- 関
- subacute myelo-optic neuropathy、subacute myelo-optico-neuropathy
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/19 15:43:49」(JST)
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English Journal
- The solution structure of the copper clioquinol complex.
- Pushie MJ1, Nienaber KH1, Summers KL2, Cotelesage JJ3, Ponomarenko O1, Nichol HK4, Pickering IJ5, George GN6.Author information 1Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada.2Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Department of Chemistry, University of Saskatchewan, SK S7N 5C9, Canada.3Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Canadian Light Source Inc., Saskatoon, SK S7N 2V3, Canada.4Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.5Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada.6Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada. Electronic address: g.george@usask.ca.AbstractClioquinol (5-chloro-7-iodo-8-hydroxyquinoline) recently has shown promising results in the treatment of Alzheimer's disease and in cancer therapy, both of which also are thought to be due to clioquinol's ability as a lipophilic copper chelator. Previously, clioquinol was used as an anti-fungal and anti-protozoal drug that was responsible for an epidemic of subacute myelo-optic neuropathy (SMON) in Japan during the 1960s, probably a myeloneuropathy arising from a clioquinol-induced copper deficiency. Previous X-ray absorption spectroscopy of solutions of copper chelates of clioquinol suggested unusual coordination chemistry. Here we use a combination of electron paramagnetic, UV-visible and X-ray absorption spectroscopies to provide clarification of the chelation chemistry between clioquinol and copper. We find that the solution structures for the copper complexes formed with stoichiometric and excess clioquinol are conventional 8-hydroxyquinolate chelates. Thus, the promise of clioquinol in new treatments for Alzheimer's disease and in cancer therapy is not likely to be due to any novel chelation chemistry, but rather due to other factors including the high lipophilicity of the free ligand and chelate complexes.
- Journal of inorganic biochemistry.J Inorg Biochem.2014 Jan 16;133C:50-56. doi: 10.1016/j.jinorgbio.2014.01.003. [Epub ahead of print]
- Clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) recently has shown promising results in the treatment of Alzheimer's disease and in cancer therapy, both of which also are thought to be due to clioquinol's ability as a lipophilic copper chelator. Previously, clioquinol was used as an anti-fungal and
- PMID 24503514
- Clioquinol induces DNA double-strand breaks, activation of ATM, and subsequent activation of p53 signaling.
- Katsuyama M1, Iwata K, Ibi M, Matsuno K, Matsumoto M, Yabe-Nishimura C.Author information 1Radioisotope Center, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. mkatsuya@koto.kpu-m.ac.jpAbstractClioquinol, a Cu²⁺/Zn²⁺/Fe²⁺ chelator/ionophor, was used extensively in the mid 1900s as an amebicide for treating indigestion and diarrhea. It was eventually withdrawn from the market because of a link to subacute myelo-optic neuropathy (SMON) in Japan. The pathogenesis of SMON, however, is not fully understood. To clarify the molecular mechanisms of clioquinol-induced neurotoxicity, a global analysis using DNA chips was carried out on human neuroblastoma cells. The global analysis and quantitative PCR demonstrated that mRNA levels of p21(Cip1), an inhibitor of cyclins D and E, and of GADD45α, a growth arrest and DNA damage-inducible protein, were significantly increased by clioquinol treatment in SH-SY5Y and IMR-32 neuroblastoma cells. Activation of p53 by clioquinol was suggested, since clioquinol induced phosphorylation of p53 at Ser15 to enhance its stabilization. The phosphorylation of p53 was inhibited by KU-55933, an inhibitor of ataxia-telangiectasia mutated kinase (ATM), but not by NU7026, an inhibitor of DNA-dependent protein kinase (DNA-PK). Clioquinol in fact induced phosphorylation of ATM and histone H2AX, a marker of DNA double-strand breaks (DSBs). These results suggest that clioquinol-induced neurotoxicity is mediated by DSBs and subsequent activation of ATM/p53 signaling.
- Toxicology.Toxicology.2012 Sep 4;299(1):55-9. doi: 10.1016/j.tox.2012.05.013. Epub 2012 May 22.
- Clioquinol, a Cu²⁺/Zn²⁺/Fe²⁺ chelator/ionophor, was used extensively in the mid 1900s as an amebicide for treating indigestion and diarrhea. It was eventually withdrawn from the market because of a link to subacute myelo-optic neuropathy (SMON) in Japan. The pathogenesis of SMON, however, i
- PMID 22627294
- Clioquinol: review of its mechanisms of action and clinical uses in neurodegenerative disorders.
