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

Masahiro Yamazaki; Tetsuya Terasaki; Kuniaki Yoshioka; Osamu Nagata; Hideo Kato; Yasuo Ito; Akira Tsuji

doi:10.1023/A:1018980914687

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

Masahiro Yamazaki, Tetsuya Terasaki, Kuniaki Yoshioka, Osamu Nagata, Hideo Kato, Yasuo Ito, Akira Tsuji

PHA - Life and Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

40 Citations (Scopus)

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 (K_i ) 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 (K_i) 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.

Original language	English
Pages (from-to)	1516-1518
Number of pages	3
Journal	Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Volume	11
Issue number	11
DOIs	https://doi.org/10.1023/A:1018980914687
Publication status	Published - 1994 Nov

Keywords

H-antagonist
blood-brain barrier (BBB)
common transport system
lipophilic basic drugs
propranolol

ASJC Scopus subject areas

Biotechnology
Molecular Medicine
Pharmacology
Pharmaceutical Science
Organic Chemistry
Pharmacology (medical)

Access to Document

10.1023/A:1018980914687

Cite this

Yamazaki, M., Terasaki, T., Yoshioka, K., Nagata, O., Kato, H., Ito, Y., & Tsuji, A. (1994). Carrier-Mediated Transport of H₁-Antagonist at the Blood-Brain Barrier: A Common Transport System of H₁-Antagonists and Lipophilic Basic Drugs. Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists, 11(11), 1516-1518. https://doi.org/10.1023/A:1018980914687

Carrier-Mediated Transport of H₁-Antagonist at the Blood-Brain Barrier : A Common Transport System of H₁-Antagonists and Lipophilic Basic Drugs. / Yamazaki, Masahiro; Terasaki, Tetsuya; Yoshioka, Kuniaki; Nagata, Osamu; Kato, Hideo; Ito, Yasuo; Tsuji, Akira.

In: Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists, Vol. 11, No. 11, 11.1994, p. 1516-1518.

Research output: Contribution to journal › Article › peer-review

Yamazaki, M, Terasaki, T, Yoshioka, K, Nagata, O, Kato, H, Ito, Y & Tsuji, A 1994, 'Carrier-Mediated Transport of H₁-Antagonist at the Blood-Brain Barrier: A Common Transport System of H₁-Antagonists and Lipophilic Basic Drugs', Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists, vol. 11, no. 11, pp. 1516-1518. https://doi.org/10.1023/A:1018980914687

Yamazaki M, Terasaki T, Yoshioka K, Nagata O, Kato H, Ito Y et al. Carrier-Mediated Transport of H₁-Antagonist at the Blood-Brain Barrier: A Common Transport System of H₁-Antagonists and Lipophilic Basic Drugs. Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists. 1994 Nov;11(11):1516-1518. https://doi.org/10.1023/A:1018980914687

Yamazaki, Masahiro ; Terasaki, Tetsuya ; Yoshioka, Kuniaki ; Nagata, Osamu ; Kato, Hideo ; Ito, Yasuo ; Tsuji, Akira. / Carrier-Mediated Transport of H₁-Antagonist at the Blood-Brain Barrier : A Common Transport System of H₁-Antagonists and Lipophilic Basic Drugs. In: Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists. 1994 ; Vol. 11, No. 11. pp. 1516-1518.

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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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