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Nemifitide (originally coded INN 00835, and briefly called netamiftide) is a synthetic pentapeptide that was developed as an injectable antidepressant. Its sequence is 4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginyl-glycyl-L-tryptophanamide, and it is a structural analog of MIF-1 (melanocyte-inhibiting factor-1, the tripeptide Pro-Leu-Gly-NH2). It was studied by Innapharma, later Tetragenex Pharmaceuticals, and reached Phase II trials in major depressive disorder before development stalled; it was never approved. The interesting thing about it is the mismatch between its pharmacokinetics and its effect: the peptide clears the blood in well under an hour, yet the antidepressant response reported in trials came on within days and lasted weeks to months after a short dosing course. It was given as a subcutaneous injection, not a pill, and its tolerability was consistently good with side effects limited mostly to the injection site.
- Mood response reported within about 48 hours
- Effects that held for weeks after a short course
- Clean tolerability; side effects mostly at the injection site
- Beat placebo in a phase 2 depression study
- Signal even in stubborn, treatment resistant cases
- Injection-site pain and redness, more common at high doses (240 to 320 mg)
- Its plasma half-life is only about 15 to 30 minutes, yet trial patients reportedly stayed better for weeks to months after a short course; the effect clearly outlives the drug.
- It is a chemical relative of MIF-1, a natural brain peptide studied for mood since the 1970s, rather than a monoamine drug like an SSRI.
- It was given by subcutaneous injection, and one study even tested a needle-free jet injector, which delivered similar drug exposure to a standard needle.
- In a rat model of depression it showed a strange biphasic dose-response, working at low and high doses but not the doses in between.
- It briefly carried the name 'netamiftide' before 'nemifitide' was finalized as its international nonproprietary name.
Mechanism
The precise molecular target of nemifitide is not established; this is an honest gap in the literature, not something the site is glossing over. The design rationale is that it is an analog of MIF-1 (Pro-Leu-Gly-NH2), an endogenous that modulates dopaminergic and opioid neurotransmission and has itself been explored for antidepressant activity. Nemifitide is not a classical monoamine . The most direct pharmacodynamic signal in humans came from platelet studies: treatment increased the rate of platelet () uptake, and this change tracked with clinical response, which points to some downstream effect on serotonergic signaling rather than acute reuptake blockade.
In a genetic rat model of depression (the Flinders Sensitive Line), it reduced immobility in the forced swim test with an unusual biphasic dose-response, working at low and high doses but not at intermediate ones. There is no receptor binding or affinity data for nemifitide in ChEMBL, so any single-receptor mechanism story would be speculation. What the evidence supports is a neuromodulatory whose antidepressant effect appears to be triggered rather than sustained by continuous drug presence.
receptor fingerprint
MIF-1 / melanocyte-inhibiting-factor system (Pro-Leu-Gly-NH2 analog)Neuromodulator (structural analog)
receptor (putative, by analogy to MIF-1)Possible allosteric modulator (unconfirmed for nemifitide)
Platelet / central () uptakeIndirect modulator
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Across Phase I and Phase II studies the tolerability profile was one of nemifitide's strong points. In more than 100 healthy volunteers dosed in Phase I, no serious or clinically significant systemic adverse events occurred; the drug-related effects were local and transient, mostly injection-site pain and redness, and these were more common at the highest doses (240 to 320 mg).
In the controlled efficacy trials the incidence of side effects was comparable to placebo, there were no dropouts due to adverse events in the 30/45 mg study, and no clinically significant systemic effects were seen on re-treatment. That said, this is an investigational compound that was only ever given as a subcutaneous injection under trial supervision; it is not approved, not marketed, and never completed the larger Phase III testing that would characterize rarer or longer-term risks. It should be treated as unproven, not as a validated therapy.
Reconstitutionarithmetic only, not dosing advice
arithmetic only; not medical or dosing advice.
History
Nemifitide grew out of decades of work on MIF-1, a small brain peptide that researchers including Abba Kastin and Rudolph Ehrensing had linked to mood as far back as the 1970s. Innapharma synthesized INN 00835 as a more potent, metabolically modified MIF-1 analog and pushed it into clinical development for major depression around the turn of the 2000s, briefly under the name netamiftide before nemifitide became the settled INN (the USAN -tide peptide stem was assigned in 2002). Placebo-controlled Phase II work through the early 2000s reported rapid onset and durable response, and by the mid-2000s a Phase III program was anticipated. The asset later moved to Tetragenex Pharmaceuticals. It never reached the market, and it is now mainly cited in reviews as one of the neuropeptide-based approaches to depression that showed early promise but did not cross the finish line.
