Neuropeptide EI (NEI)
The short peptide made alongside melanin-concentrating hormone — it triggers LH release and shapes grooming and anxiety behaviour. A research neuropeptide, not a drug
Neuropeptide EI, or NEI, is a small amidated brain peptide — named for the glutamic acid (E) and isoleucine (I) at its ends — that is cut from the same precursor protein as melanin-concentrating hormone (MCH). That precursor, prepro-MCH, is best known for producing MCH, the peptide that drives feeding; NEI sits beside it and is made and released from the very same neurons, clustered in the lateral hypothalamus and zona incerta and sending fibres throughout the brain. For years NEI was the far less studied of the two, but research has mapped out several distinct jobs. It stimulates the release of luteinizing hormone (LH), the reproductive signal, by acting on gonadotropin-releasing-hormone neurons and directly on the pituitary. It shapes behaviour: injected into the brain it induces grooming and locomotor activity through dopamine and noradrenaline (specifically beta-1 adrenergic) pathways, and placed in the amygdala it produces anxiety-like behaviour. And the longer combined peptide NEI-MCH (a piece of the precursor containing both) is a protease-resistant 'superagonist' that boosts feeding more durably than MCH itself. NEI's own receptor has not been pinned down. NEI is studied as a research neuropeptide; it is not an approved medicine and has not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Neuropeptide EI is an endogenous prepro-MCH-derived peptide that has never been given to people as a treatment. The work is in animals and cells, where NEI is injected into the brain at experimental amounts that do not carry over to people.
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What is it?
Prepro-melanin-concentrating hormone (prepro-MCH) is a precursor protein best known for yielding MCH, a 19-amino-acid peptide central to feeding behaviour. The same precursor is processed into other peptides, the best characterised of which is neuropeptide EI (NEI) — a short amidated peptide named for its N-terminal glutamic acid and isoleucine. NEI and MCH are made in and released from the same neurons, concentrated in the lateral hypothalamic area and the zona incerta, whose fibres reach across the brain, and the two peptides are extensively co-localised; NEI was first confirmed as a real, secreted peptide in cultured hypothalamic cells, where its release (like MCH's) is stimulated by cyclic nucleotides and glucocorticoids.
NEI's clearest neuroendocrine role is in reproduction. Given into the brain of male and female rats it raises blood levels of luteinizing hormone (LH), the pituitary signal that governs the reproductive cycle. The anatomy fits: NEI fibres richly innervate reproduction-related regions and lie close to gonadotropin-releasing-hormone (GnRH) neurons and their terminals in the median eminence, and NEI can both modulate those GnRH neurons and act directly on the pituitary gonadotropes, so it may trigger LH release through several converging routes.
NEI also shapes behaviour. Injected into the cerebral ventricles it induces vigorous grooming and increases locomotor activity, effects that depend on dopaminergic (A-10) and noradrenergic signalling — specifically, blocking the beta-1 adrenergic receptor prevents NEI-induced grooming, and beta-1 agonists mimic it. Placed directly in the basolateral amygdala, NEI reduces the time animals spend in the open arms of an elevated-plus maze, an anxiety-like (anxiogenic) effect that, interestingly, occurs without changing stress-hormone (corticosterone) levels. NEI also interacts with the dopamine D1 receptor in the striatum at high concentrations.
A related molecule is worth noting. The longer fragment of the precursor spanning both peptides, pro-MCH(131-165) or 'NEI-MCH', is a more potent and longer-lasting stimulant of feeding than MCH alone — not because it binds the MCH receptors more tightly (it actually binds a little less well) but because it resists the enzymes that quickly break MCH down. NEI-MCH was described as the first natural MCH-receptor 'superagonist'. NEI's own receptor, by contrast, has not been identified, and much of its signalling is inferred from the neurotransmitter systems it recruits.
NEI is an endogenous prepro-MCH-derived research neuropeptide. No published study has given NEI to people as a treatment — the work is in animals and cells — it is approved nowhere, and material sold online as 'neuropeptide EI' is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says about the peptide.
Mechanism of Action
NEI is a short amidated peptide cut from prepro-MCH, co-made and co-released with MCH in lateral-hypothalamic and zona-incerta neurons. It stimulates luteinizing-hormone release (via GnRH neurons and the pituitary) and shapes behaviour — grooming and locomotion through dopaminergic/beta-1-adrenergic systems, and anxiety from the amygdala — through a receptor that has not been identified.
