Impact of Nicotine Transport across the Blood–Brain Barrier: Carrier-Mediated Transport of Nicotine and Interaction with Central Nervous System Drugs

<p>Nicotine, an addictive substance, is absorbed from the lungs following inhalation of tobacco smoke, and distributed to various tissues such as liver, brain, and retina. Recent <i>in vivo</i> and <i>in vitro</i> studies suggest the involvement of a carrier-mediated transport process in nicotine transport in the lung, liver, and inner blood–retinal barrier. In addition, <i>in vivo</i> studies of influx and efflux transport of nicotine across the blood–brain barrier (BBB) revealed that blood-to-brain influx transport of nicotine is more dominant than brain-to-blood efflux transport of nicotine. Uptake studies in TR-BBB13 cells, which are an <i>in vitro</i> model cell line of the BBB, suggest the involvement of H⁺/organic cation antiporter, which is distinct from typical organic cation transporters, in nicotine transport at the BBB. Moreover, inhibition studies in TR-BBB13 cells showed that nicotine uptake was significantly reduced by central nervous system (CNS) drugs, such as antidepressants, anti-Alzheimer's disease drugs, and anti-Parkinson's disease drugs, suggesting that the nicotine transport system can recognize these molecules. The cumulative evidence would be helpful to improve our understanding of smoking-CNS drug interaction for providing appropriate medication.</p>