Cognitive & neuroEvidence B2 cited

Neuropeptide Y

aka NPY · Neuropeptide Y · PYY family

A 36-amino acid neuropeptide associated with stress resilience and longevity. Higher NPY levels found in centenarians and Special Forces soldiers with superior stress performance.

Molecular wt

4272g/mol

Formula

C189H285N55O57S

Half-life

24 min

clinical

Tmax

30 min

Route

Subcutaneous injection

PubChem

24868177

Sequence

One-letter36 residues

YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY

Three-letter

Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu-Asp-Ala-Pro-Ala-Glu-Asp-Met-Ala-Arg-Tyr-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu-Ile-Thr-Arg-Gln-Arg-Tyr-NH2

Read this before quoting the sequence

Mature human NPY is 36 residues with an obligatory C-terminal tyrosine amide (Tyr36-NH2), produced by cleavage of pro-neuropeptide Y (UniProt P01303) at residues 29-64 followed by amidation at the Gly-Lys-Arg signal. The amide is required for receptor activity. Porcine NPY differs at position 17 (Leu instead of Met) - do not use porcine values for human NPY.

Source ↗

Mechanism of action

Neuropeptide Y acts through Y1, Y2, Y4, and Y5 receptors distributed throughout the central and peripheral nervous systems. In the CNS, NPY is anxiolytic (Y1 receptor), promotes stress resilience, regulates appetite (Y1/Y5 in hypothalamus), and has anticonvulsant properties. NPY also promotes neurogenesis in the hippocampus, modulates circadian rhythm, and has vasoconstrictive effects peripherally. Higher endogenous NPY levels are associated with exceptional longevity.

What the evidence actually shows

Grade B

Strong epidemiological association between NPY levels and stress resilience/longevity. Centenarian studies show elevated NPY. Limited interventional data in humans. Animal studies support anxiolytic and neurogenic effects.

Regulatory status

Status

Not approved as a medicine in any jurisdiction.

Clinical stage

Early-phase human research only; the identified controlled trial enrolled 30 patients (PMID 33009815).

Source ↗

Pharmacokinetics

Half-life

24 min

Tmax

30 min

Absorption

subcutaneous

Elimination

renal

Washout

1 days

Low-confidence pharmacokinetics

These figures are recorded as clinical rather than measured in a published PK study. Treat them as an order of magnitude. Anything downstream of them — accumulation, steady state, washout — inherits that uncertainty.

Dosing — what backs each figure

Neuropeptide Y has been given to humans only in a single-ascending-dose crossover study: intranasal doses from 1.4 mg up to 9.6 mg, one dose per treatment day, in 26 patients with PTSD. There is no approved product, no repeat-dosing regimen and no established therapeutic dose.

ClinicalApproved labelling or a published human trial

Single ascending intranasal doses of 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6) and 9.6 mg (n=6); each participant received NPY and placebo on separate days one week apart, crossover, double-blind. Well tolerated up to and including 9.6 mg
26 randomised patients with posttraumatic stress disorder (24 completers) · intranasal
Sayed S et al. A randomized dose-ranging study of neuropeptide Y in patients with posttraumatic stress disorder. Int J Neuropsychopharmacol 2018;21:3-11 ↗

No established human dose

No approved label or completed human trial establishes a dosing regimen for this compound. Anything presented as a standard protocol for it — anywhere — is someone's convention rather than a finding.

Handling and storage

No compound-specific stability data exists

No peer-reviewed or regulatory stability data specific to NPY was located. There is no approved product and no label. Only generic lyophilised-peptide handling guidance exists. General peptide handling still applies — reconstitute gently, keep it cold, keep it dark — but any specific figure you see quoted for this compound elsewhere is someone's assumption, not a measurement.

→ Reconstitution walkthrough → Reconstitution calculator

Safety

References (2)

Mathe AA, Michaneck M, Berg E, Charney DS, Murrough JW. (2020) A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder ↗
Int J NeuropsychopharmacolPMID 33009815DOI
Thirty patients with major depressive disorder on a stable antidepressant dose insufflated 6.8 mg of NPY or placebo. Described by the authors as the first controlled trial of NPY as a treatment for MDD.
Tatemoto K. (1982) Neuropeptide Y: complete amino acid sequence of the brain peptide ↗
Proc Natl Acad Sci U S APMID 6957876DOI
Original isolation and complete sequence determination of neuropeptide Y from brain.

Data provenance

Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.

Could not verify
casNumber, storage.lyophilized, storage.reconstituted, storage.lightSensitive, reconstitution.solvent, regulatory.wada

Research use only

This profile is educational reference material. It is not medical advice, not a prescription, and not an endorsement of self-administration. Compounds discussed here are research chemicals and most are not approved for human therapeutic use.

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