spec sheet11 rows
Vornorexant taisho's investigational dual orexin receptor antagonist (TS-142) with an unusually short half-life, designed for fast sleep onset and minimal next-day residual effects; in clinical development in japan.
- very short half-life aimed at minimal next-morning residual sleepiness
- rapid absorption for fast sleep onset
- active metabolites are weak and poorly brain-penetrant, so effects clear quickly
- dose-proportional pharmacokinetics in phase 1
- acute sleepiness in the hour or two after dosing (on-target)
- orexin-class theoretical cautions not yet characterized in large trials
Overview
the 'ultra-short' DORA. vornorexant is absorbed and cleared very fast (half-life around 1-3 hours in humans), which is the whole pitch: fall asleep quickly, then have the drug essentially gone by morning. still investigational; do not confuse it with takeda's TAK-861/oveporexton, which is an orexin agonist for narcolepsy, the opposite mechanism.
- vornorexant's half-life (~1-3 hours) is dramatically shorter than suvorexant's (~12 hours), taking the 'short-acting orexin blocker' idea to its logical extreme.
- its main active metabolites are weaker and barely enter the brain, so the parent drug does almost all the work; that is unusual and helps keep the next-morning burden low.
- it is easy to mix up with takeda's TAK-861 (oveporexton), but they are opposites: vornorexant blocks orexin receptors (for insomnia), TAK-861 activates OX2 receptors (for narcolepsy).
Mechanism
vornorexant is a dual receptor ; it blocks OX1R and OX2R to reduce orexin wake-drive and promote sleep, like the rest of the DORA class. its distinguishing feature is pharmacokinetic, not mechanistic: in healthy volunteers it is rapidly absorbed (tmax ~0.5-3 h) and rapidly eliminated ( ~1.3-3.3 h), with active metabolites (M1, M3) that are weaker and contribute little to central effect, so the parent compound drives efficacy (kambe 2023; konno 2024). the design intent is rapid onset for sleep initiation plus a very low next-morning residual burden; sleepiness-related pharmacodynamic measures rose at 1 and 4 hours post-dose but showed no consistent next-morning impairment in phase 1.
receptor fingerprint
OX1R (-1 / HCRTR1)competitive antagonist
OX2R (-2 / HCRTR2)competitive antagonist
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
investigational; no approved-label safety profile yet. phase 1 studies in healthy japanese adults (single and multiple ascending doses, including elderly) reported dose-proportional exposure and the expected acute sleepiness, with no consistent next-day residual effects and no major safety flags at studied doses (kambe 2023). standard orexin-class theoretical cautions (sleep paralysis, hypnagogic hallucinations, cataplexy-like weakness) would need larger trials to characterize. not available as a medicine outside trials.
History
developed by taisho pharmaceutical (japan) as TS-142/ORN-0829; phase 1 pharmacokinetic/pharmacodynamic studies were published in 2023 (kambe 2023) and preclinical metabolism/disposition work in 2024 (konno 2024), consistent with a program aimed at the japanese insomnia market where orexin antagonists (suvorexant, lemborexant) are already well established. it has not yet been approved.
Reputation
an interesting 'next-generation' short-acting DORA on the design axis that daridorexant popularized (short half-life = clean morning), pushed even further; but it is early-stage and japan-focused, so it has limited real-world track record. watch the phase 2/3 efficacy data.
Subjective profileweighing the evidence above
The very short half-life targets exactly what ruins most sleep drugs, and Phase 1 showed the expected acute sleepiness without consistent next-day residue. It is still investigational and in development only in Japan, so there is nothing to buy and no long-term profile to judge it on.
Resources
This entry is here for reference.
Research
- 1.Pharmacokinetics, pharmacodynamics and safety profile of the dual orexin receptor antagonist vornorexant/TS-142 in healthy Japanese participants following single/multiple dosing: Randomized, double-blind, placebo-controlled phase-1 studies.
- 2.Preclinical metabolism and the disposition of vornorexant/TS-142, a novel dual orexin 1/2 receptor antagonist for the treatment of insomnia.
2 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
can i buy vornorexant?
no; it is an investigational drug in clinical development (taisho, japan) and is not approved or marketed anywhere. approved orexin sleep drugs are daridorexant, lemborexant, and suvorexant.
what makes vornorexant different from other orexin blockers?
its half-life is extremely short, roughly 1-3 hours, versus ~8 hours for daridorexant and ~12 for suvorexant. the goal is fast sleep onset with almost no next-morning drug left, potentially the 'cleanest' morning of the class, though that has to be proven in larger efficacy trials.
is vornorexant the same as TAK-861?
no, and this is a common mix-up. vornorexant is an orexin receptor antagonist (blocks the receptors, for insomnia). TAK-861/oveporexton is an orexin OX2 agonist (activates the receptor, for narcolepsy). opposite mechanisms.
does it cause next-day grogginess?
in phase 1, sleepiness measures rose shortly after dosing but showed no consistent next-morning impairment, which is what the short half-life is designed to achieve. real-world next-day data await later trials.
will a very short half-life hurt sleep maintenance?
that is the open question. a short-acting drug is great for falling asleep and for a clean morning, but may cover less of the back half of the night; efficacy trials will show whether it holds sleep as well as longer-acting DORAs.
Limitations of the evidence
- unknown long-term profile; investigational
Adverse effects
- acute sleepiness in the hour or two after dosing (on-target)
- orexin-class theoretical cautions not yet characterized in large trials