CARRIER-MEDIATED TRANSPORT OF H-1-ANTAGONIST AT THE BLOOD-BRAIN-BARRIER - A COMMON TRANSPORT-SYSTEM OF H-1-ANTAGONISTS AND LIPOPHILIC BASICDRUGS

The blood-brain barrier (BBB) transport system for H-1-antagonists was studied using primary cultured bovine brain capillary endothelial cel ls (BCEC). The uptake of [H-3]mepyramine was inhibited by various H-1- antagonists. Ketotifen competitively inhibited [H-3]mepyramine uptake with an inhibition constant (K-i) of 46.8 mu M. Lipophilic basic drugs such as propranolol, lidocaine and imipramine significantly inhibited [H-3]mepyramine uptake. In particular, propranolol inhibited [H-3]mep yramine uptake competitively at an inhibition constant (K-i) of 51.1 m u M. Moreover, in ATP-depleted BCEC, [H-3]mepyramine uptake was stimul ated by preloading with H-1-antagonists and lipophilic basic drugs. Th ese results indicated that H-1-antagonists are transported across the BBB via a carrier-mediated transport system common to lipophilic basic drugs.