Orexin A
Also known as: Orexin A, Hypocretin-1
A 33-amino-acid neuropeptide produced in the lateral hypothalamus that regulates wakefulness, arousal, appetite and energy homeostasis. It is studied for its powerful promotion of alertness and sleep-wake stability.
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Mechanism of Action
Orexin A (hypocretin-1) binds both orexin receptor subtypes OX1R and OX2R, which are G-protein-coupled receptors that depolarize target neurons and increase intracellular calcium. Through OX2R it strongly stabilizes wakefulness by activating histaminergic, noradrenergic and dopaminergic arousal circuits. It also modulates feeding behavior, reward signaling and autonomic tone. Loss of orexin neurons is the underlying cause of narcolepsy type 1, which frames its central role in maintaining wakefulness.
- Half-life
- Short; on the order of minutes to roughly an hour depending on route
- Administration Routes
- intranasal, subcutaneous
- Research Status
- Research Chemical
Reported Benefits
- Strongly promotes wakefulness and arousal
- Studied for stabilizing sleep-wake transitions
- Investigated for narcolepsy-related deficits
- May enhance attention and alertness
- Modulates appetite and energy expenditure
- Explored for cognitive and reward signaling
Potential Side Effects
- Insomnia or disrupted sleep if administered late in the day
- Increased heart rate and blood pressure
- Anxiety or agitation
- Appetite changes
Common Dosing
Human and animal research has primarily used intranasal administration in microgram amounts; defined research dosing is not standardized. Provided for research-use-only context and not as personal medical advice.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- Cardiovascular disease due to potential pressor and heart-rate effects
- Anxiety or insomnia disorders
- Pregnancy and breastfeeding due to lack of data
- View
Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior
1998
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Systemic and nasal delivery of orexin-A (Hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates
2007
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Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior
1998
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Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy
2011
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The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy
2014