Orexin A
Hypocretin-1
The wakefulness neuropeptide.
Half-life
~ short
Mol. weight
3562.6 g/mol (approx, disulfide-bonded dimer)
Sequence
33-amino-acid neuropeptide (two disulfide bonds)
Discussions
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Overview
An endogenous neuropeptide produced in the hypothalamus (also called hypocretin-1) that is the master regulator of wakefulness and arousal. Orexin neurons excite the brain's arousal systems; their loss causes narcolepsy. Orexin A is researched as the most direct pharmacological handle on the wakefulness system.
Mechanism of action
Orexin A is produced by a small cluster of neurons in the lateral hypothalamus and acts on orexin-1 and orexin-2 (OX1R/OX2R) receptors throughout the brain. It excites the major arousal systems — the locus coeruleus (norepinephrine), raphe (serotonin), tuberomammillary nucleus (histamine), and others — to sustain wakefulness and stabilize the wake state. The clearest proof of its role is narcolepsy: loss of orexin neurons causes the sleep disorder, establishing orexin as the brain's master wakefulness switch.
Researched benefits
- Master regulator of wakefulness and arousal
- Directly linked to narcolepsy pathology
- Stabilizes the wake state via multiple arousal systems
Considerations
- Very short half-life; crosses blood-brain barrier poorly
- Not approved for human use
- Wakefulness modulation carries cardiovascular considerations
Key Academic Literature & Studies
Search more in PubMedPeer-reviewed citations and clinical trials evaluating Orexin A in scientific literature.
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