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Abandoned drugs
Almorexant
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Almorexant

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Almorexant
Almorexant.svg
Clinical data
Other names ACT-078573
Routes of
administration		 By mouth
Drug class Orexin antagonist
ATC code
  • None
Pharmacokinetic data
Metabolism Hepatic
Elimination half-life 13–19 Hours
Identifiers
  • (2R)-2-[(1S)- 6,7-Dimethoxy-1-{2-[4-(trifluoromethyl)phenyl]ethyl}-3,4-dihydroisoquinolin-2(1H)-yl]-N-methyl-2-phenylacetamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C29H31F3N2O3
Molar mass 512.573 g·mol−1
3D model (JSmol)
  • CNC(=O)[C@@H](C1=CC=CC=C1)N2CCC3=CC(=C(C=C3[C@@H]2CCC4=CC=C(C=C4)C(F)(F)F)OC)OC
  • InChI=1S/C29H31F3N2O3/c1-33-28(35)27(20-7-5-4-6-8-20)34-16-15-21-17-25(36-2)26(37-3)18-23(21)24(34)14-11-19-9-12-22(13-10-19)29(30,31)32/h4-10,12-13,17-18,24,27H,11,14-16H2,1-3H3,(H,33,35)/t24-,27+/m0/s1 checkY
  • Key:DKMACHNQISHMDN-RPLLCQBOSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Almorexant, also known by its development code ACT-078573, is an orexin antagonist, acting as a competitive antagonist of the OX1 and OX2orexin receptors, which was being developed by the pharmaceutical companies Actelion and GSK for the treatment of insomnia. 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.

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.

In 2008, GlaxoSmithKline 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 in November 2009.

However, in January 2011 Actelion and GSK announced they were abandoning the development of almorexant because of its side effect profile.

Society and culture

Names

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

External links


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