Idebenone
|
Systematic (IUPAC) name |
2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl-
cyclohexa-2,5-diene-1,4-dione |
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 Y |
ATC code |
N06BX13 |
PubChem |
CID 3686 |
ChemSpider |
3558 Y |
UNII |
HB6PN45W4J Y |
KEGG |
D01750 Y |
ChEMBL |
CHEMBL252556 Y |
Chemical data |
Formula |
C19H30O5 |
Mol. mass |
338.439 g/mol |
SMILES
- O=C1/C(=C(\C(=O)C(\OC)=C1\OC)C)CCCCCCCCCCO
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InChI
-
InChI=1S/C19H30O5/c1-14-15(12-10-8-6-4-5-7-9-11-13-20)17(22)19(24-3)18(23-2)16(14)21/h20H,4-13H2,1-3H3 Y
Key:JGPMMRGNQUBGND-UHFFFAOYSA-N Y
|
Y (what is this?) (verify)
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Idebenone (pronounced eye-deb-eh-known, trade names Catena and Sovrima) is a drug that was 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).
Contents
- 1 Uses
- 1.1 Indications that are approved in some territories
- 1.1.1 Nootropic effects and Alzheimer's disease
- 1.1.2 Friedreich's ataxia
- 1.2 Indications being explored
- 1.2.1 Duchenne muscular dystrophy
- 1.2.2 Other neuromuscular diseases
- 1.2.3 Leber's hereditary optic neuropathy
- 1.3 Life style
- 2 Adverse effects, contraindications and interactions
- 3 Pharmacology
- 4 References
Uses[edit]
Indications that are approved in some territories[edit]
Nootropic effects and Alzheimer's disease[edit]
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]
Friedreich's ataxia[edit]
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]
The drug was approved for FA in Canada in 2008 under conditions including proof of efficacy in further clinical trials.[11] However on February 27, 2013, Health Canada announced that idebenone would be voluntarily recalled as of April 30, 2013 by its Canadian manufacturer, Santhera Pharmaceuticals, due to the failure of Cantera to show efficacy in the further clinical trials that were conducted.[12] As of 2010 the drug was not approved for FA in Europe[13] nor in the US, where there is no approved treatment.[14]
Indications being explored[edit]
Duchenne muscular dystrophy[edit]
After experiments in mice[15] and preliminary studies in humans, idebenone has entered Phase II clinical trials in 2005[3] and Phase III trials in 2009.[16]
Other neuromuscular diseases[edit]
Phase I and II clinical trials for the treatment of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)[17] and primary progressive multiple sclerosis[18] are recruiting patients as of May 2010[update], a study investigating Leber's hereditary optic neuropathy is under way.[19]
Leber's hereditary optic neuropathy[edit]
Leber's hereditary optic neuropathy(LHON)is a mitochondrially inherited (mother to all offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. Santhera completed a Phase III clinical trial in this indication in Europe with positive results,[20] and submitted an application to market the drug to European regulators in July 2011.[21]
Life style[edit]
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.[22]
Adverse effects, contraindications and interactions[edit]
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This section is empty. You can help by adding to it. (May 2012) |
Pharmacology[edit]
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This section requires expansion. (May 2010) |
Idebenone inhibits lipoperoxide formation.[23]
References[edit]
- ^ a b CHMP Assessment Report for Sovrima. European Medicines Agency. 20 November 2008. p. 6.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Heath Canada Fact Sheet - Catena
- ^ Voluntary Withdrawal of Catena from the Canadian Market
- ^ Margaret Wahl for Quest Magazine, MAY 28, 2010. FA Research: Idebenone Strikes Out Again
- ^ NINDS Fact Sheet
- ^ 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.
- ^ 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)
- ^ Klopstock T, et al (2011) A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain.134(Pt 9):2677-86.
- ^ Staff, European Biotechnology News, July 26, 2011. Santhera publishes pivotal trial results of idebenone and goes for EU approval
- ^ 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]". Nippon Yakurigaku Zasshi (in Japanese) 91 (5): 295–9. doi:10.1254/fpj.91.295. PMID 3410376.
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