Neurokinin B
The hypothalamic peptide that puberty depends on and that sets off menopausal hot flushes, studied in families, brains and infusion trials
Neurokinin B is a short peptide made in the hypothalamus by the same neurons that make kisspeptin and dynorphin. People born without a working copy of its gene, TAC3, or its receptor do not enter puberty unaided. After menopause these neurons enlarge, and when researchers infused neurokinin B into healthy women most of them flushed within minutes. That finding is why drugs that block its receptor now treat hot flushes. Neurokinin B itself has been given to people only in short research infusions.
Used in human trials: 0.4 to 5.12 nmol/kg/h, Continuous infusion, Intravenous (Study: healthy men and women, reproductive hormones (range tested)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Neurokinin B belongs to the tachykinins, the family that also includes substance P and neurokinin A. Its 10 residues end in the Phe-X-Gly-Leu-Met-amide motif the family shares, and it acts mainly on the neurokinin 3 receptor. In the human brain it is made in the infundibular (arcuate) nucleus by neurons that also carry kisspeptin and dynorphin, a group researchers call KNDy neurons.
Its importance to people was settled by genetics. In 2009 four families were described in which everyone affected carried two broken copies of TAC3 or of its receptor gene; none went through puberty and all lacked the pituitary hormones that drive the testes and ovaries. A larger screen of 345 patients with the same condition found receptor variants in 19 and a single TAC3 deletion that removed the peptide entirely. Fifteen of 16 affected males had a micropenis, yet several patients later recovered hormone production after treatment stopped, suggesting the pathway matters most early in life. In patients with these mutations, a continuous kisspeptin infusion restored pulsed hormone release, which places neurokinin B upstream of kisspeptin.
Giving neurokinin B to adults has been less dramatic than losing it. In the first infusion study, healthy men and women received rates up to 5.12 nmol/kg/h, in sessions lasting up to eight hours, without any change in LH, FSH, testosterone or estradiol. In men, adding it to a kisspeptin-54 infusion actually blunted kisspeptin's rise in gonadotropins. Its clearest effect in people is on temperature: a 30-minute infusion caused flushing in 8 of 10 healthy women, with a faster heart rate and warmer skin, and none flushed on placebo.
That result matches the brain tissue. Post-mortem studies found more neurokinin B staining in the infundibular nucleus of women than of men, and more again after menopause, when estrogen falls. Reviews describe how these neurons project to the brain's heat-loss centres and how blocking the neurokinin 3 receptor stops flushes within days; one such blocker, fezolinetant, is now approved for menopausal hot flushes. That drug is not neurokinin B and is not covered here.
Outside the brain, neurokinin B is made by the placenta. One group found it in the outer cell layer of the placenta, measurable in maternal plasma from week 9, and grossly raised in pre-eclampsia; two South African studies confirmed higher third-trimester levels in pre-eclampsia, about 15 to 24 ng/L against about 4 ng/L in healthy pregnancy. Whether it causes the disease is unproven: on vessels from pregnant women it relaxed arteries rather than constricting them.
Mechanism of Action
Neurokinin B is released by KNDy neurons in the hypothalamus and acts on neurokinin 3 receptors, both on neighbouring neurons that control GnRH release and on pathways to the brain's temperature centres.
Puberty switch
Loss of TAC3 or its receptor leaves GnRH pulses too weak to start puberty; kisspeptin can stand in, so neurokinin B works upstream of it.
Hot flushes
After menopause its neurons enlarge; infused into women it caused flushes, and blocking its receptor relieves them.
Placenta
The placenta makes it from early pregnancy, and plasma levels are higher in pre-eclampsia.
Published Research
These are studies of neurokinin B itself, read from their PubMed abstracts: genetic studies of its gene, research infusions in healthy volunteers, measurements in human brain, placenta and blood, one monkey study, and three reviews. Trials of drugs that block its receptor are not carded here.
An infusion brings on hot flushes
In a randomised, double-blind, placebo-controlled crossover study, ten healthy women each received a 30-minute intravenous infusion of neurokinin B and one of vehicle. Eight flushed during neurokinin B and none during vehicle; flushes came with a higher heart rate and a rise in skin temperature measured by probe and by thermal camera.
No change in reproductive hormones
The first clinical study of neurokinin B gave it intravenously to 23 healthy men and 11 healthy women at 0.4 to 5.12 nmol/kg/h, for 90 minutes up to 8 hours and at three phases of the menstrual cycle. No dose changed LH, FSH, testosterone or estradiol, or the pulsing of LH, compared with vehicle.
Given with kisspeptin, it damped the response
Healthy men (five per group) received 8-hour infusions of neurokinin B at 2.56 nmol/kg/h, kisspeptin-54, oral naltrexone, or combinations. Neurokinin B alone did not change gonadotropins, and adding it to kisspeptin gave a significantly smaller rise in LH and FSH than kisspeptin alone.
