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Carrier-Mediated Transport of H1-Antagonist at the Blood-Brain Barrier: A Common Transport System of H1-Antagonists and Lipophilic Basic Drugs

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Abstract

The blood-brain barrier (BBB) transport system for H1 antagonists was studied using primary cultured bovine brain capillary endothelial cells (BCEC). The uptake of [3H]mepyramine was inhibited by various H1-antagonists. Ketotifen competitively inhibited [3H]mepyramine uptake with an inhibition constant (Ki ) of 46.8 µM. Lipophilic basic drugs such as propranolol, lidocaine and imipramine significantly inhibited [3H]mepyramine uptake. In particular, propranolol inhibited [3H]mepyramine uptake competitively at an inhibition constant (Ki) of 51.1 µM. Moreover, in ATP-depleted BCEC, [3H]mepyramine uptake was stimulated by preloading with H1- antagonists and lipophilic basic drugs. These results indicated that H1-antagonists are transported across the BBB via a carrier-mediated transport system common to lipophilic basic drugs.

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Author notes

  1. Tetsuya Terasaki

    Present address: Faculty of Pharmaceutical Sciences, University of Tokyo, Kongo, Bunkyo-ku, Tokyo, 113, Japan

Authors and Affiliations

  1. Research Department, Research and Development Division, Hokuriku Seiyaku Co., Ltd., Inokuchi, Katsuyama, Fukui, 911, Japan

    Masahiro Yamazaki, Osamu Nagata, Hideo Kato & Yasuo Ito

  2. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa, 920, Japan

    Tetsuya Terasaki, Kuniaki Yoshioka & Akira Tsuji

Authors
  1. Masahiro Yamazaki
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  2. Tetsuya Terasaki
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  3. Kuniaki Yoshioka
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  4. Osamu Nagata
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  5. Hideo Kato
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  6. Yasuo Ito
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  7. Akira Tsuji
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Yamazaki, M., Terasaki, T., Yoshioka, K. et al. Carrier-Mediated Transport of H1-Antagonist at the Blood-Brain Barrier: A Common Transport System of H1-Antagonists and Lipophilic Basic Drugs. Pharm Res 11, 1516–1518 (1994). https://doi.org/10.1023/A:1018980914687

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  • DOI: https://doi.org/10.1023/A:1018980914687

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