Semax 10mg Peptide

Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues are ACTH(4-7), the core of the adrenocorticotropic hormone fragment 4-10 that had been known since the 1960s to affect learning in rodents. The last three, Pro-Gly-Pro, replace ACTH residues 8-10 (Arg-Trp-Gly). That single substitution is the whole design: it removes the part of the molecule that talks to the adrenal cortex while keeping the part that acts in the brain, and the proline-rich tail slows the aminopeptidases and carboxypeptidases that destroy the unmodified fragment in under a minute.

The peptide came out of the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow, working with the Faculty of Biology at Lomonosov Moscow State University, and the same group has published most of what is known about it. It is registered as a medicine in the Russian Federation, sold as nasal drops at two strengths, 0.1% (1 mg/mL) and 1% (10 mg/mL). No regulator outside the post-Soviet states has evaluated it, and as of August 2026 a query of ClinicalTrials.gov for Semax returns zero registered studies.

That combination is unusual and it is what makes the compound worth reading carefully about. There is a real clinical file behind Semax, but it sits almost entirely in Russian-language journals from one institutional cluster, largely predates trial pre-registration, and is not represented in the registries a Western reader would check first. The molecular and preclinical work, by contrast, is well characterised, reproducible and published in English, and that is where the specific numbers on this page come from.

The most replicated finding is that Semax raises brain-derived neurotrophic factor and the expression of its receptor. In rat hippocampus, a single intranasal application at 50 µg/kg produced a maximal 1.4-fold rise in BDNF protein, a 1.6-fold rise in TrkB tyrosine phosphorylation, a 3-fold rise in exon III BDNF mRNA and a 2-fold rise in trkB mRNA, and the treated animals produced more conditioned avoidance reactions than controls (Dolotov and colleagues, Brain Research, 2006). Those four numbers describe four different things and are frequently collapsed into a single inflated percentage elsewhere. Protein rose by 40%. Transcript rose threefold. Both statements are true and they are not the same statement.

Membranes isolated from rat basal forebrain carry specific, saturable, reversible binding sites for tritium-labelled Semax, with a dissociation constant of 2.4 ± 1.0 nM and a Bmax of 33.5 ± 7.9 fmol/mg protein. Binding required calcium ions. In the same study, intranasal Semax at 50 and 250 µg/kg raised BDNF protein in basal forebrain within 3 hours but not in cerebellum, which argues that the effect is regionally targeted rather than a general trophic wash (Dolotov and colleagues, Journal of Neurochemistry, 2006). The identity of the binding protein has never been established, and no melanocortin receptor subtype has been shown to account for it. The receptor question for Semax is genuinely open.

Downstream of the neurotrophins, the peptide touches monoamines and fast ionotropic signalling. In rats given 0.15 mg/kg intraperitoneally, striatal tissue 5-HIAA rose 25% at 2 hours and extracellular 5-HIAA climbed to 180% of baseline over 1 to 4 hours, while dopamine and its metabolites did not move on their own. Given 20 minutes ahead of D-amphetamine, Semax sharply amplified the amphetamine-evoked dopamine release and locomotor response (Eremin and colleagues, Neurochemical Research, 2005). In isolated neurons, 1 µM Semax increased the amplitude of GABA-activated current in cerebellar Purkinje cells by 147 ± 13% and reduced glycine-activated chloride current in hippocampal pyramidal neurons to 68% of control at 0.1 µM and 43% at 1 µM, with both effects slow in onset and poorly reversible, which points to second messengers rather than direct channel binding.

A fourth strand is inorganic. The N-terminal Met-Glu-His motif gives Semax an ATCUN-like Cu(II) chelation site, and the resulting complex has a CuN4 chromophore that is redox-stable and unreactive toward ascorbic acid. In artificial membrane models, Semax both blocked formation of the amyloid-beta:Cu(II) complex and interfered with fibrillogenesis of the complex once formed. This is the least-discussed part of the pharmacology and it turns out to be the part that explains why the acetylated derivatives behave differently.

The neurotrophin story is the reason Semax is studied at all, and it was built in a specific order. The first observation was that the peptide kept neurons alive in culture. The hypothesis that followed was that it did so by inducing neurotrophic factors, and in 2001 glial cells cultured from the basal forebrain of newborn rats confirmed it: 30 minutes after exposure, BDNF mRNA was up eightfold and NGF mRNA fivefold over control. That is a cell-culture result at a saturating concentration and should be read as proof that the mechanism exists, not as the size of the effect in an animal.

