A tripeptide (Pro-Leu-Gly-NH2) that is also the C-terminal tail of oxytocin. Originally identified as an amphibian MSH-release inhibitor; modern interest is as a positive allosteric modulator of D2 dopamine receptors. Small 1970s/80s human trials in Parkinson's and depression; never approved as a drug.
MIF-1 (Melanocyte-stimulating hormone release-Inhibiting Factor 1) is the tripeptide Pro-Leu-Gly-NH2 — three amino acids with a C-terminal amide. Also called Melanostatin or simply PLG.
Identity quirk: it's the oxytocin tail. Oxytocin's sequence is Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2; the C-terminal tripeptide is Pro-Leu-Gly-NH2 — that's MIF-1. It can be enzymatically cleaved from oxytocin in vivo, which is part of how the molecule was originally identified.
Discovered in 1971: Nair, Kastin, Schally Biochem Biophys Res Commun 1971 (PMID 4398196, foundational identity paper) and Celis, Taleisnik, Walter PNAS 1971 (PMID 5283931, independent structure confirmation). Originally proposed as a hypothalamic factor inhibiting MSH release in amphibian models. The "human MSH-release inhibitor" framing is dated — modern interest is in central D2 receptor modulation.
Naming note: "Melanostatin DM" appears occasionally on vendor pages. The "DM" suffix appears in zero peer-reviewed primary-literature records — it's a vendor SKU code, not a chemical designator. Use "MIF-1," "Melanostatin," "Pro-Leu-Gly-NH2," or "PLG" instead.
The most rigorously characterized modern action of MIF-1 is as a positive allosteric modulator (PAM) of dopamine D2 receptors. MIF-1 doesn't directly activate D2 itself — it binds an allosteric site that amplifies D2 activation by endogenous dopamine or by D2 agonists. Costa-Almeida et al. 2026 (PMID 41687543) characterized MIF-1 as a first-in-class ago-allosteric D2 PAM. The allosteric mechanism is consistent with dose-response data showing biphasic effects (moderate doses better than high doses) — classic PAM behavior. This makes MIF-1 a candidate L-DOPA potentiator in Parkinson's disease, since L-DOPA-derived dopamine acts on D2 and PAMs amplify that signal.
Originally identified in amphibian skin-darkening assays as a factor that inhibited MSH release. The amphibian biology was real but the human relevance has been controversial since the 1970s. The "MSH-inhibitor" framing shouldn't be the lead in modern human-use copy.
What MIF-1 isn't: not a direct D2 agonist (allosteric only); not a melanocortin agonist or antagonist (despite the original "MSH-inhibitor" naming); not an opioid agonist (see the opioid section below for an important encyclopedia correction).
The MIF-1 human-trial era was the late 1970s and 1980s, in two main indications: Parkinson's disease and depression. Outcomes were mixed and small. No modern Phase 2/3 trial exists.
Parkinson's disease. Several small open-label PD pilots in the 1970s reported some symptomatic improvement. The existing StackTrax encyclopedia cites those positive 1970s pilots while omitting Caraceni & Parati 1979 (PMID 39308) — "Failure of MIF-I to affect behavioral responses in patients with Parkinson's disease under L-dopa therapy" — the explicit negative trial. Net read: signal possibly real, possibly placebo, definitely not robustly replicated. Modern PD therapeutics didn't build on MIF-1.
Depression. Ehrensing & Kastin 1978 (PMID 25588) was a small placebo-controlled trial in depressed patients showing antidepressant signal at moderate doses with biphasic dose-response — moderate doses worked better than high doses. The pattern is consistent with the modern D2-PAM mechanism. Implication: a "more is better" dosing framing is mechanistically wrong for MIF-1. No modern depression trial has been conducted.
