| Hydrolysis and acyl migration of a catechol monoester of L-dopa: L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine. | |
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MedLine Citation:
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PMID: 2231333 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hydrolysis and acyl migration studies on L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine (1, NB-355), which produced long-lasting plasma L-dopa levels after oral dosing, have been conducted. Compound 1 exists as pure 4-O-pivaloyl-L-dopa in the solid state, but it converts rapidly to a mixture of the 3- and 4-O-isomers in solution. The rate of acyl migration increased with increases in pH and temperature, and the content of the 4-O-isomer in the equilibrium state was 53-59%. The hydrolysis rate of 1 to L-dopa (6) also increased with increases in pH and temperature, and accelerated steeply at neutral and alkaline pH. The rapid hydrolysis at neutral pH was not observed with O-pivaloyl-L-tyrosine (3), di-O-pivaloyl-L-dopa (4), or L-dopa methyl ester (5). Because of this chemical lability, 1 was hydrolyzed in rat plasma far faster than the other tested catechol esters. However, in rat intestinal homogenate at pH 6.0, 1 was hydrolyzed at the slowest rate among the tested esters, predominantly by a diisofluorophosphate (DFP)-sensitive esterase. Thus, 1 showed a unique in vitro profile on hydrolysis and acyl migration due to the existence of a neighboring hydroxyl group. The stability of 1 in the intestine might be essential for the long-lasting plasma L-dopa profile after oral dosing of 1. |
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Authors:
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M Ihara; S Nakajima; A Hisaka; Y Tsuchiya; Y Sakuma; H Suzuki; K Kitani; M Yano |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 79 ISSN: 0022-3549 ISO Abbreviation: J Pharm Sci Publication Date: 1990 Aug |
Date Detail:
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Created Date: 1990-12-06 Completed Date: 1990-12-06 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 703-8 Citation Subset: IM |
Affiliation:
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Central Research Laboratories, Banyu Pharmaceutical Company, Ltd., Tokyo, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acylation Animals Buffers Chemical Phenomena Chemistry Hydrogen-Ion Concentration Hydrolysis Intestines / metabolism Kinetics Levodopa / analogs & derivatives*, blood, metabolism* Magnetic Resonance Spectroscopy Male Pancreas / metabolism Rats Rats, Inbred Strains Solutions Temperature |
| Chemical | |
Reg. No./Substance:
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0/Buffers; 0/Levodopa; 0/Solutions; 122551-95-5/L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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