Semax: what the research literature shows

What it is

Origin

ACTH is a peptide hormone, and residues 4 to 10 of it, written ACTH(4-10), form a fragment that a 1993 paper calls behaviourally active.² That paper, on the breakdown of the fragment and of its synthetic analogue Semax, came from the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow.²

Review A 1997 review, whose title speaks of 15 years of experience in the design and study of Semax, calls it one of the rare analogues of regulatory peptides to pass from basic research into practical use.¹⁵

Sequence and chemistry

Values are from the two PubChem records.¹¹⁶

Only the first four residues are shared, so some papers write the name as ACTH(4-7)PGP.¹⁰¹⁷ The molecule has free ends, one acidic side chain, a histidine and a methionine at the N-terminus.¹

The Pro-Gly-Pro tail

Review A 2005 paper that shares several authors with the 1997 review describes glyprolines and other short peptides that contain Pro-Gly-Pro as about as stable as major pharmacological preparations.⁵ It presents Semax and Selank as hybrids in which pieces of natural regulatory peptides help to stabilize the whole molecule in the body.⁵ The abstract states this as a concept and reports no measurements.⁵ The general idea is set out in our guide to half-life extension strategies.

Cell study The tail does not make the peptide immune to enzymes. In rat serum, both ACTH(4-10) and Semax were broken down, and inhibitor experiments attributed most of the hydrolysis of both to aminopeptidases and angiotensin-converting enzyme.² That abstract gives no rate for either peptide.² With plasma membranes from rat brain, the half-life of Semax was longer than one hour, and enzymes removed residues from the N-terminus to leave the pentapeptide His-Phe-Pro-Gly-Pro and then Pro-Gly-Pro itself.⁶

How it is studied

Three kinds of experiment recur, and they sit on different rungs of the evidence ladder.

• Cell study Bench and cell work: binding of tritium-labelled peptide to rat brain membranes, with HPLC to follow the fragments;⁶ and cultured rat glial cells, in which neurotrophin mRNA is measured.⁷
• Animal study Rodent work: healthy rats, in which BDNF, nerve growth factor (NGF) and trkB are measured and avoidance learning is scored;⁸¹⁸ and stroke models made by blocking the middle cerebral artery permanently or temporarily, read out with genome-wide expression analysis, RNA sequencing and protein assays.⁹¹⁰¹⁷
• Human study Clinical work: stroke patients followed with neurological scales, EEG and plasma BDNF;¹⁹²⁰ and healthy volunteers scanned with resting-state functional MRI.²¹

What the literature reports

Binding sites

Cell study Tritium-labelled Semax bound to membranes from the rat basal forebrain in a way that was time-dependent, specific, reversible and dependent on calcium ions, with a dissociation constant of about 2.4 nM.⁶²² Neither abstract names the receptor.⁶²² One group calls Semax a synthetic melanocortin derivative;¹⁰ that hormone family is described in our overview of melanocortin peptide research.

BDNF and other neurotrophins

BDNF is a protein that modulates how synapses change with use, and trkB is its receptor.⁸²²

Cell study In glial cells cultured from the basal forebrain of newborn rats, BDNF mRNA was about eight times the control level and NGF mRNA about five times, 30 minutes after Semax was added.⁷

Animal study In rats, Semax was followed three hours later by higher BDNF protein in the basal forebrain but not in the cerebellum.²² In the hippocampus, after a single administration, the same group reported a rise of up to 1.4-fold in BDNF protein, a 1.6-fold rise in trkB phosphorylation, two- to three-fold rises in the matching mRNAs, and more conditioned avoidance responses.⁸

Animal study The direction was not uniform. A time-course study running from 20 minutes to 24 hours found that expression of both the BDNF and the NGF gene fell in the hippocampus and retina at 20 minutes and rose in the frontal cortex.¹⁸

Monoamines

Animal study In rodents, Semax alone raised the serotonin metabolite 5-HIAA in the striatum without changing dopamine or its metabolites.²³ Given before amphetamine, it amplified the dopamine and locomotor response to that drug.²³

Ischemia models

Animal study After permanent occlusion of the middle cerebral artery in rats, Semax raised transcription of several neurotrophin and neurotrophin-receptor genes in the cortex at time points from 3 to 72 hours.⁴ Pro-Gly-Pro alone also changed some of them, though the authors judged its influence mainly unspecific.⁴

Animal study A genome-wide expression study in the same model found that immune-response genes made up more than half of the genes Semax altered at 24 hours, with immunoglobulin and chemokine genes prominent and mostly raised.⁹

