Improved delivery through biological membranes. 4. Prodrugs of L-DOPA

Various classes of transient derivatives of L-Dopa have been synthesized, systematically protecting one or more of the main sites of metabolism in the molecule: the carboxy function, the amino, and/or the catechol system. The derivatives studied include carboxy esters, phenol esters, amides, peptides, and various combinations of these functions. A number of these derivatives effectively prevent the metabolism of L-Dopa prior to and/or during the absorption process, resulting in a significantly better bioavailability of the drug. In vivo studies using dogs showed up to 2.5-fold increase in L-Dopa blood levels. The metabolism as well as toxicity aspects of the prodrugs is also discussed.