Reputation
In the research literature nemifitide is remembered as an intriguing near-miss: a peptide antidepressant with a genuinely unusual profile (fast onset, long-lasting effect from brief dosing, clean tolerability) that repeatedly showed up in antidepressant-pipeline and 'emerging targets' reviews of the late 2000s. It never built a following outside clinical development because it was an injectable investigational drug, not something available to consumers, and it quietly disappeared from the pipeline without a Phase III readout. Among people who follow experimental antidepressants it is a curiosity rather than a staple, and there is no meaningful community-use or nootropic-stack track record for it.
Subjective profileweighing the evidence above
The interesting part is that the antidepressant effect outlasted the drug by weeks, and tolerability was excellent, with injection-site pain the main complaint. It still stalled before Phase III, so it is unavailable and unproven, and its mechanism was never pinned down.
Where to buy
Suppliers
Vendors carrying Nemifitide, with live product details and codes. Links are affiliate links that support the wiki at no cost to you.
RUO
Nemifitide
Research
- 1999first citedThe effect of treatment with a new antidepressant, INN 00835, on platelet serotonin uptake in d…
- 2006controlled trialEfficacy and safety of 30 mg/d and 45 mg/d nemifitide compared to placebo in major depressive d…
- 2009most recentEmerging targets for antidepressant therapies.
- 1.Efficacy and safety of 30 mg/d and 45 mg/d nemifitide compared to placebo in major depressive disorder.
- 2.Clinical effect of nemifitide, a novel pentapeptide antidepressant, in the treatment of severely depressed refractory patients.
- 3.Clinical effectiveness of nemifitide, a novel pentapeptide antidepressant, in depressed outpatients: comparison of follow-up re-treatment with initial treatment.
- 4.Antidepressant-like effects of a novel pentapeptide, nemifitide, in an animal model of depression.
- 5.Clinical pharmacokinetic studies with INN 00835 (nemifitide), a novel pentapeptide antidepressant.
- 6.Double-blind, placebo-controlled study of INN 00835 (netamiftide) in the treatment of outpatients with major depression.
- 7.A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression.
- 8.The effect of treatment with a new antidepressant, INN 00835, on platelet serotonin uptake in depressed patients.
- 9.Comparison of systemic exposure to nemifitide following two methods of subcutaneous administration to healthy volunteers.
- 10.Nemifitide. Innapharma.
- 11.Novel targets for antidepressant therapies.
- 12.Emerging targets for antidepressant therapies.
12 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is nemifitide approved or available anywhere?
No. It reached Phase II clinical trials for major depression under Innapharma and later Tetragenex Pharmaceuticals, but it was never approved and never completed Phase III. Everything known about it comes from trial and preclinical data, and it is not sold as a medicine or supplement.
How does it work?
Honestly, that is not fully known. It is a synthetic analog of MIF-1, a natural brain peptide tied to dopamine and mood, and in patients it changed platelet serotonin uptake in a way that tracked with improvement. But there is no receptor binding or affinity data for it in ChEMBL, so a precise single-target mechanism has not been established. It is not a conventional SSRI or reuptake inhibitor.
Why is it injected instead of taken as a pill?
It is a peptide, and peptides are generally broken down in the gut, so it was developed for subcutaneous injection. Trials delivered it by standard needle and even tested a needle-free jet injector, which gave similar drug levels.
How can the effect last months if the drug clears in under an hour?
That is the most unusual thing about it. Its plasma half-life is only about 15 to 30 minutes, yet reported antidepressant benefit came on within days and persisted for weeks to months after a brief course. This suggests it triggers a lasting neurobiological change rather than needing continuous presence in the blood, though the exact reason was never nailed down.
Was it actually effective in depression?
The Phase II evidence was promising but limited. A placebo-controlled study found the 45 mg/day dose separated from placebo, and open-label work suggested benefit even in treatment-resistant patients. These were relatively small trials with notable placebo responses, and the compound never got the large Phase III confirmation that would settle the question.
Limitations of the evidence
- Unknown long-term safety; never completed Phase III
- Mechanism and any receptor-level risks are poorly characterized
- Not approved or available; anything beyond trial data is unverified
Adverse effects
- Injection-site pain and redness, more common at high doses (240 to 320 mg)
Notes and cautions
- Requires subcutaneous injection rather than oral dosing
- No published study has administered nemifitide by the intranasal route. Every human trial found in PubMed, searched under nemifitide, netamiftide and the code INN 00835, delivered the pentapeptide by subcutaneous injection, including the placebo controlled depression studies that reported its rapid onset. Crossing those names with intranasal and nasal terms returns nothing. Nasal absorption, dose and tolerability are all unknown for this compound.