Animal study After temporary occlusion, RNA sequencing found 394 genes expressed differently in Semax-treated and saline-treated rats at 24 hours.¹⁰ Ischemia alone had raised inflammation genes and lowered neurotransmission genes, and Semax moved both sets the other way.¹⁰ A follow-up measured proteins: more active CREB in subcortical tissue, less MMP-9 and c-Fos in nearby cortex, and less active JNK in both.¹⁷

Animal study The two transcriptome studies appear to point in different directions for immune and inflammation genes; they used different models, and the abstracts do not reconcile them.⁹¹⁰ In a model of focal ischemia induced by light in the prefrontal cortex, a multi-day course of Semax was followed by a smaller cortical infarct and better retention of a passive avoidance response.²⁴

Human evidence

Human data exist, but they are thin. PubMed holds 208 records with Semax in the title or abstract; at least 96 share one author, 87 are written in Russian, and four are indexed as clinical trials.³ For the Russian papers below we read the abstracts, not the full text.

• Human study Acute stroke, 1997. Thirty patients with hemispheric ischemic stroke received Semax on top of intensive therapy and were compared with 80 patients on conventional therapy.¹⁹ The authors reported some influence on the rate of neurological recovery, motor deficits above all.¹⁹ The abstract calls the control group similar in severity and lesion site and mentions no randomization, blinding or placebo.¹⁹
• Human study Stroke rehabilitation, 2018. One hundred and ten patients were split by early or late rehabilitation and then by whether they received Semax.²⁰ Plasma BDNF rose and stayed high in those given Semax, and the authors reported faster gains on the Barthel index.²⁰ The abstract does not say how patients were allocated and mentions no placebo.²⁰
• Human study Motor neuron disease, 2007. In a study of 27 patients that PubMed indexes as randomized and the abstract calls open-label, Semax had no influence on electromyographic measures of denervation or on clinical rating scales; a quality-of-life total rose, which the authors put down to emotional state and motivation.²⁵
• Human study Healthy volunteers, 2018. In 24 volunteers, 14 given Semax and 10 given placebo, resting-state functional MRI showed a larger frontal subcomponent of the default mode network in the Semax group.²¹ The abstract reports no test of memory, attention or any other behaviour.²¹

Review The 1997 review makes broad claims about memory and attention in healthy men and about the absence of adverse effects, but its abstract gives no study designs, group sizes or results, so those claims cannot be weighed here.¹⁵ A search of ClinicalTrials.gov on 8 October 2026 for Semax as an intervention returned no registered study.²⁶

Regulatory status

• Russia. The government’s list of vital and essential medicines, approved by decree No. 3867-r of 18 December 2025, includes the peptide under its chemical name, in the group headed other psychostimulants and nootropic agents.¹¹ We could not search the Russian State Register of Medicines, so we state no registration number or approved uses.
• Canada. A search of Health Canada’s Drug Product Database on 8 October 2026 for Semax as an active ingredient returned no products.¹² A Health Canada advisory of 9 April 2026 on unauthorized injectable peptide drugs does not name Semax among its examples; it states that a “For Research Use Only” label does not make such products legal or exempt them from regulatory requirements.²⁷
• United States. A search of the FDA’s approved-drug data on the same day returned no matches.¹³ An FDA page on compounding, current as of 22 April 2026, lists “Semax (heptapeptide)” among bulk substances that were once in category 2 of its interim policies, the category for substances that may present significant safety risks, and were later withdrawn by their nominators.²⁸ The entry says that compounded drugs containing it may pose a risk of immunogenicity because of possible aggregation and peptide-related impurities, and that the agency has no, or limited, safety-related information.²⁸
• European Union. The European Commission’s Union Register, which lists centrally authorized medicines, had no entry for Semax among its active or its no-longer-active products on 8 October 2026.¹⁴ The register does not cover medicines authorized by single member states, which we did not check.

Material sold on this site is for laboratory research use only.

In the laboratory

Semax is supplied here as a lyophilized powder in sealed vials. A pre-mixed liquid format is also listed.

Mass is the first identity check. PubChem gives a molecular weight of 813.9 g/mol and a monoisotopic mass of 813.35 Da for the free peptide, so a mass spectrum, where a batch document gives one, should be consistent with those figures.¹ Batch documents are posted on the Lab Results page when they exist.

Two features bear on stability. The first is the methionine at the N-terminus.¹ Methionine is one of the residues usually watched for oxidation, which is explained with the other routes in peptide stability and degradation.

Cell study The second feature is enzymatic. Rat serum and rat brain membranes cut Semax into shorter peptides, so an assay run in serum-containing medium may be measuring fragments as well as the parent peptide.²⁶ The fragments may not be neutral by-products: Pro-Gly-Pro alone changed gene transcription in the rat stroke model.⁴

For temperature, light and moisture, sealed and once opened, follow the peptide storage guide.