TRANSPORT MECHANISM OF AN H-1-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 mechanis m of an H-1-antagonist in the central nervous system. Mepyramine was f ound to enter the brain by saturable and carrier-mediated transport. T he in vivo kinetic parameters were estimated as follows: the maximum u ptake rate (J(max)) was 7.12 +/- 1.37 mumol/min/g of brain, the Michae lis constant (K(t)) was 4.40 +/- 2.00 mM, and the nonsaturable first o rder rate (K(d)) was 0.28 +/- 0.02 ml/min/g of brain. The mepyramine t ransport was not inhibited either by nutrients or by choline, hemichol inium-3, though it was inhibited by the classical H-1-antagonists such as diphenhydramine, diphenylpyraline, and also by propranolol. The ab ove 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 H-1-antagonists but also for basic drugs.