- Bareggi SR1, Cornelli U.Author information 1Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, University of Milan, Italy. silvio.bareggi@unimi.itAbstractClioquinol was produced as a topical antiseptic and marketed as an oral intestinal amebicide in 1934, being used to treat a wide range of intestinal diseases. In the early 1970s, it was withdrawn from the market as an oral agent because of its association with subacute myelo-optic neuropathy (SMON), a syndrome that involves sensory and motor disturbances in the lower limbs and visual changes. The first methods for determining plasma and tissue clioquinol (5-chloro-7-iodo-8-quinolinol) levels were set up in the 1970s and involved HPLC separation with UV detection, these were followed by a more sensitive GC method with electron capture detection and a gaschromatographic-massspectrometric (GC-MS) method. Finally, an HPLC method using electrochemical detection has proved to be as highly sensitive and specific as the GC-MS. In rats, mice, rabbits, and hamsters, clioquinol is rapidily absorbed and undergoes first-pass metabolization to glucuronate and sulfate conjugates; the concentrations of the metabolites are higher than those of free clioquinol. Bioavailabilty versus intraperitoneal dosing is about 12%. Dogs and monkeys form fewer conjugates. In man, single-dose concentrations are dose related, and the drug's half-life is 11-14 h. There is no accumulation, and the drug is much less metabolized to conjugates. Clioquinol acts as a zinc and copper chelator. Metal chelation is a potential therapeutic strategy for Alzheimer's disease (AD) because zinc and copper are involved in the deposition and stabilization of amyloid plaques, and chelating agents can dissolve amyloid deposits in vitro and in vivo. In general, the ability of clioquinol to chelate and redistribute metals plays an important role in diseases characterised by Zn, Cu, Fe dyshomeostasis, such as AD and Parkinson's disease, as it reduces oxidation and the amyloid burden. Zinc chelators may also act as anticancer agents. Animal toxicity studies have revealed species-specific differences in neurotoxic responses that are related to the serum levels of clioquinol and metabolites. This is also true in humans, who form fewer conjugates. The results of studies of Alzheimer patients are conflicting and need further confirmation. The potential therapeutic role of the two main effects of MPACs (the regulation of the distribution of metals and antioxidants) has not yet been fully explored.
- CNS neuroscience & therapeutics.CNS Neurosci Ther.2012 Jan;18(1):41-6. doi: 10.1111/j.1755-5949.2010.00231.x. Epub 2010 Dec 27.
- Clioquinol was produced as a topical antiseptic and marketed as an oral intestinal amebicide in 1934, being used to treat a wide range of intestinal diseases. In the early 1970s, it was withdrawn from the market as an oral agent because of its association with subacute myelo-optic neuropathy (SMON),
- PMID 21199452
Japanese Journal
- カルマ・チャクメーの極楽願文『清浄大楽国土の誓願』の和訳と研究 : 往生の第二因、七支供養より随喜・勧請・祈願の段
- 中御門 敬教
- 佛教大学総合研究所紀要 19, 19-34, 2012-03-25
- NAID 110008920901
- カルマ・チャクメーの極楽願文『清浄大楽国土の誓願』の和訳と研究 : 往生の第二因、七支供養より懺悔の段
- 藤仲 孝司
- 佛教大学総合研究所紀要 19, 1-18, 2012-03-25
- NAID 110008920900
Related Links
- 薬害防止のために薬剤師のやるべきことは何か 考えてみよう ... 薬害スモン（SMON）とは 薬害スモンとは、整腸剤キノホルムを服用することによって、神経障害患者が多数発生した事件のことをいう。
- 経過、臨床症状、病理学的所見からつけた英語subacute myelo-optico-neuropathy（亜急性脊髄・視神経・末梢神経障害）の頭文字SMON からつけた疾患です。
Related Pictures
★リンクテーブル★
| 国試過去問 | 「087B071」 |
| リンク元 | 「多発性神経障害」「スモン」「キノホルム」「キノホルム中毒」「亜急性脊髄視神経ニューロパシー」 |
| 関連記事 | 「SM」「SMO」 |
「087B071」
- 疾患と原因の組み合わせで間違っている物
「多発性神経障害」
- 両側対称性に複数の末梢神経障害が出現する。左右差はない。
- 四肢末梢優位に冒されるのが特徴的である。典型的には手袋靴下型の分布をとり、初期には靴下型から始める。
- ギラン･バレー症候群
- シャルコー・マリー・トゥース病
- 家族性アミロイドニューロパチー
- 糖尿病
- ビタミンB1欠乏症
- 急性間欠性ポルフィリン症
- 癌性ニューロパチー
- SMON
「スモン」
概念
参考
- 1. スモン - 難病情報センター
「キノホルム」
- 英
- chinoform
- ラ
- chinoformum
- 同
- iodochlorhydroxyquin、クリオキノール clioquinol,chloroiodoquie, clioquinolum
副作用
「キノホルム中毒」
- 英
- chinoform poisoning
- 同
- ヨードクロルヒドロキシキン中毒 iodochlorhydroxyquin poisoning、クリオキノール中毒 clioquinol poisoning
- 関
- SMON スモン