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OTHERPEPTIDE PROFILE

NPY

Also known as Neuropeptide Y, NPY (human, rat), neuropeptide tyrosine

Neuropeptide Y (NPY) is a 36-amino acid neuropeptide and one of the most abundant neuropeptides in the mammalian central nervous system. It is the most potent known appetite-stimulating (orexigenic) peptide, acting predominantly in the hypothalamus. NPY also regulates stress responses, anxiety, circadian rhythms, cardiovascular function, pain perception, and bone metabolism, making it a broadly important neuromodulator.

Last updated April 10, 2026

TL;DR

Quick summary

NPY (Neuropeptide Y) is a 36-amino acid neuropeptide and the most potent known appetite-stimulating peptide in the mammalian brain. It also regulates stress responses, anxiety, and cardiovascular function, with intranasal NPY delivery showing preliminary positive results in Phase 1 PTSD studies.

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Overview

Neuropeptide Y (NPY) is a 36-amino acid neuropeptide and one of the most abundant neuropeptides in the mammalian central nervous system. It is the most potent known appetite-stimulating (orexigenic) peptide, acting predominantly in the hypothalamus. NPY also regulates stress responses, anxiety, circadian rhythms, cardiovascular function, pain perception, and bone metabolism, making it a broadly important neuromodulator.

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Mechanism of action

NPY signals through five GPCRs (Y1–Y5 in humans). Y1 and Y5 receptors in the arcuate and paraventricular nuclei of the hypothalamus mediate the primary orexigenic effects, increasing food intake and energy storage in white adipose tissue. Y2 and Y4 receptors have appetite-inhibiting roles, creating a complex regulatory balance. NPY is co-released with norepinephrine from sympathetic nerve terminals, modulating vasoconstriction and blood pressure. Chronic NPY elevation promotes adipogenesis, suppresses brown adipose tissue activation, and contributes to obesity maintenance.

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Dosing protocols

PurposeRouteDosageFrequency
appetite/feeding research (animal)intravenous110 nmol/kgper study protocol

Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.

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Research summary

NPY knockout mice on high-fat diets show reduced obesity, validating it as an obesity target. However, Y1 and Y5 receptor antagonists have largely failed in clinical trials due to off-target effects and limited efficacy. NPY's role in resilience to stress-induced depression and its anti-anxiety effects via Y1R have generated interest in NPY-based PTSD treatments. Intranasal NPY delivery has been explored in Phase 1 PTSD studies with preliminary positive results.[1][2][3][4][5]

📄This section cites 5 peer-reviewed sources. View all references →
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Evidence grading

Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.

strong
Most potent known orexigenic peptideDecades of animal studies consistently show dose-dependent food intake stimulation via hypothalamic Y1/Y5
moderate
NPY knockout mice resist diet-induced obesityMultiple transgenic mouse studies validate NPY's role in obesity maintenance on high-fat diets
moderate
Y1/Y5 antagonists failed obesity trialsClinical Phase II trials showed limited efficacy and off-target effects, ending major obesity programs
preliminary
Intranasal NPY shows PTSD signalPhase 1 PTSD studies with intranasal NPY delivery reported preliminary positive anxiolytic results
strong
Co-released with norepinephrine for vasoconstrictionEstablished cardiovascular physiology across animal and human sympathetic nerve studies

Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data

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Side effects

Vasoconstriction (high doses)
Potential pro-adipogenic effects with chronic exposure
Transient hypertension (IV research doses)

Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.

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Common stacks

Peptides commonly paired with NPY for synergistic effects.

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Sourcing & access

Research compound

NPY is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).

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Frequently asked questions

Neuropeptide Y is a 36-amino acid neuropeptide and one of the most abundant neuropeptides in the mammalian central nervous system. It is the most potent known appetite-stimulating (orexigenic) peptide, acting predominantly in the hypothalamus, and also regulates stress responses, anxiety, circadian rhythms, and cardiovascular function.

NPY signals through five GPCRs (Y1-Y5). Y1 and Y5 receptors in the hypothalamus mediate the primary appetite-stimulating effects. NPY is co-released with norepinephrine from sympathetic nerve terminals, modulating vasoconstriction and blood pressure. Chronic NPY elevation promotes fat storage and suppresses brown adipose tissue activation.

NPY is a research compound not approved for human use. In research settings, high doses can cause vasoconstriction, transient hypertension, and pro-adipogenic effects with chronic exposure. Y receptor antagonists targeting the NPY pathway are being developed as prescription drugs.

NPY has anti-anxiety effects and promotes resilience to stress-induced depression via the Y1 receptor. Intranasal NPY delivery has been explored in Phase 1 PTSD studies with preliminary positive results, making it a research target for stress-related disorders.

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Research references

  1. Regulation of Homeostasis by Neuropeptide Y: Involvement in Food IntakeChen Y, Lin YC, et al.Metabolites, 2022Review
  2. AgRP/NPY and POMC neurons in the arcuate nucleus and their potential role in treatment of obesityVarela L, Horvath TL, et al.Reviews in Endocrine and Metabolic Disorders, 2022Review
  3. Neuropeptide Y and Metabolism Syndrome: An Update on Perspectives of Clinical Therapeutic Intervention StrategiesChen H, Habedanck R, et al.Frontiers in Cell and Developmental Biology, 2021Review
  4. Physiological and Therapeutic Roles of Neuropeptide Y on Biological FunctionsBrothers SP, Bhatt S, et al.Advances in Experimental Medicine and Biology, 2019Review
  5. Agrp-negative arcuate NPY neurons drive feeding under positive energy balance via altering leptin responsiveness in POMC neuronsChen JJ, Li Z, et al.Nature Communications, 2023PubMed
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