“…Several influx and efflux transporters, including P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), monocarboxylic acid transporter, and organic cation transporter, have been identified in BCECs (Tamai and Tsuji, 2000b), and the differential CNS side effects among H1-antagonists may be associated with differences of BBB permeability via these transporters. Recently, it was reported that some nonsedative second-generation H1-antagonists are substrates of P-gp, and the involvement of P-gp in efflux transport at the BBB may explain their limited brain distributions (Cvetkovic et al, 1999;Tamai et al, 2000a;Chishty et al, 2001;Chen et al, 2003). Furthermore mepyramine, a classical sedative H1-antagonist, is taken up by the BCECs via a carrier-mediated transport system (Yamazaki et al, 1994a,b,c;Tamai et al, 2000a).…”