Transport mechanism of an H1-antagonist at the blood-brain barrier: transport mechanism of mepyramine using the carotid injection technique.
The blood-brain barrier (BBB) permeability of mepyramine was measured by the carotid injection technique to elucidate the transport mechanism of an H1-antagonist in the central nervous system. Mepyramine was found to enter the brain by saturable and carrier-mediated transport. The in vivo kinetic parameters were estimated as follows: the maximum uptake rate (Jmax) was 7.12 +/- 1.37 mumol/min/g of brain, the Michaelis constant (Kt) was 4.40 +/- 2.00 mM, and the nonsaturable first order rate (Kd) was 0.28 +/- 0.02 ml/min/g of brain. The mepyramine transport was not inhibited either by nutrients or by choline, hemicholinium-3, though it was inhibited by the classical H1-antagonists such as diphenhydramine, diphenylpyraline, and also by propranolol. The above inhibitory effects suggest that a transport system different from the amine transport system exists for the BBB transport of mepyramine, and that this transporter is common not only for H1-antagonists but also for basic drugs.
Yamazaki
M
M
Research Department, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
Fukuoka
H
H
Nagata
O
O
Kato
H
H
Ito
Y
Y
Terasaki
T
T
Tsuji
A
A
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D017536:Carotid Artery, Common; D002794:Choline / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007269:Injections, Intra-Arterial; D008297:Male; D011738:Pyrilamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D006634:Histamine H1 Antagonists; D006426:Hemicholinium 3; D011738:Pyrilamine; D002794:Choline