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Contribution of Monoamine Oxidase(MAO) to the Binding of Tertiary Basic Drugs in Isolated Perfused Rat Lung |
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| Authors: | Yoshida Hisahiro Okumura Katsuhiko Hori Ryohei |
| Affiliation: | (1) Department of Transfusion Medicine, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, 606, Japan;(2) Department of Hospital Pharmacy, School of Medicine, Kobe University, Kusunoki-cho, Chuo-ku, Kobe, 650, Japan;(3) Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, 606, Japan |
| Abstract: | The effect of tertiary basic drugs on mitochondrial MAO activity and the effect of MAO inhibitors (MAOIs) on basic drug accumulation in the isolated perfused rat lung were studied to clarify the role of MAO in drug binding to lung tissue. In the perfused lung preparation, the inhibition of MAO by basic drugs correlated well with their lipid solubilities and followed competitive kinetics. The inhibitory rank order (imipramine  diphenhydramine > quinine > metoclopramide > procainamide) also correlated with their accumulation in the perfused lung. Moreover, MAOI treatment decreased the accumulation of basic drugs in the lung, and the potency of MAOIs to inhibit drug accumulation in the lung correlated with their MAO inhibitory activity. These results indicate that lung MAO has specific binding sites for basic drugs and may function as a drug reservoir. |
| Keywords: | tertiary basic drug lung mitochondria monoamine oxidase(MAO) lipid solubility binding site isolated perfused lung |
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