A novel chemical delivery system for brain targeting.

Two different chemical approaches for brain drug delivery and targeting are proposed in the present review. One is a chemical drug delivery using a ring-closure reaction to the hydrophilic quaternary thiazolium compound in the brain. The other is a chemical drug targeting utilizing the nutrient receptor (transporter) system on the blood-brain barrier. The brain delivery system has been optimized and it was demonstrated that the brain delivery of three drugs, a drug for Parkinson's disease, an excitatory amino acid antagonist and a free radical scavenger, were improved by the conjugation with cis-2-formylaminoethenylthio derivatives in vivo. As for the brain targeting system, it was demonstrated that the conjugation with L-Glu improved the drug's brain distribution via the L-Glu excitatory and/or transport receptors in vitro and in vivo. These findings suggest that the concepts of two chemical approaches will contribute to the development of new central nervous system drugs.