Idebenone
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| Systematic (IUPAC) name | |
| 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl- cyclohexa-2,5-diene-1,4-dione |
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| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Pregnancy cat. | ? |
| Legal status | Investigational |
| Pharmacokinetic data | |
| Half-life | 18 hours |
| Excretion | urine and feces |
| Identifiers | |
| CAS number | 58186-27-9  |
| ATC code | N06BX13 |
| PubChem | CID 3686 |
| ChemSpider | 3558 |
| UNII | HB6PN45W4J |
| KEGG | D01750 |
| ChEMBL | CHEMBL252556 |
| Chemical data | |
| Formula | C19H30O5 |
| Mol. mass | 338.439 g/mol |
| SMILES | eMolecules & PubChem |
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Idebenone (pronounced eye-deb-eh-known, trade names Catena and Sovrima) is an experimental drug, initially developed by Takeda Pharmaceutical Company for the treatment of Alzheimer's disease and other cognitive defects.[1] This has been met with limited success. The Swiss company Santhera Pharmaceuticals has started to investigate it for the treatment of neuromuscular diseases. As of May 2010[update], early clinical trials for the treatment of Friedreich's ataxia[2] and Duchenne muscular dystrophy[3] have been completed. Chemically, idebenone is an organic compound of the quinone family. It is also promoted commercially as a synthetic analog of coenzyme Q10 (CoQ10).
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[edit] Uses
[edit] Pharmaceutical indications
[edit] Nootropic effects and Alzheimer's disease
Idebenone improved learning and memory in experiments with mice.[4] In humans, evaluation of Surrogate endpoints like electroretinography, auditory evoked potentials and visual analogue scales also suggested positive nootropic effects,[5] but larger studies with hard endpoints are missing.
Research on idebenone as a potential therapy of Alzheimer's disease have been inconsistent, but there may be a trend for a slight benefit.[6][7] In May 1998, the approval for this indication was cancelled in Japan due to the lack of proven effects. In some European countries, the drug is available for the treatment of individual patients in special cases.[1]
[edit] Friedreich's ataxia
Preliminary testing has been done in humans and found idebenone to be a safe treatment for Friedreich's ataxia, exhibiting a positive effect on cardiac hypertrophy and neurological function.[8] The latter was only significantly improved in young patients.[9] In a different experiment, a one-year test on eight patients, idebenone reduced the rate of deterioration of cardiac function, but without halting the progression of ataxia.[10]
[edit] Duchenne muscular dystrophy
After experiments in mice[11] and preliminary studies in humans, idebenone has entered Phase II clinical trials in 2005[3] and Phase III trials in 2009.[12]
[edit] Other neuromuscular diseases
Phase I and II clinical trials for the treatment of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)[13] and primary progressive multiple sclerosis[14] are recruiting patients as of May 2010[update], a study investigating Leber's hereditary optic neuropathy is under way.[15]
[edit] Life style
Idebenone is claimed to have properties similar to CoQ10 in its antioxidant properties, and has therefore been used in anti-aging on the basis of free-radical theory. Clinical evidence for this use is missing. It has been used in topical applications to treat wrinkles.[16]
[edit] Pharmacology
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Idebenone inhibits lipoperoxide formation.[17]
[edit] History
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This section requires expansion. |
On July 23, 2008, Health Canada issued a Notice of Compliance under the Notice of Compliance with Conditions (NOC/c) Policy to Santhera Pharmaceuticals (Switzerland) for the drug product Catena. The product was authorized under the NOC/c Policy on the basis of the promising nature of the clinical evidence, and the need for a confirmatory study to verify its clinical benefit. Patients should be advised of the fact that the market authorization was issued with conditions.
[edit] References
- ^ a b CHMP Assessment Report for Sovrima. European Medicines Agency. 20 November 2008. p. 6. http://www.ema.europa.eu/humandocs/PDFs/EPAR/Sovrima/H-908-en6.pdf.
