INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...
), also known by its development code ACT-078573, is an orexin antagonist, acting as a competitive
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.orexin receptors, which was being developed by the pharmaceutical companies
Actelion
Actelion Pharmaceuticals Ltd. is a pharmaceuticals and biotechnology company established in December 1997, headquartered in Allschwil near Basel, Switzerland. The company is part of Johnson & Johnson Innovative Medicine business segment.
Actel ...
insomnia
Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
. 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.
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
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...
.
History
Originally developed by Actelion, from 2007 almorexant was being reported as a potential
blockbuster drug
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, 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 ...
, 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), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...
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, depressant, sedative, hypnotic, anxiolytic drugs that are benzodiazepine-like in uses, such as f ...
s which dominated the multibillion-dollar insomnia medication market.
In 2008,
GlaxoSmithKline
GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...
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 subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
in November 2009.
However, in January 2011 Actelion and GSK announced they were abandoning the development of almorexant because of its side effect profile.
In 2014 researchers from Actelion published work indicating that almorexant had mild abuse potential but significantly less abuse potential than
zolpidem
Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and after beh ...