Prepro-MCH processing
NEI is generated by cleavage of prepro-MCH, co-made and co-secreted with MCH from the same hypothalamic neurons (PMIDs 18456371, 1327720); its own receptor is not established.
Luteinizing-hormone release
NEI raises serum LH by acting on GnRH neurons and terminals and directly on pituitary gonadotropes (PMIDs 15501532, 17016031).
Behaviour (grooming, locomotion, anxiety)
Central NEI induces grooming and locomotion via dopaminergic/beta-1-adrenergic systems (PMID 17537427) and produces anxiety-like behaviour from the amygdala, independent of the HPA axis (PMID 21164371).
Published Research
These are studies of neuropeptide EI read from their PubMed abstracts on November 6, 2026. They include a review of NEI's anatomy, function and regulation, animal studies of its stimulation of LH release and of its anxiety-like and grooming behaviours (and the adrenergic systems behind them), and a cell study confirming its secretion alongside MCH. NEI has not been given to people as a treatment; the evidence is animal and cell work.
Anatomy, function and regulation of NEI
A review of neuropeptide EI, produced by cleavage of prepro-MCH (probably amidated at its C-terminal glycine). NEI and MCH are extensively co-localised throughout the central nervous system, and NEI is also present in peripheral tissues. Beyond hormone release, NEI regulates grooming behaviour and locomotor activity; it stimulates luteinizing hormone (and, less, FSH) from pituitary cells, acts directly on gonadotropes and on GnRH neurons, and releases LH from the median eminence (a review).
NEI increases serum LH in male and female rats
Neuropeptide EI injected into the cerebral ventricles increased serum luteinizing-hormone levels in normal male rats and in chronically ovariectomised female rats primed with estrogen and a low dose of progesterone, compared with cerebrospinal-fluid controls. The authors note a likely inter-relationship between NEI, MCH and alpha-MSH, and raise the question of which receptors NEI uses (a preclinical result).
NEI induces LH secretion via multiple pathways
Mapping NEI in the female rat forebrain across the estrous cycle, NEI-immunoreactive fibres densely innervated reproduction-related regions (organum vasculosum, anteroventral periventricular nucleus, median eminence) and lay in close apposition to GnRH neurons and terminals. The anatomy suggests NEI can raise LH by direct median-eminence release, by modulating GnRH neurons or terminals, or by acting on other neurons — multiple converging routes (a preclinical result).
NEI in the amygdala induces anxiety-like behaviour
Bilateral microinjection of neuropeptide EI into the basolateral amygdala of male rats significantly decreased the time spent in the open arms of an elevated-plus maze (an anxiogenic effect) without changing locomotor activity, and without altering serum corticosterone — suggesting the anxiety-like effect of NEI is independent of the hypothalamic-pituitary-adrenal axis (a preclinical result).
Beta-1 adrenoceptors mediate NEI-induced grooming
Intracerebroventricular NEI induces excessive grooming via dopaminergic (A-10) and noradrenergic systems. The non-selective beta-blocker propranolol and the beta-1-selective metoprolol blocked NEI-induced grooming dose-dependently, while alpha- and beta-2-antagonists did not, and beta-1 agonists (isoproterenol, dobutamine) reproduced the behaviour — implicating the beta-1 adrenoceptor in NEI's neuromodulatory behavioural effect (a preclinical result).
NEI is secreted alongside MCH (first demonstration)
Cultured neonatal rat hypothalamic cells secreted both MCH and the MCH-precursor-derived peptide NEI for up to 22-24 days, confirmed by HPLC and radioimmunoassay to match the predicted sequences. Secretion of both was stimulated 3- to 5-fold by cyclic-nucleotide analogues, and dexamethasone raised their cell content — the first demonstration of the predicted NEI peptide in a biological system (a cell study).
No Established Human Dose
Neuropeptide EI is an endogenous prepro-MCH-derived peptide that has never been given to people as a treatment. The work is in animals and cells, where NEI is injected into the brain at experimental amounts that do not carry over to people. No regulator has approved any dose, and no published human dose exists, so no amount is printed here.
What this rests on: PMID 15501532, PMID 21164371, PMID 17537427.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Neuropeptide EI (NEI) is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Neuropeptide EI (NEI) has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Neuropeptide EI (NEI), before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Neuropeptide EI (NEI) stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Neuropeptide EI (NEI). What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans as a drug; an endogenous neuropeptide. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Neuropeptide EI (NEI). Results reported in the studies are under Published Research.
