Idebenone [2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone] is a *synthetic analogue* of a naturally occuring product, coenzyme Q10 (CoQ10), a cofactor, membrane antioxidant, and essential constituent of the ATP-producing mitochondrial electron transport chain.
Idebenone is a potent antioxidant, with the ability to operate under low oxygen tension situations. Because of its ability to inhibit lipid peroxidation (read: phosopholid attack by free radical products from normal cell oxidation that occurs under exercise conditions), idebenone protects cell membranes and mitochondria from oxidative damage. Its antioxidant properties protect against cerebral ischemia and nerve damage in the central nervous system. . This compound has also been shown to stimulate nerve growth factor, a characteristic that could be important in the treatment of Alzheimer's and other neurodegenerative diseases.
Biochemistry and Pharmacokinetics
Idebenone is rapidly absorbed and reaches peak concentrations in the brain comparable to those in plasma. Animal studies showed a peak plasma level 15 minutes after oral administration, with a half-life of 2.2-15.4 hours. Idebenone was well distributed in tissues, with higher concentrations in the gut, liver, and kidney. Excretion was via both urine and feces, mostly as metabolites. A human pharmacokinetic and safety study found a half-life of 18 hours, with biphasic elimination. Researchers found no long-term tissue accumulation in humans or rats.
Mechanisms of Action
As with other antioxidants, idebenone exists in a reduced and an oxidized state. In a study of idebenone's effect on astroglial cells, idebenone, in either redox state, significantly inhibited the enzymatic metabolism of arachidonic acid by cyclooxygenase and lipoxygenase (most important enzymes in the prostanoid biosynthesis pathway). This effect was stronger with the reduced form, and showed potential central nervous system anti-inflammatory activity.
Introduction of iron and ascorbate to a cell mixture or a group of isolated ceils can establish experimental cellular oxidant injury. Synaptosomes isolated from rat brain cortex were treated with iron and ascorbate. Idebenone prevented both the formation of reactive oxygen species in the cytosol and mitochondria, as well as a decrease in protein-sulfhydryl content (an indicator of protein oxidation), compared to controls.
As with its parent compound, CoQ10, idebenone functions as an electron carrier within the membrane bound electron transport chain of inner mitochondrial membranes and inhibits mitochondrial lipid peroxidation, thus protectingmitochondrial against oxidative membrane damage. This would be particularly important for heart, liver, lungs, and brain mitochondrial functional and structural integrity. Extra brownie points here - it acts in the same manner as milk thistle (hint hint).
Idebenone treatment of rats with experimental cerebral ischemia inhibited the loss of acetylcholine in forebrain regions, prevented increases in lactate and free fatty acids, and preserved ATP content in the cerebral cortex. These results indicate idebenone protects against ischemic damage and promotes ATP production in the brain.
As with all patented drugs, this one was developed with an eye towards certain disease states, including stroke, parkinsons, cardiovascular infact recovery and liver disease.
Liver Disease: Oxidative stress has been implicated in a number of hepatic diseases, including bile acid-induced liver injury in hepatic cholestasis, which was evaluated in an in vitro study. Treatment with idebenone protected against bile acid-induced rat hepatocellular injury and lipid peroxidation, and prevented hydroperoxide production in hepatic mitochondria.
See also (and note comments about its function as an SRRI and anti depressant - also controls anger, and compulsive obsessive disorders).