In summary, the results suggest that carrier-mediated transport can be used to augment the brain delivery of a wide variety of hydrophilic therapeutic drugs. A large number of carriers are now known to be present at the brain capillary endothelium, and in many instances these carriers have been shown to mediate the brain uptake of exogenous drugs. The findings with D,L-NAM demonstrate that brain delivery can be improved through design of selective, high affinity agents. Although NAM was developed for the large neutral amino acid carrier, high affinity drugs could be produced for other systems, as shown by the work of Schein et al. with nitrogen mustard monosaccharides and by the work of Deves and Krupka on choline derivatives. Lastly, the method may allow some selectivity of delivery because of differential expression of transport carriers between tissues and in various disease states.