Inhibition of brain choline uptake by isoarecolone and lobeline derivatives: implications for potential vector-mediated brain drug delivery.

Delivery of certain compounds to brain is restricted by the nature of the blood-brain barrier (BBB). Many valuable pharmaceuticals are excluded from the CNS due to hydrophilicity or charge. These limitations have been overcome by numerous methods. One method we use is to take advantage of saturable nutrient transporters located at the barrier. These systems transport hydrophilic and charged nutrients into brain such as choline, a quaternized neurotransmitter precursor. Using knowledge of their substrate specificity, it is possible to deliver agents into brain using these nutrient carriers. In this report, derivatives of lobeline and isoarecolone were evaluated to determine if they may gain access to brain by the blood-brain barrier basic amine transporter using the in situ brain perfusion technique. These compounds do bind the blood-brain barrier basic amine transporter and may enter brain by this transport system.