Chemical Properties:Yellow-Orange Crystalline Solid
Usage:Cognition enhancer, nootropic.Ubiquinone derivative with protective effects against cerebral ischemia.
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.
Mechanisms: Idebenone (particularly its reduced form) is highly antioxidative, with IC50 values against oxidative damage in the range of 0.5-10µM.
Idebenone is an organic compound belonging to the quinone family, being similar to coenzyme Q-10. 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.
1) 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 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.
3) Glutaminergic Neurotransmission
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).
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