Description
Idebenone(58186-27-9) is an organic compound belonging to the quinone family, being similar to coenzyme Q-10. It is a kind of drug developed by Takeda Pharmaceutical Company for the treatment of Alzheimer’s disease and some other cognitive defects. However, these have been not very much progress associated with this indication. It is now also used for the treatment of Friedreich’s ataxia with a positive effect on cardiac hypertrophy and neurological function. However, this indication is only approved in Canada, not in Europe and US. It is now under investigation on its efficacy for the treatment of Duchenne muscular dystrophy, Leber’s hereditary optic neuropathy, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) as well as primary progressive multiple sclerosis. The efficacy of this drug still demands more evidences.
Chemical Properties
Yellow-Orange Crystalline Solid
Originator
Takeda (Japan)
Application
Idebenone is ubiquinone derivative with protective effects against cerebral ischemia and cognition enhancer. It has been used:
chemotherapy drug
to treat mutant myocilin (mMYOC) cells for drug treatment assay
to validate C2C12 secondary cell screening assay
to treat obese mice, to test whether idebenone and CoQ10 bind directly to peroxisome proliferator-activated receptor (PPAR)LBDs, His-tagged PPARα, δ and γ LBDs
Definition
ChEBI: A member of the class of 1,4-benzoquinones which is substituted by methoxy groups at positions 2 and 3, by a methyl group at positions 5, and by a 10-hydroxydecyl group at positions 6. Initially developed for the treatment of Alzheimer's disease, benefits
ere modest; it was subsequently found to be of benefit for the symptomatic treatment of Friedreich's ataxia.
General Description
Idebenone is a short-chain benzoquinone drug.
Biological Activity
Antioxidant and neuroprotective agent. Protects mitochondrial membranes against lipid peroxidation and blocks glutamate neurotoxicity in vitro and in vivo . Inhibits apoptosis of astrocytes via increased NGF production.
Biochem/physiol Actions
Idebenone is used in the treatment of visual impairment in adolescents and adults with Leber′s hereditary optic neuropathy (LHON). It serves as an antioxidant. It helps to guard the heart muscle against oxidative stress.
Side effects
The most common adverse reactions to Idebenone are mild to moderate diarrhoea (usually without the need to stop treatment), nasopharyngitis, cough and back pain.
The following adverse reactions emerging from clinical trials in LHON patients or reported postmarketing in other indications are tabulated below. Frequency groupings are defined to the following
convention: very common (≥1/10), common (≥1/100 to<1/10), not known (cannot be estimated from
the available data).
Mode of action
The mechanism of action of idebenone involves its antioxidant properties and ability to act as a mitochondrial electron carrier. Idebenone overcomes mitochondrial complex I respiratory chain deficiency in patients with LHON by transferring electrons directly to mitochondrial complex III (by-passing complex I), thereby restoring cellular energy (ATP) production and re-activating inactive-but-viable retinal ganglion cells, which ultimately prevents further vision loss and promotes vision recovery.
PID27071925
References
1) Zs-Nagy (1990) Chemistry, toxicology, pharmacology and pharmacokinetics of idebenone: a review; Gerontol. Geriatr., 11, 177
2) Civenni et al. (1999) Inhibitory effect of the neuroprotetive agent idebenone on arachidonic acid metabolism in astrocytes; Eur. J. Pharmacol., 370 161
3) Takuma et al. (2000) CV-2619 protects cultured astrocytes against reperfusion injury via nerve growth factor production; Eur. J. Pharmacol., 406 333
4) Gerhardt et al. (2011) Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice; PloS One, 6 e28855
