Effects of Inorganic Ions on the Binding of Triflupromazine and Chlorpromazine to Bovine Serum Albumin Studied by Spectrometric Methods
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概要
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The effects of inorganic salts, NaCl, NaBr, Nal, Na_2SO_4, KCl, KBr, KI, on the binding constants (Ks) of psychotropic phenothiazine drugs, triflupromazine (TFZ) and chlorpromazine, to bovine serum albumin (BSA) were examined by using second-derivative spectrophotometry. All of the salts examined, with the exception of Na_2SO_4, decreased the K values significantly, depending on the concentration of the salt, e.g., the decrease in the K values of both drugs were about 40% for 0.1M NaCl. The results obtained with Na_2SO_4 indicated that neither Na^+ nor SO^<2->_4 had any affect on the binding of the phenothiazines to BSA. Based on the Na_2SO_4 results and the finding that the effect of each potassium salt on binding was quite similar to that of the corresponding sodium salt, the effects of these halogen salts can be considered to be derived from their anions, although the phenothiazines are positively charged at pH 7.4. The effectiveness of the anions was determined to occur in the following order: I^-≫Br^->Cl^-; these results coincided with the published order of the binding affinity of these anions to albumin. The ^<19>F-NMR spectra of TFZ in the presence of each of these halogen salts revealed a concentration-dependent decrease in the intensity of the signal at 13.8ppm that had previously been assigned to the TFZ bound to Site II. Consequently, the effects of these anions on the binding of positively charged phenothiazine drugs are thought to be local steric effects caused by the binding of these anions to Site II.
- 公益社団法人日本薬学会の論文
- 2006-07-01
著者
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北村 和則
富山化学工業株式会社綜合研究所
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Kitamura Keisuke
Kyoto Pharmaceutical University
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Tanaka Rumi
Kyoto Pharmaceutical University
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KITADE Tatsuya
Kyoto Pharmaceutical University
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TAKEGAMI Shigehiko
Kyoto Pharmaceutical University
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Kitamura K
Kyoto Pharmaceutical University
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NAGATA Chieyo
Kyoto Pharmaceutical University
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OMRAN Ahmed
Kyoto Pharmaceutical University
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KAMIJIMA Yoshiko
Kyoto Pharmaceutical University
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北村 和則
Kyoto Pharmaceutical University
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Kitamura Keisuke
Kyoto College of Pharmacy
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