Idebenone exists in two distinct oxidative states: reduced idebenone, which is a ubiquinol derivative, and oxidized idebenone, which is a ubiquinone derivative. This molecule has protective activity against neurotoxicity in both in vitro and in vivo models[1]. The oxidized form of idebenone preferentially inhibits the metabolism of cyclooxygenase over lipoxygenase (IC50 ratio lipoxygenase/cyclooxygenase: 3.22)[1]. The oxidized version of idebenone functions similarly to two common anti-inflammatory drugs, piroxicam and indomethacin[1]. For a duration of 24 to 72 hours, idebenone (1–10 μM) had no influence on the viability of SHSY-5Y cells [2]. Idebenone (at 25 μM or greater doses; for 24-72 h) significantly lowers SHSY-5Y cell viability[2]. Idebenone (30 μM) causes the expression of BAX and caspase-3 activity to be upregulated[2].

Idebenone (oxidised form) is a chemical with preventive activity against cerebrovascular diseases in vivo, including cerebral ischemia and hypertension-induced vascular lesions[1].

Cell Viability Assay[2]
Cell Types: The human dopaminergic neuroblastma cell line, SHSY-5Y cells
Tested Concentrations: 1, 3, 10, 15, 25, 30, and 90 μM
Incubation Duration: 24, 48, and 72 hrs (hours)
Experimental Results: Had no apparent detrimental effects on cell viability as indicated by the absence of trypan blue-positive staining in the cells at concentrations of 1, 3, 10 μM. demonstrated some degree of trypan blue-positive staining at 15 μM. demonstrated extensive trypan blue-positive staining at 25 μM and 30 μM.

---

RT-PCR[2]
Cell Types: SHSY-5Y cells
Tested Concentrations: 10 μM, 30 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: The total RNA of BAX from SHSY-5Y cells exposed to 10 μM was not different from that of the untreated control cells. The BAX expression in SHSY-5Y cells exposed to 30 μM was Dramatically up-regulated when compared with the untreated control cells and cells exposed to 10 μM.

Absorption, Distribution and Excretion
After oral administration, idebenone is rapidly absorbed. On repeat dosing, maximum plasma concentrations of idebenone are reached on average within 1 hour (median 0.67 h range: 0.33-2.00 h). Food increases the bioavailability of idebenone by approximately 5-7-fold and i therefore should always be administered with food.
The main route of elimination is metabolism, with the majority of dose excreted via the kidneys as metabolites. After a single or repeated oral dose of 750 mg of idebenone, QS4+QS4-C were the most prominent idebenone-derived metabolites in urine, representing on average between 49.3% and 68.3% of the total administered dose. QS6+QS6 represented 6.45% to 9.46%, whereas QS10+QS10-C and IDE+IDE-C were close to 1% or below.
Experimental data have shown that idebenone passes the blood-brain barrier and is distributed at significant concentrations in cerebral tissue. Following oral administration pharmacologically relevant concentrations of idebenone are detectable in the aqueous humor of the eye.

---

Metabolism / Metabolites
Metabolism occurs by means of oxidative shortening of the side chain and by reduction of the quinone ring and conjugation to glucuronides and sulphates. Idebenone shows a high first pass metabolism resulting in conjugates of idebenone (glucuronides and sulphates (IDE-C)) and the Phase I metabolites QS10, QS6, and QS4 as well as their corresponding Phase II metabolites (glucuronides and sulphates (QS10+QS10-C, QS6+QS6-C, QS4+QS4-C)). The main metabolites in plasma are IDE-C and QS4+QS4-C.

[1]. Inhibitory effect of the neuroprotective agent idebenone on arachidonic acid metabolism in astrocytes.Eur J Pharmacol. 1999 Apr 9;370(2):161-7.

[2]. Idebenone induces apoptotic cell death in the human dopaminergic neuroblastoma SHSY-5Y cells. Neurotox Res. 2011 Nov;20(4):321-8.

Idebenone is 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 were modest; it was subsequently found to be of benefit for the symptomatic treatment of Friedreich's ataxia. It has a role as an antioxidant and a ferroptosis inhibitor. It is a primary alcohol and a member of 1,4-benzoquinones.
Idebenone is a synthetic analogue of ubiquinone (also known as Coenzyme Q10), a vital cell antioxidant and essential component of the Electron Transport Chain (ETC). It has been proposed that by interacting with the ETC, idebenone increases ATP production required for mitochondrial function, reduces free radicals, inhibits lipid peroxidation, and consequently protects the lipid membrane and mitochondria from oxidative damage. More specifically, idebenone is thought to transfer electrons directly to complex III of the mitochondrial ETC, thereby circumventing complex I and restoring cellular energy (ATP) generation. Due to its ability to reduce oxidative damage and improve ATP production, idebenone was originally investigated for its potential use in Alzheimer's Disease and other cognitivie disorders. Lack of improvement in cognitive function halted its production for these conditions, however it continues to be investigated for use in other conditions associated with mitochondrial damage. Idebenone is currently only indicated for use by the European Medicines Agency (EMA) for the treatment of visual impairment in adolescent and adult patients with Leber’s Hereditary Optic Neuropathy (LHON). LHON is a mitochondrially inherited degeneration of retinal ganglion cells, resulting in acute central vision loss. Due to its biochemical mode of action, it's thought that idebenone may re-activate viable-but-inactive retinal ganglion cells (RGCs) in LHON patients. It is not currently approved for use by either the Food and Drug Administration (USA) or Health Canada.

---

Drug Indication
Idebenone is indicated for use by the European Medicines Agency (EMA) for the treatment of visual impairment in adolescent and adult patients with Leber’s Hereditary Optic Neuropathy (LHON). It is not currently approved for use by either the Food and Drug Administration (USA) or Health Canada.
Raxone is indicated for the treatment of visual impairment in adolescent and adult patients with Leber's Hereditary Optic Neuropathy (LHON).
Treatment of Friedreich’s Ataxia

---

Mechanism of Action
Idebenone is a synthetic analogue of ubiquinone (also known as Coenzyme Q10), a vital cell antioxidant and essential component of the Electron Transport Chain (ETC). It has been proposed that by interacting with the ETC, idebenone increases ATP production required for mitochondrial function, reduces free radicals, inhibits lipid peroxidation, and consequently protects the lipid membrane and mitochondria from oxidative damage. More specifically, idebenone is thought to transfer electrons directly to complex III of the mitochondrial ETC, thereby circumventing complex I and restoring cellular energy (ATP) generation.

C19H30O5

338.44

338.209

58186-27-9

3686

Yellow to orange solid powder

1.1±0.1 g/cm3

497.3±45.0 °C at 760 mmHg

52-550C

170.1±22.2 °C

0.0±2.9 mmHg at 25°C

1.502

3.49

1

5

12

24

502

0

JGPMMRGNQUBGND-UHFFFAOYSA-N

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

2-(10-Hydroxydecyl)-5,6-dimethoxy-3-methyl-p-benzoquinone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)