Head to head
Oveporexton against Orexin-A
The neuropeptide and the approved drug that copies it. Oveporexton is an oral orexin receptor 2 agonist approved in August 2026 for narcolepsy type 1; orexin-A is sold as a nasal spray on a primate study, with only small crossover human data in narcolepsy.
Column A
OveporextonOveporexton (TAK-861), oral orexin receptor 2 selective agonist
An oral orexin receptor 2 agonist, not a peptide, approved by the FDA on 5 August 2026 for narcolepsy type 1 in adults. In two 12 week phase 3 trials totalling 273 people it lengthened time awake on the Maintenance of Wakefulness Test by 14 to 20 minutes against roughly no change on placebo; a majority of treated participants developed insomnia and urinary frequency.
Column B
Orexin-AOrexin-A (hypocretin-1)
The wakefulness neuropeptide, sold as a nasal spray for alertness after a primate study showed intranasal delivery reversed sleep-deprivation deficits; the only human data are small crossover studies in narcolepsy, and approved narcolepsy drugs use small molecules instead.
Side by side, on the facts we can check
| Attribute | Oveporexton | Orexin-A |
|---|---|---|
| Category | Nootropic & CNS | Nootropic & CNS |
| FDA status | FDA approved 5 August 2026 (Orzeyful, NDA 220860, orphan designation, priority review) for narcolepsy type 1 in adults. Controlled substance schedule pending DEA review at the time of labelling. | Not approved |
| Half-life | Approximately 23.2 hours | Short |
| Molecular weight | 520.51 Da (small molecule, C23H25F5N2O4S) | 3,561.1 Da |
| Mechanism | In people with narcolepsy type 1 the hypothalamic neurons that make orexin-A and orexin-B are lost, so both orexin peptides are deficient while their receptors remain. Oveporexton is a selective agonist at orexin receptor 2 (OX2R), the receptor most tied to maintaining wakefulness, and it restores signalling at that receptor without replacing the peptide. The FDA label describes the mechanism in narcolepsy as presumed to be OX2R agonism rather than proven, which is the usual wording for a receptor agonist. Human pharmacokinetics, from the label: peak plasma concentration at a median 1.5 hours, terminal half-life about 23.2 hours, protein binding above 96 percent, elimination mainly by CYP3A4 metabolism with 80.5 percent of a radiolabelled dose recovered in faeces. Strong CYP3A inhibitors raise exposure about 7 fold and are contraindicated; moderate inhibitors require a dose reduction to 0.5 mg twice daily. The urinary adverse effects are described on the label as consistent with OX2R agonism, since orexin signalling also acts on bladder control. | Agonism of hypothalamic orexin receptors OX1R and OX2R promoting wakefulness and arousal. |
| Human studies cited | 6 | 1 |
| Legal status, US | FDA-approved, prescription only | Not approved; sold 'for research use only' |
Frequently asked questions
What is the difference between Oveporexton and Orexin-A?
Oveporexton: An oral orexin receptor 2 agonist, not a peptide, approved by the FDA on 5 August 2026 for narcolepsy type 1 in adults. In two 12 week phase 3 trials totalling 273 people it lengthened time awake on the Maintenance of Wakefulness Test by 14 to 20 minutes against roughly no change on placebo; a majority of treated participants developed insomnia and urinary frequency. Orexin-A: The wakefulness neuropeptide, sold as a nasal spray for alertness after a primate study showed intranasal delivery reversed sleep-deprivation deficits; the only human data are small crossover studies in narcolepsy, and approved narcolepsy drugs use small molecules instead.
Which has stronger research evidence, Oveporexton or Orexin-A?
This database does not grade compounds. It counts what was run in people: 6 of the 9 studies cited on the Oveporexton profile were human work, against 1 of 2 for Orexin-A. Those counts are of our own citation lists and understate any larger literature, and neither is a recommendation.
Are Oveporexton and Orexin-A FDA-approved?
Oveporexton: FDA approved 5 August 2026 (Orzeyful, NDA 220860, orphan designation, priority review) for narcolepsy type 1 in adults. Controlled substance schedule pending DEA review at the time of labelling.. Orexin-A: Not approved.
Reviewed Sep 2026. This page sets two published records side by side. It is educational, it is not medical advice, and it contains no dosing protocols or recommendations for personal use.