Almorexant, also known by its development code ACT-078573, is an

orexin antagonist An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one or both of the orexin receptors, OX1 and OX2. Medical applications include treatment of sleep disorders ...

, acting as a competitive

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

of the OX₁ and OX₂

orexin receptor The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (, ). Both orexin receptors exhibit ...

s, which was being developed by the pharmaceutical companies

Actelion Actelion is a pharmaceuticals and biotechnology company established in December 1997, headquartered in Allschwil near Basel, Switzerland. Actelion focuses on the manufacture of drugs that treat rare diseases and orphan diseases. Some of the dr ...

and GSK for the treatment of

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

. Development of the drug was abandoned in January 2011 due to concerns over the hepatic safety of almorexant after transient increases in liver enzymes were observed in trials.GSK and Actelion discontinue clinical development of almorexant
- GSK press release, 28 Jan 2011

Pharmacology

Pharmacodynamics

Almorexant is a competitive, dual OX₁ and OX₂ receptor antagonist and selectively inhibits the functional consequences of OX₁ and OX₂ receptor activation, such as intracellular Ca²⁺ mobilization. It dissociates very slowly from the orexin receptors and this may prolong its duration of action.

History

Originally developed by Actelion, from 2007 almorexant was being reported as a potential

blockbuster drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...

, as its novel mechanism of action (orexin receptor antagonism) was thought to produce better quality sleep and fewer side effects than the traditional

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s and

Z-drug Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive drugs that are very benzodiazepine-like in nature. They are used in the treatment of sleep proble ...

s which dominated the multibillion-dollar insomnia medication market. In 2008,

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

bought the development and marketing rights for almorexant from Actelion for an initial payment of $147 million. The deal would have been worth an estimated $3.2 billion if the drug had successfully completed clinical development and obtained FDA approval. GSK and Actelion continued to develop the drug together, and completed a Phase III

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

in November 2009. However, in January 2011 Actelion and GSK announced they were abandoning the development of almorexant because of its side effect profile.Actelion and GSK Discontinue Clinical Development of Almorexant
- Actelion press release, 28 Jan 2011

Society and culture

Names

''Almorexant'' is the generic name of the drug and its . It is also known by its former developmental code name ''ACT-078573''.

References

External links

Actelion's official website
{{Orexin receptor modulators Abandoned drugs Acetamides Norsalsolinol ethers Orexin antagonists Sedatives Trifluoromethyl compounds