Carrier-mediated transport of H1-antagonist at the blood-brain barrier: a common transport system of H1-antagonists and lipophilic basic drugs.
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 microM. 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 microM. 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.
Yamazaki
M
M
Research Department, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
Terasaki
T
T
Yoshioka
K
K
Nagata
O
O
Kato
H
H
Ito
Y
Y
Tsuji
A
A
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics*; D007099:Imipramine / Q000493:pharmacokinetics; D008012:Lidocaine / Q000493:pharmacokinetics; D011433:Propranolol / Q000493:pharmacokinetics; D011738:Pyrilamine / Q000493:pharmacokinetics*; D012995:Solubility
D002352:Carrier Proteins; D006634:Histamine H1 Antagonists; D008012:Lidocaine; D011433:Propranolol; D011738:Pyrilamine; D007099:Imipramine