Opioid interaction — encyclopedia correction. The existing StackTrax encyclopedia entry claims MIF-1 "reduces opioid tolerance / attenuates withdrawal." That's wrong — the effect refers to a different molecule, cyclo(Leu-Gly). The actual MIF-1 (Pro-Leu-Gly-NH2) literature shows the opposite direction: MIF-1 antagonizes morphine analgesia in animal and human studies (PMID 6151672, including in humans). Cyclo(Leu-Gly) is a cyclic-dipeptide derivative with different pharmacology — that's the work that produced the "reduces opioid tolerance" findings. The encyclopedia conflated parent MIF-1 with cyclo(Leu-Gly); this guide corrects that.
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Start Tracking FreePro-Leu-Gly-NH2 is a tripeptide (~285 Da), unprotected by terminal modifications other than the C-terminal amide. Plasma half-life on the order of minutes in animal models. Routes used in published studies span oral, IV, intranasal, and IM (all reported in 1970s/80s human trials). BBB penetration is reported in older literature based on CNS pharmacodynamic effects in animals; quantitative human CSF or PET data not located. Bioavailability is not well-characterized but generally consistent with what would be expected for a small unmodified peptide.
The biphasic dose-response in depression (PMID 25588) means a higher dose isn't necessarily a stronger dose — PAM behavior at the receptor level can produce inverted-U curves where over-dosing reduces effect.
StackTrax doesn't endorse MIF-1 use. No modern controlled trial. The dosing below reflects historical 1970s/80s trial doses plus community convention.
| Parameter | Range |
|---|---|
| Dose (intranasal, community) | 50–200 µg/day, often split AM/PM |
| Dose (SC, less common) | 50–200 µg/day |
| Cycle length | 2–6 weeks (community); historical depression trials were 4–6 weeks |
| Route | Intranasal most common; SC less common; oral poorly characterized |
Moderate doses outperformed high doses in the only positive depression trial. "More is better" is mechanistically wrong for MIF-1.
Pre-filled with a typical MIF-1 (Melanostatin) setup. Edit any field — the draw updates live.
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From the 1970s/80s human trials and limited modern community reports: generally well tolerated in the small published trials; occasional headache; mild GI effects with oral dosing; nasal irritation with intranasal route; no distinctive serious adverse-event pattern.
Theoretical concerns (none validated in long-term human use): D2 PAM activity could theoretically exacerbate psychotic symptoms in vulnerable individuals; MIF-1 may reduce opioid analgesic effect (PMID 6151672); no published carcinogenicity, reproductive toxicity, or chronic-use safety data; no Western pharmacovigilance database data.
| Compound | Mechanism / nature | Difference from MIF-1 |
|---|---|---|
| Oxytocin | Full 9-aa neuropeptide | MIF-1 is the C-terminal tripeptide. Different mechanism (OXTR vs D2 PAM). |
| Cyclo(Leu-Gly) | Cyclic dipeptide derivative | Different molecule. The "reduces opioid tolerance" claim refers to this, not MIF-1. MIF-1 itself antagonizes opioid analgesia (PMID 6151672). |
| TRH | Tripeptide pGlu-His-Pro-NH2 | Different sequence and target (TSH/PRL vs D2). |
| α-MSH and melanocortin agonists (PT-141, MT-1, MT-2) | Melanocortin receptor agonists | Despite the original "MSH-inhibitor" naming, MIF-1 doesn't act on melanocortin receptors at relevant concentrations. |
| Semax | ACTH(4–7) analog with PGP cap | Different target (BDNF/NGF). Both small synthetic peptides with central effects, mechanistically distinct. |
| Selank | Tuftsin analog | GABAergic anxiolytic mechanism. |
| L-DOPA / levodopa | Dopamine precursor (FDA-approved PD drug) | L-DOPA increases dopamine; MIF-1 amplifies response via D2 PAM. Complementary but not equivalent. |
| D2 agonists (pramipexole, ropinirole) | Direct D2 agonists | MIF-1 is allosteric only; doesn't directly activate D2. |
MIF-1 (Melanostatin) is a research peptide not approved by the FDA for human use. It is sold only as a research chemical, and StackTrax does not endorse or facilitate personal use.
