Almorexant
Orexin antagonist compound
From Wikipedia, the free encyclopedia
Almorexant (INN), also known by its development code ACT-078573, is an orexin antagonist, acting as a competitive antagonist of the OX1 and OX2 orexin receptors, which was being developed by the pharmaceutical companies Actelion and GSK for the treatment of insomnia.[3] 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.[4][5]
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| Other names | ACT-078573 |
| Routes of administration | By mouth |
| Drug class | Orexin antagonist |
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| Metabolism | Hepatic |
| Elimination half-life | 13–19 hours[1][2] |
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| Formula | C29H31F3N2O3 |
| Molar mass | 512.573 g·mol−1 |
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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.[6]
History
Originally developed by Actelion, from 2007 almorexant was being reported as a potential blockbuster drug, as its novel mechanism of action (orexin receptor antagonism) was thought to produce better quality sleep and fewer side effects than the traditional benzodiazepines and Z-drugs which dominated the multibillion-dollar insomnia medication market.[7]
In 2008, GlaxoSmithKline bought the development and marketing rights for almorexant from Actelion for an initial payment of $147 million.[8] The deal would have been worth an estimated $3.2 billion if the drug had successfully completed clinical development and obtained FDA approval.[9] GSK and Actelion continued to develop the drug together, and completed a Phase III clinical trial in November 2009.[10]
However, in January 2011 Actelion and GSK announced they were abandoning the development of almorexant because of its side effect profile.[4][11]
In 2014 researchers from Actelion published work indicating that almorexant had mild abuse potential but significantly less abuse potential than zolpidem.[12]