Background: The capillary endothelial cells of the blood-brain barrier express an array of uptake and efflux drug transporters. Regulated expression and function of these transporters govern the central nervous system (CNS) penetration of essential nutrients, therapeutic drugs and, in some cases, toxins. Emerging evidence supports the notion of interplay between uptake and efflux drug transport as the determinants that define the extent of exposure of many drugs and their CNS action.
Objective: In this brief report, we review a number of key drug transporters known to be expressed at the blood-brain barrier and/or choroid plexus and focus on the implications of such transporters to CNS drug activity, side effects, andtoxicity. Specifically, this report focuses on the uptake transporters OATP1A2 (organic anion-transporting polypeptide 1A2) and MCT1 (monocarboxylate transporter 1), which are known to have substrates that are either neuroactive or known to result in CNS side effects and/or toxicity. Furthermore, the efflux transporters P-gp (P-gp; MDR1/ABCB1), BCRP (breast-cancer-resistance protein), OAT3 (organic anion transporter 3), and MRP4 (multidrug-resistance-associated protein 4) are also reviewed.