What it is
Semax is a lab-made chain of seven amino acids. Four of them copy positions 4 to 7 of ACTH, a pituitary hormone that normally signals the adrenal glands to release cortisol. The other three (proline, glycine, proline) were added so the chain would survive longer in the body. Its developers report that it does not stimulate the adrenal glands, and it has been studied for effects on the brain rather than on hormones.
In Russia, Semax is a registered medicine in the form of nose drops in two strengths. It is not approved in the United States. Most of what is known about it comes from Russian laboratories and Russian-language clinical reports, many of them small.
Semax is H-Met-Glu-His-Phe-Pro-Gly-Pro-OH (C37H51N9O10S, 813.9 g/mol, CAS 80714-61-0): ACTH(4-7) extended at the C-terminus with the glyproline Pro-Gly-Pro to slow proteolysis. The developing institute reports that it has neither corticotropic nor melanocyte-stimulating activity (Kolomin et al. 2013).
No specific receptor has been identified. Dolotov et al. (2006) reported saturable binding sites in rat basal forebrain and higher BDNF protein after exposure; other rodent studies report rapid changes in Bdnf, Ngf and TrkB expression, and in immune- and vascular-related transcripts after experimental focal ischaemia (Medvedeva et al. 2014). Further rodent findings include anticoagulant and antiplatelet effects, partly attributed to the Pro-Gly-Pro metabolite, and potentiation of amphetamine-induced striatal dopamine release.
Pharmacokinetics are known only from rats. Labelled Semax is hydrolysed quickly by aminopeptidases and angiotensin-converting enzyme, mainly to Pro-Gly-Pro. In the rat studies summarised by FDA, about 0.07% of the dose reached the brain after intranasal dosing, against about 0.005% after intravenous dosing. FDA found no human pharmacokinetic study by any route.
Who made it and when
A team led by Nikolai Myasoedov and Igor Ashmarin began the work in the late 1970s at what is now the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow. Natural ACTH fragments act for only 30 to 60 minutes, and the aim was a version whose effects lasted longer. The result was developed into 0.1% nose drops and, by 2001, a stronger 1% version aimed at patients after a stroke. Both appear on Russia’s state register of medicines. No Western pharmaceutical company has taken it through development.
Kolomin et al. (2013), writing from the developing institute, date the programme to the late 1970s under N.F. Myasoedov and I.P. Ashmarin, with the explicit goal of extending the 30–60 minute activity of ACTH(4-10). The Pro-Gly-Pro extension was chosen because glyprolines resist serum peptidases; the intermediate Glu-His-Phe-Pro-Gly-Pro formed in serum is itself reported to retain neurotrophic activity. “Semax 0.1%” nasal drops came first, and “Semax 1%” followed by 2001 for post-stroke use, according to the same authors. FDA’s 2026 review confirms that 0.1% and 1% nasal drops are on the Russian State Register of Medicines.
Semax has no USAN or INN, no USP or NF monograph, and no monograph in the European, Japanese or International Pharmacopoeias. FDA noted that both nominators’ certificates of analysis mixed free-base and acetate identifiers, one reason it judged neither form well characterised. No US patent held by a pharmaceutical developer was verified for this article, so none is listed.
What the data say
The research falls into two groups. The first is animal work, mostly in rats, where Semax given into the nose or by injection has been studied after blocked blood flow to the brain and in tests of memory, pain, mood and blood clotting. These studies report protective effects and changes in brain growth-factor genes, and almost all come from the developer’s own institute.
The second group is human studies. These are mostly small, mostly published in Russian, and often lack a placebo group or blinding. They include stroke patients, people with migraine or facial nerve pain, healthy volunteers and children. The FDA reviewed the English-language evidence in 2026 and found it insufficient to show effectiveness for any use it examined. No trial is registered on ClinicalTrials.gov.
All human exposure identified by FDA (2026) was intranasal: roughly 33–47 healthy adults, 69 adults with medical conditions (chronic cerebral ischaemia, migraine, trigeminal neuralgia, peptic ulcer) and 451 children with depression or tics, several reported only as meeting abstracts. Koroleva et al. (1996) gave a single 0.5 mg/kg intranasal dose to 12 adults with migraine; 4 of 12 reported the headache stopping at 90–120 minutes, with no control group or blinding. Gusev et al. (2018, in Russian, n=110 after ischaemic stroke) reported higher plasma BDNF and better Barthel index scores with two 10-day courses of 6,000 µg/day, in subgroups without stated randomisation or blinding.
Most cerebral-ischaemia trials exist only in Russian and were set aside by FDA under its translation rule. No study used subcutaneous injection, and there are no human pharmacokinetic data. FDA concluded that the evidence was insufficient to show effectiveness for cerebral ischaemia, migraine or trigeminal neuralgia. Independent replication outside the developer’s institute is limited.
Regulatory picture
Approval: no medicine containing Semax is approved by the FDA, and registration in Russia does not carry over to the United States. Compounding: in September 2023 the FDA put Semax in “Category 2”, the group of substances pharmacies should not compound from, citing possible immune reactions and impurities. By April 2026 the FDA listed it as withdrawn from that category by its nominators, and FDA staff then reviewed it on the agency’s own initiative. In July 2026 an FDA advisory committee voted narrowly to recommend adding Semax to the list of allowed compounding ingredients, even though FDA staff had advised against it. The vote is not binding, and the FDA had not made a final decision when this was written. Enforcement: FDA warning letters to two compounding businesses, in 2020 and 2021, named Semax among ingredients they should not have compounded.
Approval: none. No US IND-stage programme could be verified.
Compounding: “Semax (heptapeptide)” entered Category 2 of the interim 503A policy on 2023-09-29. FDA’s safety-risk page (updated 2026-04-22) lists it among substances withdrawn by the nominators, and it appears in no category of FDA’s 503A nominations list updated 2026-05-14. It is not on the 503A bulks list (21 CFR 216.23), so this article records compounding status as unknown.
FDA’s briefing document (dated 2026-05-11) evaluated the free base and acetate for cerebral ischaemia, migraine and trigeminal neuralgia and concluded that the criteria weigh against inclusion. It cited incomplete characterisation (impurities, aggregates, endotoxin), immunogenicity concerns for injectable and nasal products, missing information on nasal-spray container and pump systems, possible bleeding risk and dopaminergic effects in rodents, and insufficient efficacy data. On 2026-07-24 the Pharmacy Compounding Advisory Committee nonetheless voted in favour; published accounts give the tally as 8 votes to 5, and official minutes had not been posted when this was written. Notice-and-comment rulemaking is required before inclusion takes effect.
