spec sheet11 rows
Almorexant actelion's dual orexin receptor antagonist and the first DORA to reach late clinical trials for insomnia; development was halted in 2011 over tolerability/safety concerns, but it proved the concept and is still used as a research tool.
- proved in humans that dual orexin block promotes sleep, opening the entire class
- useful reference DORA in preclinical sleep, depression, and addiction research
- on-target sedation and orexin-class risks (theoretical sleep paralysis, hallucinations, cataplexy-like effects)
Overview
the trailblazer that didn't make it. almorexant showed that blocking both orexin receptors reliably promotes sleep in humans, but actelion and gsk pulled it in phase 3 citing tolerability/safety findings; it never reached market. today it mostly lives on in lab studies as a reference DORA.
- almorexant was the first dual orexin antagonist to reach phase 3, years before suvorexant became the first approved one.
- actelion discontinued it in 2011 over tolerability/safety concerns that were never fully published, which is unusual and made the field warier about long-term orexin blockade.
- it is still one of the most-cited 'tool' DORAs in preclinical orexin research, including studies of depression and addiction.
Mechanism
almorexant is a competitive dual receptor ; it blocks OX1R and OX2R with roughly balanced, low-nanomolar potency, cutting orexin-a/orexin-b drive to the arousal network and promoting the transition to sleep, particularly rem and non-rem in preclinical models. mechanistically it is the template the whole DORA class followed. its clinical failure was not about efficacy (it worked as a hypnotic) but about the tolerability/safety profile that emerged in longer trials, which the company did not disclose in full when it discontinued the program; the episode made the field more cautious about long-term orexin blockade and shaped how suvorexant and daridorexant were later designed and dosed.
receptor fingerprint
OX1R (-1 / HCRTR1)competitive antagonist
OX2R (-2 / HCRTR2)competitive antagonist
Dosingtypical ranges, not medical advice
interested in protocols and clinical dosages? make an account to see them! ^_^
Safetyrisks and cautions, not medical advice
development was discontinued in 2011 for tolerability/safety reasons that were not fully published; because it never completed development there is no approved-label safety profile. in trials it produced the expected on-target effects (sleepiness, and orexin-class risks like potential for sleep paralysis/hallucinations/cataplexy-like effects at high exposure). it is investigational-only and not available as a medicine; treat any use as research.
History
developed by actelion (later partnered with gsk) as ACT-078573; it was the first DORA to advance into phase 3 for primary insomnia. actelion halted development in 2011, citing tolerability/safety findings, ending a high-profile program and briefly casting doubt on the class before merck's suvorexant revived it. almorexant remains a heavily cited reference compound in orexin pharmacology and has been used in preclinical depression, addiction, and sleep models (fagan 2022).
Reputation
remembered as the pioneer that proved the mechanism but stumbled on safety/tolerability; among researchers it is a standard tool DORA, but it has no clinical standing and is not a therapy. its cautionary story is part of why the approved orexin drugs are dosed conservatively.
Subjective profileweighing the evidence above
Historically important and practically unavailable. It proved dual orexin blockade works as a hypnotic and opened the whole class, then was halted in 2011 over tolerability and safety findings that were never published. If the mechanism appeals, use an approved DORA instead.
Resources
This entry is here for reference.
Research
- 1.Orexin Receptor Antagonists in the Treatment of Depression: A Leading Article Summarising Pre-clinical and Clinical Studies.
- 2.A Comprehensive Review of Lemborexant to Treat Insomnia.
2 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
can i get almorexant as a sleep medicine?
no. its development was stopped in 2011 and it was never approved anywhere; it exists only as an investigational/research compound. if you want an approved orexin sleep drug, that is daridorexant, lemborexant, or suvorexant.
why was almorexant discontinued?
actelion (with gsk) halted the phase 3 program in 2011 citing tolerability/safety concerns. the specifics were never fully published, which is part of why the story is notable; efficacy as a hypnotic was not the problem.
was almorexant effective for insomnia?
yes, in trials it worked as a hypnotic and promoted sleep, which is exactly why it validated the orexin approach. the class only reached patients later, through suvorexant (2014).
is almorexant an OX1 or OX2 blocker?
both; it is a dual orexin receptor antagonist (DORA) with roughly balanced OX1R/OX2R blockade, the same basic mechanism as the approved orexin drugs.
does almorexant still matter?
as a research tool, yes; it is a standard reference DORA in preclinical work on sleep, mood, and addiction. as a treatment, no.
Limitations of the evidence
- unpublished tolerability/safety findings led to discontinuation
Adverse effects
- on-target sedation and orexin-class risks (theoretical sleep paralysis, hallucinations, cataplexy-like effects)