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Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has garnered attention since its approval for amyotrophic lateral sclerosis in Japan (2015) and the United States (2017). Edaravone is administered intravenously, and as such, is distributed in the form of an aqueous solution. However, aqueous solution...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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the Society for Free Radical Research Japan
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703789/ https://www.ncbi.nlm.nih.gov/pubmed/29203956 http://dx.doi.org/10.3164/jcbn.17-75 |
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author | Tanaka, Masahiko Motomiya, Satsuki Fujisawa, Akio Yamamoto, Yorihiro |
author_facet | Tanaka, Masahiko Motomiya, Satsuki Fujisawa, Akio Yamamoto, Yorihiro |
author_sort | Tanaka, Masahiko |
collection | PubMed |
description | Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has garnered attention since its approval for amyotrophic lateral sclerosis in Japan (2015) and the United States (2017). Edaravone is administered intravenously, and as such, is distributed in the form of an aqueous solution. However, aqueous solutions of edaravone are very unstable because they present as edaravone anions, which become edaravone radicals when the anion donates an electron to free radicals including oxygen. In this study, glutathione (GSH) stabilized an aqueous edaravone solution during storage at 60°C for 4 weeks, and prevented the formation of potentially carcinogenic phenylhydrazine, while cysteine did not. One possible explanation is that GSH undergoes intermolecular hydrogen bonding with edaravone anions, while cysteine does not, as it favors intramolecular hydrogen boding. The combination of GSH and sodium bisulfite (NaHSO(3)) stabilized aqueous edaravone at room temperature for more than 1 year even under aerobic conditions. However, the U.S. Food and Drug Administration cautioned that NaHSO(3) may cause allergic reactions. Therefore, we developed a stable edaravone aqueous solution without using NaHSO(3), namely a combination of GSH with deoxygenation, which resulted in better stabilization of aqueous edaravone than the combination of GSH and NaHSO(3). |
format | Online Article Text |
id | pubmed-5703789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | the Society for Free Radical Research Japan |
record_format | MEDLINE/PubMed |
spelling | pubmed-57037892017-12-04 Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione Tanaka, Masahiko Motomiya, Satsuki Fujisawa, Akio Yamamoto, Yorihiro J Clin Biochem Nutr Original Article Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has garnered attention since its approval for amyotrophic lateral sclerosis in Japan (2015) and the United States (2017). Edaravone is administered intravenously, and as such, is distributed in the form of an aqueous solution. However, aqueous solutions of edaravone are very unstable because they present as edaravone anions, which become edaravone radicals when the anion donates an electron to free radicals including oxygen. In this study, glutathione (GSH) stabilized an aqueous edaravone solution during storage at 60°C for 4 weeks, and prevented the formation of potentially carcinogenic phenylhydrazine, while cysteine did not. One possible explanation is that GSH undergoes intermolecular hydrogen bonding with edaravone anions, while cysteine does not, as it favors intramolecular hydrogen boding. The combination of GSH and sodium bisulfite (NaHSO(3)) stabilized aqueous edaravone at room temperature for more than 1 year even under aerobic conditions. However, the U.S. Food and Drug Administration cautioned that NaHSO(3) may cause allergic reactions. Therefore, we developed a stable edaravone aqueous solution without using NaHSO(3), namely a combination of GSH with deoxygenation, which resulted in better stabilization of aqueous edaravone than the combination of GSH and NaHSO(3). the Society for Free Radical Research Japan 2017-11 2017-10-26 /pmc/articles/PMC5703789/ /pubmed/29203956 http://dx.doi.org/10.3164/jcbn.17-75 Text en Copyright © 2017 JCBN http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Tanaka, Masahiko Motomiya, Satsuki Fujisawa, Akio Yamamoto, Yorihiro Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione |
title | Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione |
title_full | Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione |
title_fullStr | Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione |
title_full_unstemmed | Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione |
title_short | Stabilizers of edaravone aqueous solution and their action mechanisms. 2. Glutathione |
title_sort | stabilizers of edaravone aqueous solution and their action mechanisms. 2. glutathione |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703789/ https://www.ncbi.nlm.nih.gov/pubmed/29203956 http://dx.doi.org/10.3164/jcbn.17-75 |
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