Semax is a synthetic heptapeptide built from the ACTH(4-7) fragment (Met-Glu-His-Phe) with a C-terminal Pro-Gly-Pro tail added to slow enzymatic breakdown. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences and has been used clinically in Russia since the 1990s, where it is registered as a drug for ischemic stroke and cognitive impairment.12It is not an approved drug in Canada, the United States, or the EU, and is offered here strictly for research use only (RUO). Most clinical data come from older, relatively small Russian studies; the supporting mechanistic work is predominantly in rodent models. Figures below are reported as published; values that are not well established are flagged as such.
Sequence & identity
Linear heptapeptide; identity per PubChem CID 122178 (InChIKey AFEHBIGDWIGTEH-CXFOGXNKSA-N).5
Mechanisms studied
Researchers report that Semax is an analog of the ACTH(4-10) melanocortin fragment that lacks the corticotropic activity of the parent hormone. In rat models, a single intranasal dose (50 µg/kg) was reported to raise hippocampal BDNF protein roughly 1.4-fold and exon-III BDNF mRNA about 3-fold, alongside increased trkB receptor phosphorylation, an effect researchers link to CREB-dependent transcription.3 In a permanent middle-cerebral-artery occlusion model, Semax was reported to enhance transcription of BDNF, NGF and their Trk receptors in ischemic cortex and to blunt the ischemia-associated decline in receptor expression.4 Reported additional actions include modulation of dopaminergic and serotonergic systems and inhibition of enkephalin-degrading enzymes. The peptide is rapidly degraded after administration (its plasma persistence is reported to be on the order of minutes) to fragments such as EHFPGP, HFPGP and Pro-Gly-Pro, which have themselves been studied as active metabolites.6
Dosing in the research literature
The figures below summarise regimens as reported in published research — they are not recommendations or directions for use.
| Source / model | Regimen reported | Notes |
|---|---|---|
| Gusev, Skvortsova et al., 1997 (acute ischemic stroke, human; PMID 11517472)2 | Intranasal, 12 mg/day reported for moderate stroke and 18 mg/day for severe stroke, over 5- and 10-day courses. | Russian clinical study in 30 treated patients vs 80 controls; reported as research findings, not a usage recommendation. No approved dosing exists in Canada/US. |
| Kaplan et al., 1996 (healthy human cognition; Neurosci Res Commun 19:115-123)1 | Single intranasal application reported in the 0.25-1.0 mg range in the attention/performance testing studies. | Small healthy-subject study; exact protocols vary across the Russian literature. Cited for research context only. |
| Dolotov et al., 2006 (rat mechanism; PMID 16996037)3 | Single intranasal dose of 50 µg/kg in rats. | Animal pharmacology dose used to measure BDNF/trkB changes; not translatable to a human regimen. |
Effects observed in research
In healthy human subjects, an early study reported that intranasal Semax improved attention and short-term memory during testing and produced EEG changes the authors compared to known neuroactive agents.1 In acute ischemic stroke, a Russian clinical study reported that adding Semax to standard therapy was associated with faster regression of motor and general cerebral symptoms, supported by EEG mapping and evoked-potential measures.2 In rodent studies, researchers observed effects on learning and memory tasks and neuroprotective and anti-inflammatory activity in ischemia models, which they attributed in part to upregulated neurotrophin (BDNF/NGF) signaling.34 These are reported research findings in specific models and human studies; they are not established therapeutic outcomes in any approved indication.
Strength of evidence
Grade B. Semax has more human data than most research peptides: it has been used in Russian clinical practice for decades and is the subject of multiple human reports in stroke and cognition, plus a substantial mechanistic literature in rodents (BDNF/NGF, trkB, neuroprotection).1234 However, the clinical trials are generally older, small (e.g. ~30 treated patients in the cited stroke study), single-region, and not replicated in large blinded Western RCTs, and much of the source literature is in Russian. There is no FDA or Health Canada approval. The strongest, most reproducible findings are the animal-model neurotrophic effects; human efficacy claims should be treated as preliminary.
Reconstitution & storage
Reconstitute with bacteriostatic water for laboratory handling. Store lyophilised material frozen and reconstituted material refrigerated. Use Peptigo’s reconstitution calculator and storage cheat sheet for working figures.
References
- Kaplan AYa, Kochetova AG, Nezavibathko VN, Rjasina TV, Ashmarin IP. Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neuroscience Research Communications. 1996;19(2):115-123. doi:10.1002/(SICI)1520-6769(199609)19:2<115::AID-NRC171>3.0.CO;2-B
- Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat’ko VN, Zhuravleva EIu, Vanichkin AV. Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. PMID 11517472.
- Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research. 2006;1117(1):54-60. doi:10.1016/j.brainres.2006.07.108. PMID 16996037.
- Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2010;30(1):71-79. doi:10.1007/s10571-009-9432-0. PMID 19633950. PMC11498467.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 122178, Semax. https://pubchem.ncbi.nlm.nih.gov/compound/122178 (accessed 2026-06-03).
- Shevchenko KV, Nagaev IIu, Alfeeva LIu, et al. Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration. Russian Journal of Bioorganic Chemistry (Bioorg Khim). 2006;32(1):64-70. doi:10.1134/S1068162006010055. PMID 16523722.