| Synthesis and in vitro studies on a potential dopamine prodrug. | |
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MedLine Citation:
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PMID: 18972830 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of blood-brain barrier (BBB) which is a selective interface that excludes most water-soluble molecules from entering the brain. Neutral amino acids permeate the BBB by specific transport systems. Condensation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. The synthesis and characterization of the dopamine derivative 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (7) is described. The chemical and enzymatic stability of 7 was evaluated. The molecular weight (300 Da) and Log Papp (0.76) indicated that the physico-chemical characteristics of compound 7 are adequate to cross biological membranes. Compound 7 was enzymatically cleaved to free dopamine in rat brain homogenate (t1/2 = 460 min). In human plasma, the t1/2 of 7 was estimated comparable to that reported for L-DOPA. In view of a possible oral administration of 7, studies of its chemical behavior under conditions simulating those of the gastrointestinal tract showed that no dopamine production occurred; furthermore, 7 is able to permeate through a simulated intestinal mucosal membrane. The collected data suggest that compound 7 could beconsidered a very valuable candidate for subsequent in vivo evaluation. |
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Authors:
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L I Giannola; V De Caro; G Giandalia; M G Siragusa; L Lamartina |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Die Pharmazie Volume: 63 ISSN: 0031-7144 ISO Abbreviation: Pharmazie Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-31 Completed Date: 2008-12-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9800766 Medline TA: Pharmazie Country: Germany |
Other Details:
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Languages: eng Pagination: 704-10 Citation Subset: IM |
Affiliation:
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Dipartimento di Chimica e Tecnologie Farmaceutiche, Università di Palermo, Via Archirafi, 32, 90123 Palermo, Italy. litagian@unipa.it |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Buffers Chemistry, Physical Dopamine / administration & dosage*, pharmacology* Drug Delivery Systems Humans Indicators and Reagents Intestinal Mucosa / metabolism Magnetic Resonance Spectroscopy Membranes, Artificial Prodrugs / chemical synthesis*, pharmacology* Rats Rats, Sprague-Dawley Solubility |
| Chemical | |
Reg. No./Substance:
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0/Buffers; 0/Indicators and Reagents; 0/Membranes, Artificial; 0/Prodrugs |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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