The whole-animal version is smaller and more interesting. Twenty minutes after a single intranasal application in rats, Bdnf and Ngf transcript levels fell in hippocampus and rose in frontal cortex. By 40 minutes both had returned to control. By 90 minutes both had risen significantly again, and by 8 hours they were back at baseline. A biphasic, region-inverted time course is not what a simple trophic stimulant looks like, and it is why single-timepoint studies of Semax disagree with each other so often.

The receptor arm moves with the ligand arm. In hippocampus, TrkB tyrosine phosphorylation rose 1.6-fold at the same time BDNF protein rose 1.4-fold, and trkB mRNA rose 2-fold. A trophic factor whose receptor is not also upregulated tends to desensitise; here both sides of the pair respond, which is the mechanistic argument for why any behavioural effect was observed in the conditioned avoidance task at all.

Finally, the induction is conditional on injury. After permanent middle cerebral artery occlusion in rats, Semax raised Bdnf, TrkC and TrkA at 3 hours, Nt-3 and Ngf at 24 hours, and Ngf again at 72 hours, and a comparison across intact, sham-operated and occluded animals showed the effect was selective for ischaemic cortex. The Pro-Gly-Pro tripeptide administered on its own also altered neurotrophin transcription, but without that selectivity. The tail is not inert, and any account of Semax that treats Pro-Gly-Pro purely as a protecting group is incomplete.

The transient middle cerebral artery occlusion rat model is where the modern mechanistic work on Semax lives, and the readout has moved from single genes to whole transcriptomes. RNA-Seq of rat brain 24 hours after occlusion identified 394 genes differentially expressed by more than 1.5-fold in Semax-treated animals relative to saline. The direction is the point: ischaemia-reperfusion on its own activated inflammatory genes and suppressed neurotransmission genes, and Semax did the reverse of both. The authors frame the action as compensation for a disrupted expression pattern rather than as a novel stimulus.

A follow-up in the same model checked whether the transcript changes reached protein. At 24 hours after occlusion, active CREB was raised in subcortical structures including the damage focus, while MMP-9 and c-Fos were reduced in the adjacent frontoparietal cortex and active JNK was reduced in both tissues. The protein picture is consistent with the transcript picture rather than merely compatible with it, which is a stronger claim than most single-omics studies in this literature can make.

Work outside the brain has followed the same logic. A 2025 study in female mice reported that Semax acts on the mu opioid receptor gene Oprm1 to promote deubiquitination and limit lysosomal membrane permeabilisation after spinal cord injury, with functional recovery as the endpoint. That is a distinct mechanism from the neurotrophin one and has not been replicated independently, but it is the first Semax target proposed at the level of a named gene product outside the melanocortin and neurotrophin families.

A 2025 electrophysiology study narrowed one hypothesis by ruling it out. Semax at 1 µM increased the frequency of spontaneous intracellular calcium fluctuations in CA1 pyramidal cells but had no effect on proton-stimulated calcium entry in cerebellar granule cells, so the neuroprotective mechanism does not appear to run through attenuation of acid-sensing ion channels. Negative results of that specificity are rare here and worth more than another positive gene list.

Three related compounds circulate under confusingly similar names and buyers mix them up constantly. Semax is H-Met-Glu-His-Phe-Pro-Gly-Pro-OH: free amine at one end, free carboxylate at the other, C37H51N9O10S, 813.93 g/mol, CAS 80714-61-0, PubChem CID 9811102. N-Acetyl Semax is the same sequence with an acetyl group on the N-terminal methionine, C39H53N9O11S, roughly 855.97 g/mol. N-Acetyl Semax Amidate carries both the N-terminal acetyl and a C-terminal carboxamide in place of the carboxylic acid, C39H54N10O10S, 855.0 g/mol, CAS 2920938-90-3, PubChem CID 172638603. Acetylation adds 42.04 to the mass and amidation subtracts 0.98, which is why the acetylated and the doubly modified forms differ by only about one unit and are so easily transposed.

The naming problem is not only a supplier problem. PubChem's own synonym list for CID 172638603 carries both 'N-acetyl semax amidate' and the bare string 'N-acetyl semax'. A label reading N-Acetyl Semax therefore does not, on its own, tell you which of the two modified compounds is in the vial. Mass spectrometry does, and a one-dalton difference is well within the resolving power of the instruments that produce a certificate of analysis, so it is a reasonable thing to ask a supplier to confirm in writing.

The chemistry behind the modifications is straightforward and is almost never stated correctly. Aminopeptidases require a free alpha-amino group to begin cleaving from the N-terminus, and acetylation removes that handle. Carboxypeptidases require a free C-terminal carboxylate, and amidation removes that one. Proline resists most peptidases in the first place, which is why the Pro-Gly-Pro tail was chosen. On paper the derivatives are therefore harder to degrade. What does not follow is that they are more potent, and no head-to-head pharmacokinetic or efficacy comparison between Semax and either derivative has been published in the indexed literature. A PubMed search for N-acetyl semax amidate returns zero records.

