| A screening system of prodrugs selective for MAO-A or MAO-B. | |
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MedLine Citation:
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PMID: 14697904 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We synthesized several prodrugs of glycine and gamma-aminobutyric acid. In order to establish a screening system from the prodrugs of selective activity to MAO-A or MAO-B, we examined purification conditions such as solubilization with Triton X-100, precipitation with ammonium sulfate, gel filtration and anion exchange chromatography. MAO-B was purified from various tissues such as guinea pig brain, kidney and spleen. MAO-A from human placenta without MAO-B was unstable in above purifications and used as crude. At each purification step, we checked sensitivity of the enzyme to specific inhibitors by developing a convenient fluorescence assay, in which hydrogen peroxide produced by the enzyme was reacted with p-hydroxyphenylpropionic acid. A fluorescence microplate reader measured a fluorescence of the fluorescent product from p-hydroxyphenylpropionic acid with horseradish peroxidase. In comparison with milacemide, N,N-bis(carbamoylmethyl)-N-pentylamine was the best and exclusive substrate for MAO-B. 2-N-(phenylethylamino)-acetoamide was the good substrate for MAO-A and MAO-B same as milacemide. 4-N-(n-pentylamino)-butyric acid and 4-(N-phenylethylamino)-butyric acid were the moderate substrates for both enzymes, which should release gamma-aminobutyric acid. These drugs will be new leading compounds. |
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Authors:
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Motomi Matsukawa; Toshikazu Hirai; Shoko Karita; Toshifumi Akizawa; Hidemitsu Pan-Hou; Masanori Yoshioka; Giichi Goto; Hasan Parvez; Moussa B H Youdim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neurotoxicology Volume: 25 ISSN: 0161-813X ISO Abbreviation: Neurotoxicology Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2003-12-30 Completed Date: 2004-04-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7905589 Medline TA: Neurotoxicology Country: Netherlands |
Other Details:
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Languages: eng Pagination: 293-302 Citation Subset: IM |
Affiliation:
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Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotogecho, Hirakata, Osaka, 573-0101, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dose-Response Relationship, Drug Drug Evaluation, Preclinical / methods Female Guinea Pigs Humans Mitochondria, Liver / drug effects, enzymology Monoamine Oxidase / metabolism* Monoamine Oxidase Inhibitors / analysis, chemistry, pharmacology* Prodrugs / analysis, chemistry, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Monoamine Oxidase Inhibitors; 0/Prodrugs; EC 1.4.3.4/Monoamine Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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