of IMIP and AM are differently broadened as a result of binding to single bilayers of egg PC. In contrast, the signals of all carbons adjacent to protons in the aromatic moiety of CPZ were completely suppressed in the presence of egg PC. The observation of such differential linebroadening for IMIP and AM was interpreted in terms of the presence of anisotropic diffusion at the tricyclic moiety incorporated into the bilayers. However, drugs tightly bound to lipids such as CPZ cannot afford signals showing such differential line-broadening because of the slowed molecular motion in the bilayers. The extent of binding to lipids as viewed from the characteristic change of the ^<13>C-NMR signals is in parallel with that determined from binding experiments by centrifugation and equilibrium dialysis. The reason why the ^<13>C-NMR signals of IMIP and AM are visible even in the presence of lipid bilayers is considered to be the larger proportion of these drugs involved in fast exchange between lipids and the aqueous phase, on the basis of the observation of a major central peak in the ^2H-NMR spectra of [2,4,6,8-^2H_4] IMIP in the presence of multibilayers of egg PC. Nevertheless, there appears to be some portion of IMIP which penetrates deeply into the hydrophobic portion of egg PC and has a slow exchange rate compared with the inverse of the quadrupole splitting (16kHz).
- 社団法人日本薬学会の論文
- 1985-05-25
著者
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斉藤 肇
Biophysics Division National Cancer Center Research Institute
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斉藤 肇
Biophysics Divisions National Cancer Center Research Institute:(present Address)department Of Life S
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多部田 涼子
Biophysics Division National Cancer Center Research Institute
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MAHAJAN SUDHA
Biophysics Division National Cancer Center Research Institute
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前田 満和
Chemotherapy Division National Cancer Center Research Institute
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前田 満和
National Cancer Center Research Institute
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