There is one direct experimental comparison and it runs the other way. When N-terminal acetylation of Semax was studied against the parent peptide, acetylation changed the copper coordination geometry from a CuN4 chromophore to a distorted CuN3O with a weak apical methionine interaction, raised the formal redox potential of the complex, and left the complex reactive toward ascorbic acid where the non-acetylated form is redox-stable. In SH-SY5Y neuroblastoma cells, acetylated Semax did not protect against Cu(II)-induced toxicity, and the authors attributed the protection seen with the parent compound specifically to its free N-terminal amine. Zinc binding was unaffected by acetylation. Blocking the N-terminus buys resistance to aminopeptidases and costs the copper chemistry that carries at least one documented protective effect. That trade is what the promotional descriptions leave out.

The half-life figures attached to these compounds in circulation deserve corresponding care. Published values for Semax cluster in the range of minutes, consistent with the degradation kinetics described below, while figures of two to ten hours appear widely with no pharmacokinetic citation and appear to be duration of perceived effect restated as a plasma parameter. They are different quantities, and for an intranasally delivered neuropeptide whose transcriptional effects outlast the molecule by hours, the plasma number on its own is close to uninformative.

Semax and Selank share a design principle and little else. Both came from the same Moscow institute, and both were built by attaching Pro-Gly-Pro to a bioactive parent fragment to keep peptidases off it. The parent fragments are unrelated. Semax carries ACTH(4-7), Met-Glu-His-Phe, a melanocortin sequence. Selank carries tuftsin, Thr-Lys-Pro-Arg, an immunomodulatory fragment of the IgG heavy chain, giving Thr-Lys-Pro-Arg-Pro-Gly-Pro at 751.9 g/mol under CAS 129954-34-3.

The pharmacology diverges accordingly. Semax is studied for neurotrophin induction, ischaemic neuroprotection and cognitive endpoints. Selank is studied for anxiolytic-like activity and for effects inherited from tuftsin on immune signalling. Where the two have been examined side by side the results separate cleanly: in rats with 6-hydroxydopamine lesions of the substantia nigra, neither peptide altered motor activity in the elevated maze or passive defensive behaviour, but Selank alone reduced anxiety measures. Sharing a stabilising tail does not make two peptides interchangeable, and a result obtained with one is not evidence for the other.

This catalogue lists Semax and Selank as separate items and also lists a combined Selank plus Semax vial. The combined vial removes one reconstitution variable from co-administration work, but it cannot support dose-response work on either peptide alone because the two are present at fixed proportion. Where a design calls for varying one compound against a fixed background of the other, the single-compound vials are the correct choice.

The primary kinetic measurement uses Semax tritiated at the C-terminal proline, given intranasally at 50 µg/kg in a 20 µL volume to white rats of 200 to 250 g. Two minutes after administration, 0.093% of the total administered radioactivity per gram was recoverable from brain, and 80% of that radioactivity was still intact Semax. The remaining 20% was already metabolites, at two minutes. This is the number that anchors any honest statement about how fast the molecule disappears.

The dominant degradation product is Pro-Gly-Pro itself. Across biological samples the tripeptide predominates relative to the combined content of Semax and its other metabolites, which is the expected outcome of sequential cleavage from the N-terminal end down toward a proline-resistant tail. Pro-Gly-Pro is not an inert leftover: administered alone it alters neurotrophin and receptor transcription in rat cortex, though without the ischaemia-selectivity that Semax shows. Any pharmacokinetic account that stops at 'rapidly degraded' has skipped the part where the degradation product has pharmacology of its own.

Two things follow. First, plasma half-life is a poor guide to anything here. The molecule is measured in minutes while the transcriptional consequences, the BDNF and NGF mRNA changes, run over 90 minutes to 8 hours in rat brain, and the plasma BDNF elevation reported in the post-stroke cohort persisted across a five month observation period. Second, intranasal delivery is not a stylistic preference in this literature. It is how essentially all of the in vivo work was done, and results obtained by that route cannot be assumed to transfer to another.

Human pharmacokinetic data are effectively absent. No plasma concentration-time curve for Semax in humans appears in the indexed literature, which is why the detailed numeric pharmacokinetic tables circulating for both Semax and its amidate derivative cannot be traced to a source. Where a figure has no measurement behind it, the accurate answer is that the measurement has not been published.