- ^ ClinicalTrials.gov NCT00229632 Idebenone to Treat Friedreich's Ataxia
- ^ a b ClinicalTrials.gov NCT00654784 Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy (DELPHI)
- ^ Liu, XJ; Wu, WT (1999). "Effects of ligustrazine, tanshinone II A, ubiquinone, and idebenone on mouse water maze performance.". Zhongguo yao li xue bao = Acta pharmacologica Sinica 20 (11): 987–90. PMID 11270979.
- ^ Schaffler, K; Hadler, D; Stark, M (1998). "Dose-effect relationship of idebenone in an experimental cerebral deficit model. Pilot study in healthy young volunteers with piracetam as reference drug.". Arzneimittel-Forschung 48 (7): 720–6. PMID 9706371.
- ^ Gutzmann, H; Kühl, KP; Hadler, D; Rapp, MA (2002). "Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: results of a randomized, double-blind, parallel-group multicenter study.". Pharmacopsychiatry 35 (1): 12–8. doi:10.1055/s-2002-19833. PMID 11819153.
- ^ Parnetti, L; Senin, U; Mecocci, P (1997). "Cognitive enhancement therapy for Alzheimer's disease. The way forward.". Drugs 53 (5): 752–68. doi:10.2165/00003495-199753050-00003. PMID 9129864.
- ^ Di Prospero NA, Baker A, Jeffries N, Fischbeck KH (October 2007). "Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial". Lancet Neurol 6 (10): 878–86. doi:10.1016/S1474-4422(07)70220-X. PMID 17826341. http://linkinghub.elsevier.com/retrieve/pii/S1474-4422(07)70220-X.
- ^ Tonon C, Lodi R (September 2008). "Idebenone in Friedreich's ataxia". Expert Opin Pharmacother 9 (13): 2327–37. doi:10.1517/14656566.9.13.2327. PMID 18710357. http://www.expertopin.com/doi/abs/10.1517/14656566.9.13.2327.
- ^ Buyse G, Mertens L, Di Salvo G, et al. (May 2003). "Idebenone treatment in Friedreich's ataxia: neurological, cardiac, and biochemical monitoring". Neurology 60 (10): 1679–81. PMID 12771265. http://www.neurology.org/cgi/pmidlookup?view=long&pmid=12771265.
- ^ Buyse, GM; Van Der Mieren, G; Erb, M; D'hooge, J; Herijgers, P; Verbeken, E; Jara, A; Van Den Bergh, A et al (2009). "Long-term blinded placebo-controlled study of SNT-MC17/idebenone in the dystrophin deficient mdx mouse: cardiac protection and improved exercise performance.". European Heart Journal 30 (1): 116–24. doi:10.1093/eurheartj/ehn406. PMC 2639086. PMID 18784063. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2639086.
- ^ ClinicalTrials.gov NCT01027884 Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD) (DELOS)
- ^ ClinicalTrials.gov NCT00887562 Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes (MELAS)
- ^ ClinicalTrials.gov NCT00950248 Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis (IPPoMS)
- ^ ClinicalTrials.gov NCT00747487 Study to Assess Efficacy, Safety and Tolerability of Idebenone in the Treatment of Leber's Hereditary Optic Neuropathy (RHODOS)
- ^ McDaniel D, Neudecker B, Dinardo J, Lewis J, Maibach H (September 2005). "Clinical efficacy assessment in photodamaged skin of 0.5% and 1.0% idebenone". J Cosmet Dermatol 4 (3): 167–73. doi:10.1111/j.1473-2165.2005.00305.x. PMID 17129261.
- ^ Suno M, Nagaoka A (May 1988). "[Effect of idebenone and various nootropic drugs on lipid peroxidation in rat brain homogenate in the presence of succinate]" (in Japanese). Nippon Yakurigaku Zasshi 91 (5): 295–9. doi:10.1254/fpj.91.295. PMID 3410376.
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