Carrier-mediated Transport of H1-antagonist at the Blood-brain Barrier: a Common Transport System of H1-antagonists and Lipophilic Basic Drugs

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 1994 Nov 1

PMID 7870663

Citations 5

Authors

M Yamazaki

T Terasaki

K Yoshioka

O Nagata

H Kato

Y Ito

A Tsuji

Affiliations

Soon will be listed here.

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 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.

Citing Articles

Proteomics-Based Transporter Identification by the PICK Method: Involvement of TM7SF3 and LHFPL6 in Proton-Coupled Organic Cation Antiport at the Blood-Brain Barrier.

Kurosawa T, Tega Y, Uchida Y, Higuchi K, Tabata H, Sumiyoshi T Pharmaceutics. 2022; 14(8).

PMID: 36015309 PMC: 9413594. DOI: 10.3390/pharmaceutics14081683.

Mechanism of brain targeting by dexibuprofen prodrugs modified with ethanolamine-related structures.

Li Y, Zhou Y, Jiang J, Wang X, Fu Y, Gong T J Cereb Blood Flow Metab. 2015; 35(12):1985-94.

PMID: 26154870 PMC: 4671119. DOI: 10.1038/jcbfm.2015.160.

Involvement of a novel organic cation transporter in verapamil transport across the inner blood-retinal barrier.

Kubo Y, Kusagawa Y, Tachikawa M, Akanuma S, Hosoya K Pharm Res. 2012; 30(3):847-56.

PMID: 23179781 DOI: 10.1007/s11095-012-0926-y.

Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development.

Ohtsuki S, Terasaki T Pharm Res. 2007; 24(9):1745-58.

PMID: 17619998 DOI: 10.1007/s11095-007-9374-5.

Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems.

Tsuji A NeuroRx. 2005; 2(1):54-62.

PMID: 15717057 PMC: 539320. DOI: 10.1602/neurorx.2.1.54.

References

Yamazaki M, Terasaki T, Yoshioka K, Nagata O, Kato H, Ito Y . Carrier-mediated transport of H1-antagonist at the blood-brain barrier: mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer cultures. Pharm Res. 1994; 11(7):975-8. DOI: 10.1023/a:1018923017954. View

Pardridge W, Sakiyama R, Fierer G . Blood-brain barrier transport and brain sequestration of propranolol and lidocaine. Am J Physiol. 1984; 247(3 Pt 2):R582-8. DOI: 10.1152/ajpregu.1984.247.3.R582. View

Kang Y, Terasaki T, Ohnishi T, Tsuji A . In vivo and in vitro evidence for a common carrier mediated transport of choline and basic drugs through the blood-brain barrier. J Pharmacobiodyn. 1990; 13(6):353-60. DOI: 10.1248/bpb1978.13.353. View

Kurihara A, Suzuki H, Sawada Y, Sugiyama Y, Iga T, Hanano M . Uptake of propranolol by microvessels isolated from bovine brain. J Pharm Sci. 1987; 76(10):759-64. DOI: 10.1002/jps.2600761002. View

Yamazaki M, Fukuoka H, Nagata O, Kato H, Ito Y, Terasaki T . Transport mechanism of an H1-antagonist at the blood-brain barrier: transport mechanism of mepyramine using the carotid injection technique. Biol Pharm Bull. 1994; 17(5):676-9. DOI: 10.1248/bpb.17.676. View