Idebenone (CV-2619) is a synthetic derivative of CoQ10 that appears to retain the antioxidative and bioenergetic effects of its parent compound. It appears to be useful in certain disease states.

This page features 27 unique references to scientific papers.

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1Sources and Structure

1.1. Sources

Idebenone (full structural name of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone and codename of-2619[1]) is a synthetic derivative of ubiquinone (reduced CoQ10).


2.1. Serum

A preliminary test using 150mg Idebenone in two healthy males noted that, after one hour, serum concentrations reached 422.8ng/mL.[2]

2.2. Metabolism

Idebenone can be reduced, and the reduced form subsequently oxidized via cytochrome B of the electron transport chain.[3] The reduced form appears to be the one that mediates anti-lipid peroxidative effects.[1]


3.1. Mechanisms

Idebenone (particularly its reduced form) is highly antioxidative, with IC50 values against oxidative damage in the range of 0.5-10µM.[1]

3.2. Glutaminergic Neurotransmission

In vitro, Idebenone can reduce glutamate-induced toxicity in the range of 0.1-3µM secondary to its antioxidative properties,[4] and at a potency exceeding Vitamin E (requiring 10-100µM) and Vinpocetine (10-100µM).[4] It also appears effective against excitotoxicity associated with ATP depletion (independent of NMDA receptors, but still from glutamate[5]) secondary to its antioxidative effects.[5][6]

Unlike many other compounds, Idebenone appears to be protective against excitotoxicity mediated via the AMPA and kainate receptors but not NMDA[7] although some general neuroprotection from the antioxidative effects may persist on NMDA (as noted elsewhere).[8]

Ischemia (damaging via glutamate) appears to be protected against with idebenone (100mg/kg intraperitoneal injections)[9] and secondary to that a preservation of memory (losses seen with ischemic control).[10]

In periods of excitotoxicity, idebenone appears to exert a protective effect. This is mostly due to the antioxidative effects preventing ATP depletion

50μM idebenone can suppress 4-AP induced glutamate release without affecting basal glutamate release and as this is inhibited by bafilomycin A1 it is thought to be due to reducing exocytosis of glutamate; this was dependent on calcium ions, and mostly CaV2.2 and CaV2.1 channels.[11]

Glutamate release appears to be suppressed with idebenone supplementation, and this suppression is due to less synaptic release of glutamate containing vesicles rather than anything at the level of the synapse

Although idebenone has once failed to alter synaptic sensitivity to glutamate[11] it has elsewhere at 10-100μM been found to enhance signalling via AMPA receptors (those comprising α1 and α2 subunits).[12]

Although it is possible that Idebenone can enhance glutaminergic signalling, there is mixed evidence right now and no in vivo studies to confirm

3.3. Memory and Learning

Impairments (via age or injury) in passive avoidance retention, working memory, and delayed alternation can be reduced or reversed by pretraining administration of 3-30mg/kg idebenone[13][14][15][10] For acute usage, 30mg/kg appears to be optimal when injected (intraperitoneal)[15] whereas 3mg/kg injections are sufficient for chronic studies.[16]

3.4. Alzheimer's

Idebenone has been found to be neuroprotective against β-amyloid peptides[17] which is thought to be related to the antioxidative properties of idebenone (as antioxidants, per se, are neuroprotective).[18] These protective effects have been confirmed in vivo as assessed by a reduction in memory loss.[19]

4Interactions with Organ Systems

4.1. Eyes

Leber’s hereditary optic neuropathy (LHON) has been noted to have remission associated with idebenone supplementation[20] and/or accelerate the rate of recovery,[21] with other case studies, open-label trials, or retrospective assessments noting benefit with supplementation.[22][23][24][25][26] It has since been investigated in a 24 week trial where 900mg of idebenone daily was able to improve visual acuity only in those with discordant visual acuities at baseline.[27]

May have benefit for visual acuity in Leber’s hereditary optic neuropathy at a dosage of around 900mg daily (lower doses may be effective, but to a lesser degree)

