Transport Mechanism of an H1-Antagonist at the Blood-Brain Barrier: Transport Mechanism of Mepyramine Using the Carotid Injection Technique

Abstract

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 μmol/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. © 1994, The Pharmaceutical Society of Japan. All rights reserved.