摘要：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±1.37μmol/min/g of brain, the Michaelis constant (Kd) was 4.40±2.00mM, and the nonsaturable first order rate (Kd) was 0.28±0.02ml/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.
关键词：H1-antagonist;blood-brain barrier;carrier-mediated transport;brain uptake index
