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.
Original language | English |
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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 | |
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)