Source: half-life: PMID 18456371.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered NEI to people; In animals, central NEI raises LH and induces grooming, locomotion and anxiety-like behaviour (PMIDs 15501532, 17537427, 21164371) — preclinical signals, not a human safety profile; NEI's own receptor is not identified, so its mechanism is inferred from the systems it recruits (PMID 18456371); Material sold online as 'neuropeptide EI' is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Neuropeptide EI (NEI). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Neuropeptide EI is a research peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of Neuropeptide EI (NEI) (reviewed 2026-11-06) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Neuropeptide EI (NEI) products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a drug: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no substance record for neuropeptide EI (searched November 6, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Neuropeptide EI is a research peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
Neuropeptide EI has no approved use and no label. These points reflect its research status.
Legal Status
Neuropeptide EI is an endogenous prepro-MCH-derived peptide studied as a research compound; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is neuropeptide EI?
A short amidated brain peptide (named for its glutamic acid (E) and isoleucine (I)) cut from the same precursor as melanin-concentrating hormone (MCH); the two are made in and released from the same hypothalamic neurons.
?What does it do?
It stimulates luteinizing-hormone (LH) release by acting on GnRH neurons and the pituitary (PMIDs 15501532, 17016031), and it shapes behaviour — inducing grooming and locomotion via dopamine and beta-1 adrenergic systems (PMID 17537427) and anxiety-like behaviour from the amygdala (PMID 21164371).
?How is it related to MCH?
Both NEI and MCH are cut from the same prepro-MCH precursor and are co-stored and co-released. The longer combined fragment 'NEI-MCH' is a protease-resistant feeding superagonist at MCH receptors. Grey Peptides has a separate entry for melanin-concentrating hormone.
?Is it approved or available to buy?
No. Neuropeptide EI is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online as neuropeptide EI is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [review] Bittencourt J, et al. "Anatomy, function and regulation of neuropeptide EI (NEI)." Peptides, 2008;29(8):1441-50. PMID: 18456371.
- [animal] Attademo AM, et al. "Intracerebroventricular injection of neuropeptide EI increases serum LH in male and female rats." Peptides, 2004;25(11):1995-9. PMID: 15501532.
- [animal] Attademo AM, et al. "Neuropeptide glutamic acid-isoleucine may induce luteinizing hormone secretion via multiple pathways." Neuroendocrinology, 2006;83(5-6):313-24. PMID: 17016031.
- [animal] Gastón S, et al. "Intra-amygdaloid microinjection of neuropeptide glutamic acid-isoleucine induces anxiety-like behavior." Neuroreport, 2011;22(2):83-7. PMID: 21164371.
- [mechanism] Sánchez-Borzone ME, et al. "Effect of beta-adrenoceptors on the behaviour induced by the neuropeptide glutamic acid isoleucine amide." Eur J Pharmacol, 2007;568(1-3):186-91. PMID: 17537427.
- [mechanism] Parkes D, et al. "Secretion of melanin-concentrating hormone and neuropeptide-EI from cultured rat hypothalamic cells." Endocrinology, 1992;131(4):1826-31. PMID: 1327720.
- [other] UniProt P20382 (pro-MCH, PMCH gene), read November 6, 2026: neuropeptide EI (NEI) is a short amidated peptide processed from prepro-melanin-concentrating hormone, the same precursor that yields melanin-concentrating hormone (MCH); NEI is named for its N-terminal glutamic acid (E) and isoleucine (I). https://www.uniprot.org/uniprotkb/P20382/entry
- [other] Neuropeptide EI (NEI) was predicted from the MCH precursor and first demonstrated as a secreted peptide from hypothalamic cells; its processing from prepro-MCH, its co-localisation with MCH, and its roles in LH release and behaviour are from the studies carded on this page (read November 6, 2026).
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 6, 2026: no application and no label record for neuropeptide EI. It is an endogenous neuropeptide, not a registered drug; FDA GSRS and ChEMBL hold no substance record for it.
Sources & Citations
The six studies carded above were read from their PubMed records on November 6, 2026. Identity comes from UniProt (P20382, pro-MCH): NEI is a short amidated peptide processed from prepro-MCH, co-made with MCH. Its co-localisation with MCH, its stimulation of LH release via GnRH neurons and the pituitary, its grooming, locomotor and anxiety-like behavioural effects and the adrenergic systems behind them, and its first demonstration as a secreted peptide are from the studies carded on this page; the absence of US approval and of a drug substance record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.