Semax is a registered medicine in the Russian Federation and is supplied there as nasal drops in two strengths. The 0.1% preparation contains 1 mg of peptide per millilitre and the 1% preparation contains 10 mg per millilitre, and the two carry different approved indications rather than being simple tenfold variants of one another: the higher strength is associated with acute ischaemic cerebrovascular indications, while the lower strength covers cognitive indications and a set of ophthalmic ones including optic nerve atrophy and optic neuritis. Registration dates to the 1990s. No regulator in the United States, the European Union, the United Kingdom, Canada or Australia has assessed the compound.

The clinical literature behind that registration has a specific shape and it is worth stating plainly. It is overwhelmingly single-country and largely single-institute, published mostly in Russian-language journals, mostly predating trial pre-registration norms, and not represented in international trial registries. A query of ClinicalTrials.gov for Semax as of August 2026 returns no records at all, whether searched as an intervention or as a general term. That is not evidence that no research was done, and it is not evidence of quality either. It means the usual Western verification path does not exist for this compound and a reader has to go to the primary papers.

The best-documented of those papers followed 110 patients after ischaemic stroke, 43 men and 67 women, mean age 58.0 ± 9.7 years, split into early rehabilitation (89 ± 9 days) and late rehabilitation (214 ± 22 days) groups, each further divided into subgroups that did and did not receive the peptide. The regimen was two ten-day courses of intranasal 1% Semax at 6000 µg daily, separated by a 20 day interval. Plasma BDNF rose in the treated subgroups and stayed elevated across the study, Barthel index recovery was faster and final scores higher, and plasma BDNF correlated with Barthel score with the correlation modified by rehabilitation timing. The report describes neither randomisation nor placebo control nor blinding, so it is a controlled observation rather than a controlled trial.

The one properly placebo-controlled human study located is small and mechanistic rather than clinical. Twenty-four healthy volunteers of mean age 43.9 ± 9.5 years underwent resting-state fMRI at baseline and at 5 and 20 minutes after intranasal 1% Semax (14 subjects) or placebo (10 subjects). The Semax group showed a larger rostral, medial frontal cortex subcomponent of the default mode network. It demonstrates that a single intranasal administration produces a measurable change in brain network topography within minutes. It demonstrates nothing about outcomes.

One frequently repeated claim deserves a precise answer. Semax is described everywhere as having no corticotropic activity, and the structural basis for that is sound: the ACTH(8-10) region required for activity at MC2R on the adrenal cortex is not present, having been replaced by Pro-Gly-Pro. What does not exist, as far as the indexed literature shows, is a human study that measured plasma or salivary cortisol after administration. The absence of the corticotropic pharmacophore is a structural fact. 'Does not engage the hypothalamic-pituitary-adrenal axis' is a broader claim with no published measurement behind it, and it sits awkwardly next to the rodent chronic-stress work in which Semax reversed stress-induced adrenal hypertrophy, an HPA-adjacent result in the opposite direction.

Semax carries a free N-terminal methionine, the most oxidation-prone residue in the sequence, and the thioether converts to methionine sulfoxide on exposure to air, light and oxidising trace metals. Oxidation adds 16 daltons, is visible by mass spectrometry, and matters mechanistically rather than cosmetically, because the same N-terminal region carries the copper coordination site. Acetylation of the N-terminal amine does not protect the thioether, so this pathway applies equally to the modified derivatives. Amber or opaque containers, minimal headspace and an inert atmosphere are the reason behind the 'protect from light' line that most handling notes give without explanation.

Purity on a certificate of analysis is normally reported as HPLC area percent, and it is worth knowing what that figure does not cover. Area percent at a single UV wavelength will not resolve a D-histidine epimer from the L form, will not necessarily separate deletion sequences that co-elute with the target, and says nothing at all about identity without an accompanying mass. Deletion and truncation sequences are the characteristic impurity class in solid-phase synthesis of a short proline-rich peptide, so the informative combination is chromatographic purity plus a measured mass within a stated tolerance of 813.93 for the free acid.

Peptide content is the other number that changes the arithmetic. A lyophilisate contains counter-ion, residual water and residual solvent as well as peptide, and net peptide content specifications in the 80% range are ordinary for this class. A vial labelled 10 mg therefore need not contain 10 mg of peptide, and the difference propagates directly into any molar calculation for in vitro work. Residual trifluoroacetate from purification is a separate consideration for cell assays, where it has documented effects of its own at concentrations a synthesis routinely leaves behind.

Identity confirmation for Semax is a solved analytical problem. A validated liquid chromatography tandem mass spectrometry method covering ten putative cognitive-enhancing research peptides, Semax and Selank among them, was published in 2020 after seized pharmaceutical preparations were found to contain both, and it was validated in several matrices to ISO 17025 under the European Official Medicines Control Laboratory network's screening guidance. The method is in the public literature, which means an independent laboratory can verify a sample without developing anything new.