Idebenone

2022-11-20:

Idebenone #

Synthetic CoQ10 analogue by Takeda.

• Photobiomodulation + Methylene Blue + Idebenone = Peak Mitochondrial Optimization
• https://www.reddit.com/r/NooTopics/comments/z404cd/the_synergy_between_idebenone_and_carnosic_acid/

• The idebenone metabolite QS10 restores electron transfer in complex I and coenzyme Q defects
  • Its metabolites are relevant for its ETC activity:
    • QS10 restores respiration in C1/CoQ deficient cells without inducing mitochondrial permeability transition - unlike idebenone.
• Dose-effect relationship of idebenone in an experimental cerebral deficit model. Pilot study in healthy young volunteers with piracetam as reference drug
  • Due to low lipophilicity, idebenone can inhibit Complex I, generating Superoxide. NQO1 counters this generation, but its production is limited by NRF2. That’s where Carnosic Acid comes in, as it activates NRF2.
• Idebenone-Activating Autophagic Degradation of α-Synuclein via Inhibition of AKT-mTOR Pathway in a SH-SY5Y-A53T Model of Parkinson’s Disease: A Network Pharmacological Approach
• [Idebenone improves learning and memory impairment induced by cholinergic or serotonergic dysfunction in rats]
• Mitochondrial respiration without ubiquinone biosynthesis
  • We demonstrated that efficient rescue of the respiratory deficiency in UQ-deficient cells by UQ analogues is side chain length dependent, and that classical UQ analogues with alkyl side chains such as idebenone and decylUQ are inefficient in comparison with analogues with isoprenoid side chains
  • Has been suggested to penetrate better into tissues/mitochondria than UQ.
  • Poor electron acceptor for complex I; it has poor efficacy at replacing UQ10 in deficiency.
• Very potent ‘antioxidant’: Idebenone: When an antioxidant is not an antioxidant
  • Instead of being a direct antioxidant, idebenone increases the ability of cells to counteract oxidative stress by upregulating their physiological defence mechanisms and decreasing the production of oxidative radicals. However, there is significant doubt that protection against ROS-induced damage is the only molecular activity of idebenone that confers cytoprotection.
• Potentiation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor function by a nootropic drug, idebenone
• Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy
  • Quinone analogues can have a detrimental effect on certain mitochondrial parameters when tested in vitro.
• The effects of idebenone on mitochondrial bioenergetics
• Novel idebenone analogs block Shc’s access to insulin receptor to improve insulin sensitivity

Dose #

• Only like 3-16% oral bioavailability