Quality varies enormously among research-chemical suppliers. At minimum, look for:
StackTrax’s preferred partner NextGen Peptides does not currently carry MIF-1 (Melanostatin)in their catalog, which is why you don’t see a direct purchase link here. Other major research-chemical suppliers carry it; we don’t specifically recommend one for this compound.
Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
Start Tracking FreeMIF-1 (Melanocyte-stimulating hormone release-Inhibiting Factor 1) is the tripeptide Pro-Leu-Gly-NH2 — three amino acids with a C-terminal amide. Also called Melanostatin or PLG. It is identity-quirk equal to the C-terminal tail of oxytocin (whose full sequence is Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2), and it can be enzymatically cleaved from oxytocin in vivo. Originally identified in 1971 by Nair, Kastin, and Schally (PMID 4398196) as a hypothalamic factor inhibiting MSH release in amphibian models.
Modestly characterized at best. The MIF-1 human-trial era was the late 1970s and 1980s, with two main indications: Parkinsons disease and depression. Several small open-label Parkinsons pilots in the 1970s reported some symptomatic improvement, but Caraceni and Parati 1979 (PMID 39308) is an explicit negative trial — "Failure of MIF-I to affect behavioral responses in patients with Parkinsons disease under L-dopa therapy." Ehrensing and Kastin 1978 (PMID 25588) was a small placebo-controlled depression trial showing antidepressant signal at moderate doses with biphasic dose-response. No modern Phase 2/3 trial exists.
The most rigorously characterized modern action of MIF-1 is as a positive allosteric modulator (PAM) of dopamine D2 receptors. MIF-1 does not directly activate D2 — it binds an allosteric site that amplifies D2 activation by endogenous dopamine or by D2 agonists. Costa-Almeida et al. 2026 (PMID 41687543) characterized MIF-1 as a first-in-class ago-allosteric D2 PAM. The allosteric mechanism is consistent with the biphasic dose-response in the depression literature (moderate doses outperform high doses) — classic PAM behavior. The original "MSH-inhibitor" framing reflects amphibian biology that does not translate cleanly to humans.
No. MIF-1 has never been FDA-approved or EMA-approved. No NDA, no IND on file. Sold as a research chemical only. WADA 2026 prohibited list does not name MIF-1 specifically, but the S0 catch-all (non-approved substances) may apply to athletes subject to anti-doping testing.
No — that is a common encyclopedia error that conflates MIF-1 with a different molecule, cyclo(Leu-Gly). The actual MIF-1 (Pro-Leu-Gly-NH2) literature shows the OPPOSITE direction: MIF-1 antagonizes morphine analgesia in animal and human studies (PMID 6151672). Cyclo(Leu-Gly) is a cyclic-dipeptide derivative with different pharmacology, and that is the work that produced the "reduces opioid tolerance" findings. If you are on opioid analgesics, MIF-1 may reduce their analgesic effect.
No modern controlled trial. Community-practice dosing is 50–200 mcg per day intranasally (often split AM/PM), or 50–200 mcg per day subcutaneously, for 2–6 weeks (historical depression trials were 4–6 weeks). Crucially: moderate doses outperformed high doses in the only positive depression trial. "More is better" is mechanistically wrong for MIF-1 — PAM behavior at the receptor level can produce inverted-U dose-response curves where over-dosing reduces effect.
In the 1970s and 1980s human trials, MIF-1 was generally well tolerated in the small published cohorts, with occasional headache, mild GI effects with oral dosing, and nasal irritation with intranasal route. Theoretical concerns (none validated long-term): D2 PAM activity could exacerbate psychotic symptoms in vulnerable individuals; MIF-1 may reduce opioid analgesic effect; no published carcinogenicity, reproductive toxicity, or chronic-use safety data; no Western pharmacovigilance database entries.
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