Broken gene, no puberty
Four families with severe congenital gonadotropin deficiency and failed puberty were described; every affected member carried two loss-of-function copies of TAC3, which encodes neurokinin B, or of TACR3, its receptor. The finding marked neurokinin B as a central regulator of human reproduction.
Mutations common, and often reversible
Sequencing of 345 patients with normosmic hypogonadotropic hypogonadism found 13 distinct TACR3 variants in 19 probands and one homozygous TAC3 deletion that removed the peptide. Fifteen of 16 affected males had a micropenis; after treatment was stopped, six of seven males and four of five females tested showed signs of recovery.
Kisspeptin bypasses the missing signal
In patients with loss-of-function mutations in TAC3 or its receptor gene, a continuous kisspeptin infusion restored pulsatile LH secretion. The authors concluded that neurokinin B acts upstream of kisspeptin in the chain that drives GnRH release.
More in women, more after menopause
Immunostaining of post-mortem hypothalamus showed a female-dominant sex difference in neurokinin B in the infundibular nucleus that emerged around puberty and persisted into old age. Postmenopausal women had significantly more neurokinin B staining than premenopausal women, and male-to-female transgender people had a female-typical pattern.
Made by the placenta, high in pre-eclampsia
A placental complementary DNA coded for a mature peptide identical to neurokinin B, expressed in the outer syncytiotrophoblast. It was measurable in maternal plasma from week 9 and grossly elevated in pregnancy-induced hypertension and pre-eclampsia; in rats, levels several times above late pregnancy raised blood pressure.
Higher plasma levels confirmed
In 43 women with pre-eclampsia and 62 healthy pregnant women in Cape Town, mean plasma neurokinin B was 23.5 ng/L against 3.8 ng/L. Two immunoassay methods agreed closely (r = 0.904); the authors left open whether the rise causes the disease.
Same rise in a second population
Third-trimester plasma neurokinin B was measured in 72 women with pre-eclampsia and 94 healthy pregnant women of mixed and Black African ancestry. Means were 23.5 and 15.0 ng/L in the two pre-eclampsia groups against 3.8 and 4.4 ng/L in controls.
It relaxes pregnancy vessels
Arteries and veins dissected from biopsies taken at caesarean section (26 women) relaxed in a dose-dependent way when exposed to neurokinin B, and endothelium-dependent relaxation was unchanged. The authors concluded it is not the circulating factor that raises vascular resistance in pre-eclampsia.
Brief bursts of GnRH in monkeys
In castrated juvenile male rhesus monkeys, a single intravenous injection of neurokinin B set off a burst of LH that a GnRH-receptor blocker abolished, showing a hypothalamic action. Neurokinin B and kisspeptin were found in the same arcuate cell bodies and fibres.
The KNDy hypothesis of hot flushes
This review proposed that KNDy neurons relay estrogen signals to preoptic temperature centres. In rats they project to areas carrying the neurokinin 3 receptor, activating that receptor lowers body temperature, and removing the neurons reduces skin vasodilation.
Blocking the pathway for hot flushes
A review of neurokinin B antagonists for menopausal hot flushes, noting their very fast onset within one or two days and large effects on daytime flushes and night-time sleep disturbance, while calling for long-term safety data.
Kisspeptin and neurokinin B in reproductive health
A review of both peptides across puberty, the menstrual cycle, pregnancy, menopause and bone. It notes that neurokinin B's role in hot flashes led to fezolinetant, a neurokinin 3 receptor antagonist now approved by the FDA for menopausal vasomotor symptoms.
Dosing Data
Neurokinin B is not approved anywhere as a medicine. These are research infusion rates from published human studies, as stated in their abstracts; none was a treatment course.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or 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 Neurokinin B is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: intravenous). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Neurokinin B, 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 Neurokinin B stays intact once mixed.
How it is taken
As it was given in human studies: Intravenous (Continuous infusion; Study: healthy men and women, reproductive hormones (range tested)).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: healthy men and women, reproductive hormones (range tested): 90 minutes to 8 hours; Study: healthy men, combined with kisspeptin-54 or naltrexone: 8 hours.
When effects appear: unknown; no source on this page gives a time to effect for Neurokinin B. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Flushing, with a faster heart rate and warmer skin, in 8 of 10 healthy women during a 30-minute infusion (PMID 25683060); No safety data beyond single infusions lasting minutes to hours. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Neurokinin B. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the short infusion studies above, which reported little on safety”).
