A lymphotropic prodrug of L-dopa: synthesis, pharmacological properties and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propanoyl]propane-1,2,3-triol

Journal of Medicinal Chemistry
1986.0

Abstract

A glyceride derivative of L-Dopa, 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propan oyl] propane-1,2,3-triol (1), was synthesized and tested as an orally administrable prodrug endowed with lymphotropic properties. In the oxotremorine and reserpine tests, 1 exhibited an anti-Parkinsonian activity of longer duration than L-Dopa. The time course of concentration of 1 in the intestinal lymph of rat was determined and compared to that of L-Dopa. The results clearly demonstrate that 1 is selectively absorbed from the intestinal tract by the lymphatic route without any chemical or enzymatic degradation. In the blood of rats and mice, 1 functions as a prodrug to release L-Dopa by hydrolysis. In comparison with L-Dopa itself, higher L-Dopa levels for a longer period of time were observed as well as much more favorable L-Dopa/dopamine ratios. Ultimately, studies using mice show that the administration of 1 brings about a prolonged increase of L-Dopa and dopamine levels in the brain, without initial transient peak in concentration observed after an equimolecular dose of L-Dopa.

Knowledge Graph

Similar Paper

A lymphotropic prodrug of L-dopa: synthesis, pharmacological properties and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propanoyl]propane-1,2,3-triol
Journal of Medicinal Chemistry 1986.0
Synthesis and pharmacological activities of a novel tripeptide mimetic dopamine prodrug
Bioorganic & Medicinal Chemistry Letters 1995.0
Design, synthesis and biological evaluation of l-dopa amide derivatives as potential prodrugs for the treatment of Parkinson’s disease
European Journal of Medicinal Chemistry 2010.0
Design, synthesis, and preliminary pharmacological evaluation of new imidazolinones as l-DOPA prodrugs
Bioorganic & Medicinal Chemistry 2010.0
Study of the structural requirements for Dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide
Journal of Medicinal Chemistry 1978.0
Codrugs Linking <scp>l</scp>-Dopa and Sulfur-Containing Antioxidants: New Pharmacological Tools against Parkinson’s Disease
Journal of Medicinal Chemistry 2009.0
Synthesis and Study of<scp>l</scp>-Dopa−Glutathione Codrugs as New Anti-Parkinson Agents with Free Radical Scavenging Properties
Journal of Medicinal Chemistry 2007.0
Improved brain delivery of AZT using a glycosyl phosphotriester prodrug
Journal of Medicinal Chemistry 1992.0
Synthesis and biological evaluation of analogs of Pro-Leu-Gly-NH2 modified at the leucyl residue
Journal of Medicinal Chemistry 1990.0
Synthesis and dopamine receptor modulating activity of unsubstituted and substituted triproline analogues of l-prolyl-l-leucyl-glycinamide (PLG)
Bioorganic &amp; Medicinal Chemistry Letters 1999.0