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
| Autor: | Jacques H. Poupaert, Pierre Dumont, Michel Claesen, Aaron Garzon-Aburbeh |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Male
Reserpine Time Factors Dopamine Glyceride Administration Oral Pharmacology Levodopa Mice chemistry.chemical_compound Pharmacokinetics Drug Discovery Oxotremorine medicine Animals Phenylpropionates Chemistry Hydrolysis Brain Biological activity Haplorhini Prodrug Rats nervous system diseases Kinetics Molecular Medicine Triol Lymph medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 29:687-691 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00155a018 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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