Influx transporters and drug targeting: Application of peptide and cation transporters

There are carrier-mediated mechanisms at the blood-brain barrier (BBB) for the permeation of drugs and natural compounds in the blood-to-brain and brain-to-blood directions. Organic cation/carnitine transporters, OCTN1 and OCTN2, are expressed at the BBB. OCTN1 transports some organic cations such as tetraethylammonium, quinidine, mepyramine in a Na+ independent manner. This review focuses on the role of transport systems in the uptake of xenobiotics, especially cationic and peptide drugs, across the BBB into the brain, as well as on strategies to increase drug delivery into the brain by blocking efflux transport protein function, or to reduce CNS side effects by modulating BBB transport processes.