Idebenone, sold under the brand name Raxone among others, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

that was initially developed by

Takeda Pharmaceutical Company The is a Japanese multinational pharmaceutical company. It is the third largest pharmaceutical company in Asia, behind Sinopharm and Shanghai Pharmaceuticals, and one of the top 20 largest pharmaceutical companies in the world by revenue (t ...

for the treatment of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

and other

cognitive Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

defects. This has been met with limited success. The Swiss company Santhera Pharmaceuticals has started to investigate it for the treatment of

neuromuscular diseases A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junctions, or skeletal muscles, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and we ...

. In 2010, early

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s for the treatment of

Friedreich's ataxia Friedreich's ataxia (FRDA) is a rare, inherited, autosomal recessive neurodegenerative disorder that primarily affects the nervous system, causing progressive damage to the spinal cord, peripheral nerves, and cerebellum, leading to impaired ...

and

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy predominantly affecting boys. The onset of muscle weakness typically begins around age four, with rapid progression. Initially, muscle loss occurs in the thighs and pe ...

have been completed. the drug is not approved for these indications in North America or Europe. It is approved by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) for use in

Leber's hereditary optic neuropathy Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; it predomin ...

(LHON) and was designated an

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

in 2007. Chemically, idebenone is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

of the

quinone The quinones are a class of organic compounds that are formally "derived from aromatic compounds benzene.html" ;"title="uch as benzene">uch as benzene or naphthalene] by conversion of an even number of –CH= groups into –C(=O)– groups with ...

family. It is also promoted commercially as a Organic compound#Synthetic compounds, synthetic

analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...

of coenzyme Q₁₀ (CoQ₁₀).

Uses

Indications that are or were approved in some territories

Nootropic effects and Alzheimer's disease

Idebenone improved learning and memory in experiments with mice. In humans, evaluation of

Surrogate endpoint In clinical trials, a surrogate endpoint (or surrogate marker) is a Outcome measure, measure of effect of a specific treatment that may correlate with a ''real'' clinical endpoint but does not necessarily have a guaranteed relationship. The Nationa ...

s like

electroretinography Electroretinography measures the electrical responses of various cell types in the retina, including the Photoreceptor cell, photoreceptors (rod cell, rods and cone cell, cones), inner retinal cells (Retinal bipolar cell, bipolar and amacrine ce ...

auditory evoked potential An evoked potential or evoked response is an electrical potential in a specific pattern recorded from a specific part of the nervous system, especially the brain, of a human or other animals following presentation of a stimulus such as a light fl ...

s and

visual analogue scale The visual analogue scale (VAS) is a psychometric response scale that can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. When responding to a VAS item, respond ...

s also suggested positive

nootropic Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...

effects, but larger studies with hard endpoints are missing. Research on idebenone as a potential therapy of

have been inconsistent, but there may be a trend for a slight benefit. In May 1998, the approval for this indication was cancelled in Japan due to the lack of proven effects. In some European countries, the drug is available for the treatment of individual patients in special cases.

Friedreich's ataxia (Sovrima)

Preliminary testing has been done in humans and found idebenone to be a safe treatment for Friedreich's ataxia (FA), exhibiting a positive effect on

cardiac hypertrophy Ventricular hypertrophy (VH) is thickening of the walls of a ventricle (lower chamber) of the heart. Although left ventricular hypertrophy (LVH) is more common, right ventricular hypertrophy (RVH), as well as concurrent hypertrophy of both ventr ...

and neurological function. The latter was only significantly improved in young patients. In a different experiment, a one-year test on eight patients, idebenone reduced the rate of deterioration of cardiac function, but without halting the progression of

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

. The drug was approved for Friedreich's ataxia in Canada in 2008 under conditions including proof of efficacy in further clinical trials. However, in February 2013, Health Canada announced that idebenone would be voluntarily recalled as of April 2013 by its Canadian manufacturer, Santhera Pharmaceuticals, due to the failure of the drug to show efficacy in the further clinical trials that were conducted. In 2008, the

(EMA) refused a marketing authorisation for this indication. As of 2013 the drug was not approved for FA in Europe nor in the US, where, as of February 2023, there is only one approved treatment.

Leber's hereditary optic neuropathy (Raxone)

(LHON) is a mitochondrially inherited (mother to all offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. Santhera completed a Phase III clinical trial in this indication in Europe with positive results, and submitted an application to market the drug to European regulators in July 2011. It is approved by EMA for this indication and was designated an

in 2007.

Indications being explored

Duchenne muscular dystrophy (Catena)

After experiments in mice and preliminary studies in humans, idebenone has entered Phase II clinical trials in 2005 and Phase III trials in 2009.

Other neuromuscular diseases

Phase I and II clinical trial for the treatment of

MELAS Melas may refer to: People * Melas (mythology), a number of different characters in Greek mythology * Melas, an Ancient Greek first name. Its most notable holders were Melas the Elder and Younger, two tyrants of Ephesus whose dynasty intermarried ...

(mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) was conducted. Phase I/II trial for primary progressive multiple sclerosis concluded that Idebenone did not inhibit disability progression. As of 2022, a phase III clinical trial is ongoing for the treatment of

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

Life style

Idebenone is claimed to have properties similar to CoQ₁₀ in its

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

properties, and has therefore been used in

anti-aging The anti-aging movement is a social movement devoted to eliminating or reversing aging, or reducing the effects of it. A substantial portion of the attention of the movement is on the possibilities for life extension, but there is also interest i ...

on the basis of

free-radical theory The free radical theory of aging states that organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell.Erbas M, Sekerci H. "Importance of Free ...

. Clinical evidence for this use is missing. It has been used in

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

applications to treat

wrinkle A wrinkle, also known as a rhytid, is a fold, ridge or crease in an otherwise smooth surface, such as on skin or fabric. Skin wrinkles typically appear as a result of ageing processes such as glycation, habitual sleeping positions, loss of b ...

Pharmacology

In cellular and tissue models, idebenone acts as a transporter in the

electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

and thus increases the production of

adenosine triphosphate Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...

(ATP) which is the main energy source for cells, and also inhibits lipoperoxide formation. Positive effects on the energy household of mitochondria has also been observed in animal models. Clinical relevance of these findings has not been established.

Pharmacokinetics

Idebenone is well absorbed from the gut but undergoes excessive first pass metabolism in the liver, so that less than 1% reach the circulation. This rate can be improved with special formulations (

suspension Suspension or suspended may refer to: Science and engineering * Car suspension * Cell suspension or suspension culture, in biology * Guarded suspension, a software design pattern in concurrent programming suspending a method call and the calling ...

s) of idebenone and by administering it together with fat food; but even taking these measures

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

still seems to be considerably less than 14% in humans. More than 99% of the circulating drug are bound to

plasma protein Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other b ...

s. Idebenone metabolites include

glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucu ...

s and

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

s, which are mainly (~80%) excreted via the urine.

References

{{Authority control Antioxidants Phenol ethers Primary alcohols 1,4-Benzoquinones Orphan drugs