Interactions
- kisspeptin-54 (co-infused in healthy men): co-infused neurokinin B gave a significantly smaller rise in LH and FSH than kisspeptin alone; neurokinin B alone did not change gonadotropins
Every peptide's record, with its source: the interaction matrix.
Source: human study, PMID 27379743.
Checking what you bought
Unknown: no published independent test of Neurokinin B 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; it checks the measured mass against Neurokinin B's expected mass, 1,210.4 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine anywhere in the sources read). Sport: Prohibited (S0 catch-all).
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
From the short infusion studies above, which reported little on safety.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Neurokinin B is a research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is neurokinin B?
A 10-amino-acid tachykinin peptide made in the hypothalamus, mostly by the same neurons that make kisspeptin. It acts on the neurokinin 3 receptor.
?Does neurokinin B cause hot flushes?
It can. A 30-minute infusion caused flushing in 8 of 10 healthy women, none on placebo, and the brain makes more of it after menopause.
?Is fezolinetant the same thing?
No. Fezolinetant blocks the neurokinin 3 receptor, the opposite of what neurokinin B does; it is a separate drug approved for menopausal hot flushes.
?What happens without neurokinin B?
People with two broken copies of its gene or its receptor gene do not go through puberty without treatment, though some later recover hormone production.
?Does an infusion raise testosterone or estrogen?
No. In healthy men and women, infusions up to 5.12 nmol/kg/h for up to 8 hours did not change LH, FSH, testosterone or estradiol.
?Is it linked to pre-eclampsia?
Plasma levels are several times higher in pre-eclampsia, but whether it causes the disease is unproven; it relaxed rather than tightened vessels from pregnant women.
References
- [clinical-trial] Jayasena CN, et al. "Neurokinin B administration induces hot flushes in women." Sci Rep, 2015;5:8466. PMID: 25683060.
- [clinical-trial] Jayasena CN, et al. "Effects of neurokinin B administration on reproductive hormone secretion in healthy men and women." J Clin Endocrinol Metab, 2014;99(1):E19-27. PMID: 24170109.
- [clinical-trial] Narayanaswamy S, et al. "Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men." J Clin Endocrinol Metab, 2016;101(9):3429-36. PMID: 27379743.
- [pubmed] Topaloglu AK, et al. "TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction." Nat Genet, 2009;41(3):354-358. PMID: 19079066.
- [pubmed] Gianetti E, et al. "TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood." J Clin Endocrinol Metab, 2010;95(6):2857-67. PMID: 20332248.
- [clinical-trial] Young J, et al. "Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies: physiological, pathophysiological and therapeutic implications." Neuroendocrinology, 2013;97(2):193-202. PMID: 22377698.
- [pubmed] Taziaux M, et al. "Sex differences in the neurokinin B system in the human infundibular nucleus." J Clin Endocrinol Metab, 2012;97(12):E2210-20. PMID: 23019350.
- [pubmed] Page NM, et al. "Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia." Nature, 2000;405(6788):797-800. PMID: 10866201.
- [pubmed] Geissbuehler V, et al. "Altered plasma neurokinin B levels in patients with pre-eclampsia." Arch Gynecol Obstet, 2007;276(2):151-7. PMID: 17318561.
- [pubmed] Geissbuehler V, et al. "Third trimester plasma neurokinin B levels in women with and without preeclampsia." J Matern Fetal Neonatal Med, 2008;21(2):95-100. PMID: 18240076.
- [pubmed] Wareing M, et al. "Vasoactive effects of neurokinin B on human blood vessels." Am J Obstet Gynecol, 2003;188(1):196-202. PMID: 12548217.
- [pubmed] Ramaswamy S, et al. "Neurokinin B stimulates GnRH release in the male monkey (Macaca mulatta) and is colocalized with kisspeptin in the arcuate nucleus." Endocrinology, 2010;151(9):4494-503. PMID: 20573725.
- [review] Rance NE, et al. "Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes." Front Neuroendocrinol, 2013;34(3):211-27. PMID: 23872331.
- [review] Anderson RA, et al. "The neurokinin B pathway in the treatment of menopausal hot flushes." Climacteric, 2019;22(1):51-54. PMID: 30572747.
- [review] Koysombat K, et al. "Kisspeptin and neurokinin B: roles in reproductive health." Physiol Rev, 2025;105(2):707-764. PMID: 39813600.
- [other] UniProt Q9UHF0 (TKNK_HUMAN), tachykinin-3 precursor; peptide 81-90 is neurokinin B (DMHDFFVGLM), C-terminal methionine amide. Read October 30, 2026. https://www.uniprot.org/uniprotkb/Q9UHF0/entry
Sources & Citations
Every study on this page was read from its PubMed record on October 30, 2026. Regulatory status comes from Drugs@FDA (openFDA) and the EMA medicines list, read 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.