Seltorexant
Selective orexin-2 (OX2R) receptor antagonist in development for insomnia and depression.
Pharmacology
Contents
WHAT IS SELTOREXANT?
Detailed overview
Seltorexant (JNJ-42847922 / MIN-202) is a selective orexin-2 (OX2R) receptor antagonist that blocks the wakefulness-promoting orexin signaling in the hypothalamus while largely sparing the orexin-1 (OX1R) receptor. This selectivity distinguishes it from dual orexin receptor antagonists (such as suvorexant and daridorexant) and is proposed to give a favorable next-day profile. In human trials it shortened the latency to persistent sleep, increased total sleep time and improved sleep maintenance, and in randomized, placebo-controlled Phase 2 and Phase 3 studies it also showed antidepressant effects, particularly in major depression accompanied by insomnia. As of 2026 it is an investigational compound and not yet approved as a medicine.
Mechanism
Selective OX2R antagonist
Half-life
~2-3 hours
Legal status
Investigational (Phase 3), not approved
Receptor profile
- Orexin-2 receptor (OX2R)Strong
- Wakefulness drive suppressionStrong
- Orexin-1 receptor (OX1R, spared)Weak
Safety
Side effects, stop signs, contraindications
Side effects · 5
- Next-day grogginess, somnolence, occasionally residual sedation
- Headache
- Mild dizziness
- Mild fatigue
- Vivid dreams or sleep paralysis theoretically possible with orexin antagonists (rare)
Contraindications · 4
- Pregnancy and breastfeeding: safety not established, avoid
- Narcolepsy or other orexin-deficient states: further blockade of orexin signaling is contraindicated
- Additive sedation with other CNS depressants (alcohol, benzodiazepines, opioids)
- Investigational compound: not an approved medicine, not for use outside clinical supervision
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
A randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity
Bonaventure P, Dugovic C, Shireman B, et al.
Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study
Savitz A, Wajs E, Zhang Y, et al.
Selective Orexin Receptor Antagonists as Novel Augmentation Treatments for Major Depressive Disorder: Evidence for Safety and Efficacy From a Phase 2B Study of Seltorexant
Recourt K, de Boer P, van der Ark P, et al.
Characteristics of Seltorexant-Innovative Agent Targeting Orexin System for the Treatment of Depression and Anxiety
Szmyd B, Karuga FF, et al.
Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial
Recourt K, et al.
FAQ
FAQ
Seltorexant is an investigational drug being studied for sleep problems and depression, particularly cases where poor sleep and depression occur together. It works by dialing down a brain signal that keeps you awake, helping you fall asleep faster and sleep more soundly. In trials it shortened time to fall asleep, improved total sleep time and mood, and was reported to be well tolerated. Important: this is still in clinical development, not an approved, marketed drug.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.