Research Only Cognitive & Nootropic

Neuropeptide Y

also known as: NPY, Neuropeptide Tyrosine

The brain's most abundant neuropeptide — a 36-amino-acid master regulator of appetite, stress resilience, and anxiety that connects metabolic and cognitive peptide networks.

A 36-amino-acid peptide and one of the most abundant neuropeptides in the CNS, acting through Y1-Y5 receptors to powerfully stimulate appetite, reduce anxiety, enhance stress resilience, and modulate circadian rhythms and sympathetic vasoconstriction.

Mechanism of action

Binds five receptor subtypes (Y1, Y2, Y4, Y5, Y6) — all Gi/o-coupled GPCRs. Y1 activation in the amygdala produces anxiolysis. Y1/Y5 activation in the hypothalamic arcuate and paraventricular nuclei potently stimulates food intake (the strongest known orexigenic signal). Peripherally, NPY is co-released with norepinephrine from sympathetic nerves, producing potent vasoconstriction.

Primary uses

Endogenous appetite regulation (most potent known orexigenic peptide)
Stress resilience and anxiety modulation (high NPY = resilience to PTSD)
Circadian rhythm regulation
Sympathetic vasoconstriction (co-transmitter with norepinephrine)

Typical dosing

N/A N/A N/A (endogenous)

Not used therapeutically. Plasma NPY levels are studied as a PTSD resilience biomarker.

Regulatory status

Not approved as a drug. NPY receptor agonists and antagonists are under investigation for obesity (Y5 antagonists), anxiety disorders (Y1 agonists), and PTSD resilience research.

References

[pubmed] Tatemoto K, et al. "Neuropeptide Y -- a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide." Nature. 1982;296(5858):659-660.
[pubmed] Morgan CA 3rd, et al. "Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress." Biol Psychiatry. 2002;52(2):136-142.

Related peptides

Peptide YY

The postprandial 'stop eating' signal — an endogenous satiety peptide that reduces appetite via the Y2 receptor, and a pharmacological target for next-generation obesity drugs.

Ghrelin

The 'hunger hormone' — the only known circulating appetite stimulant, and the endogenous ligand that GHRP-2, GHRP-6, and MK-677 were designed to mimic.

Orexin-A

The hypothalamic wakefulness peptide — loss of orexin neurons causes narcolepsy, and blocking its receptors produced the blockbuster insomnia drugs suvorexant and lemborexant.

Cholecystokinin

The original satiety signal — a gut-brain peptide that tells you to stop eating, stimulates digestion, and modulates anxiety and pain in the CNS.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.