A preliminary test using 150mg Idebenone in two healthy males noted that, after one hour, serum concentrations reached 422.8ng/mL.
Idebenone can be reduced, and the reduced form subsequently oxidized via cytochrome B of the electron transport chain. The reduced form appears to be the one that mediates anti-lipid peroxidative effects.
Idebenone (particularly its reduced form) is highly antioxidative, with IC50 values against oxidative damage in the range of 0.5-10µM.
In vitro, Idebenone can reduce glutamate-induced toxicity in the range of 0.1-3µM secondary to its antioxidative properties, and at a potency exceeding Vitamin E (requiring 10-100µM) and Vinpocetine (10-100µM). It also appears effective against excitotoxicity associated with ATP depletion (independent of NMDA receptors, but still from glutamate) secondary to its antioxidative effects.
Unlike many other compounds, Idebenone appears to be protective against excitotoxicity mediated via the AMPA and kainate receptors but not NMDA although some general neuroprotection from the antioxidative effects may persist on NMDA (as noted elsewhere).
Ischemia (damaging via glutamate) appears to be protected against with idebenone (100mg/kg intraperitoneal injections) and secondary to that a preservation of memory (losses seen with ischemic control).
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.
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 it has elsewhere at 10-100μM been found to enhance signalling via AMPA receptors (those comprising α1 and α2 subunits).
Although it is possible that Idebenone can enhance glutaminergic signalling, there is mixed evidence right now and no in vivo studies to confirm
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 For acute usage, 30mg/kg appears to be optimal when injected (intraperitoneal) whereas 3mg/kg injections are sufficient for chronic studies.
Idebenone has been found to be neuroprotective against β-amyloid peptides which is thought to be related to the antioxidative properties of idebenone (as antioxidants, per se, are neuroprotective). These protective effects have been confirmed in vivo as assessed by a reduction in memory loss.
Leber’s hereditary optic neuropathy (LHON) has been noted to have remission associated with idebenone supplementation and/or accelerate the rate of recovery, with other case studies, open-label trials, or retrospective assessments noting benefit with supplementation. 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.
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)