Scientific Support & Reference Citations


  1. Suno M, Nagaoka A Inhibition of lipid peroxidation by a novel compound (CV-2619) in brain mitochondria and mode of action of the inhibition. Biochem Biophys Res Commun. (1984)
  2. Nohara Y, et al. Determination of idebenone in plasma by HPLC with post-column fluorescence derivatization using 2-cyanoacetamide. Chem Pharm Bull (Tokyo). (2012)
  3. Sugiyama Y, et al. Effects of idebenone (CV-2619) and its metabolites on respiratory activity and lipid peroxidation in brain mitochondria from rats and dogs. J Pharmacobiodyn. (1985)
  4. Miyamoto M, et al. Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line. J Pharmacol Exp Ther. (1989)
  5. Pereira CM, Oliveira CR Glutamate toxicity on a PC12 cell line involves glutathione (GSH) depletion and oxidative stress. Free Radic Biol Med. (1997)
  6. Pereira C, Santos MS, Oliveira C Metabolic inhibition increases glutamate susceptibility on a PC12 cell line. J Neurosci Res. (1998)
  7. Miyamoto M, Coyle JT Idebenone attenuates neuronal degeneration induced by intrastriatal injection of excitotoxins. Exp Neurol. (1990)
  8. Bruno V, et al. Protective action of idebenone against excitotoxic degeneration in cultured cortical neurons. Neurosci Lett. (1994)
  9. Nagaoka A, et al. Effects of idebenone on neurological deficits, local cerebral blood flow, and energy metabolism in rats with experimental cerebral ischemia. Arch Gerontol Geriatr. (1989)
  10. Yamazaki N, et al. Effects of idebenone on memory impairment induced in ischemic and embolization models of cerebrovascular disturbance in rats. Arch Gerontol Geriatr. (1989)
  11. Chang Y, Lin YW, Wang SJ Idebenone inhibition of glutamate release from rat cerebral cortex nerve endings by suppression of voltage-dependent calcium influx and protein kinase A. Naunyn Schmiedebergs Arch Pharmacol. (2011)
  12. Nakamura S, Kaneko S, Satoh M Potentiation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor function by a nootropic drug, idebenone. Biol Pharm Bull. (1994)
  13. Karasawa Y, et al. Effect of minaprine and other reference drugs on passive avoidance impairment induced by cerebral ischemia in Mongolian gerbils. Jpn J Pharmacol. (1990)
  14. Kiyota Y, et al. Effect of idebenone (CV-2619) on memory impairment observed in passive avoidance task in rats with cerebral embolization. Jpn J Pharmacol. (1985)
  15. Beneficial effects of idebenone on memory impairment in rats.
  16. Pelleymounter MA, Cullen MJ Effects of idebenone on information processing in aged Long-Evans rats. Pharmacol Biochem Behav. (1993)
  17. Hirai K, et al. Idebenone protects hippocampal neurons against amyloid beta-peptide-induced neurotoxicity in rat primary cultures. Naunyn Schmiedebergs Arch Pharmacol. (1998)
  18. Pereira C, Santos MS, Oliveira C Involvement of oxidative stress on the impairment of energy metabolism induced by A beta peptides on PC12 cells: protection by antioxidants. Neurobiol Dis. (1999)
  19. Yamada K, et al. Protective effects of idebenone and alpha-tocopherol on beta-amyloid-(1-42)-induced learning and memory deficits in rats: implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo. Eur J Neurosci. (1999)
  20. Mashima Y, Hiida Y, Oguchi Y Remission of Leber's hereditary optic neuropathy with idebenone. Lancet. (1992)
  21. Mashima Y, et al. Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy. J Neuroophthalmol. (2000)
  22. Cortelli P, et al. Clinical and brain bioenergetics improvement with idebenone in a patient with Leber's hereditary optic neuropathy: a clinical and 31P-MRS study. J Neurol Sci. (1997)
  23. Carelli V, et al. Leber's Hereditary Optic Neuropathy (LHON) with 14484/ND6 mutation in a North African patient. J Neurol Sci. (1998)
  24. Carelli V, et al. Leber's hereditary optic neuropathy (LHON/11778) with myoclonus: report of two cases. J Neurol Neurosurg Psychiatry. (2001)
  25. Barnils N, et al. Response to idebenone and multivitamin therapy in Leber's hereditary optic neuropathy. Arch Soc Esp Oftalmol. (2007)
  26. Carelli V, et al. Idebenone treatment in Leber's hereditary optic neuropathy. Brain. (2011)
  27. Klopstock T, et al. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain. (2011)