What Is Semax? Definition and What Research Reports

Semax in plain language

Semax is the name given to a short, laboratory-made peptide — a chain of seven amino acids — that was designed in Russia by copying a small piece of a natural human hormone and adding a short tail to make it last longer in the body. The piece it copies comes from adrenocorticotropic hormone (ACTH), but the copied fragment is the part that does not trigger cortisol release, so Semax is generally described in the literature as a "non-hormonal" ACTH fragment analogue. It is most often discussed in the context of brain research: laboratory studies have examined it in animal models of stroke, memory impairment, and neurodegeneration. It is not an approved drug in the United States or the European Union.

What Semax is in biochemical terms

Semax is usually written as ACTH(4-7)-PGP or Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues correspond to positions 4 through 7 of ACTH; the appended Pro-Gly-Pro (PGP) tripeptide is a protective C-terminal extension that slows enzymatic degradation. Because of this design, Semax is frequently grouped with "ACTH(4-10) analogues" in the older literature, and papers often carry both descriptions in the same title — for example, a rodent neurochemistry paper described it as "an ACTH(4-10) analogue with nootropic properties" (PMID 16362768). The PGP fragment is itself biologically active and has been studied alongside Semax as a separate comparator (PMID 19633950).

Semax is described as a regulatory peptide rather than a receptor-specific drug in the classical sense. Much of the published mechanistic work is transcriptional: researchers have profiled the genes whose expression changes in brain tissue after administration in ischemia models, rather than identifying a single binding target. One 2025 report did nominate a specific molecular target, describing effects on the μ-opioid receptor gene Oprm1 and on protein deubiquitination in a mouse spinal cord injury model (PMID 40692165).

Regulatory status of the name

"Semax" functions as both a research designation and, in some jurisdictions, a registered pharmaceutical trade name. It is registered as a medicine in Russia, where most of its clinical development took place; it has not been approved by the U.S. Food and Drug Administration or the European Medicines Agency, and it is not an ingredient permitted in dietary supplements in the United States. Material sold under the name elsewhere is typically labelled "research use only" (RUO), a designation that indicates the product is not intended for human or veterinary use and has not been evaluated for purity, sterility, or identity as a medicine. This page is for educational purposes only and is not medical advice; consult a licensed physician about any health question or medication decision.

How the term is used in peptide research

In the peer-reviewed literature, "Semax" almost always appears in one of four contexts:

• Cerebral ischemia models. Rodent middle cerebral artery occlusion and ischemia-reperfusion experiments form the largest single cluster of published work (PMID 32580520).
• Learning and memory tasks. Behavioural studies in rats have paired Semax with amnesia-inducing insults to test whether task performance is preserved (PMID 27411820).
• Neurotransmitter and gene-expression pharmacology. Papers measuring monoamine systems or neurotrophin transcription (PMID 16362768).
• Neurodegeneration and injury models. Parkinson-like, Alzheimer-like, and spinal cord injury paradigms (PMID 28702721).

Where the term is misused

Several loose usages appear outside the literature and are worth flagging in a definition:

• "Semax is a nootropic drug." "Nootropic properties" is a descriptor used in preclinical rodent titles (PMID 16362768); it is not a regulatory category, and it does not indicate demonstrated cognitive benefit in healthy humans.
• "Semax is an ACTH hormone." Semax is a fragment analogue. The published framing consistently treats it as lacking the corticotropic activity of full-length ACTH.
• Conflation with Selank. Selank is a structurally unrelated tuftsin analogue. The two are frequently discussed together because Russian groups studied them in parallel — for example in a functional connectomic comparison (PMID 32342318) and in a 6-OHDA parkinsonism behaviour study (PMID 28702721) — but they are distinct compounds.
• Treating animal-model results as human outcomes. Nearly all the work summarised below was conducted in rats or mice.

Related terms

What the published literature reports

Cerebral ischemia

A rat study of experimental ischemic infarction of the cerebral cortex reported neuroprotective and antiamnesic effects of Semax in that model (PMID 17603664). Separately, researchers examined transcription after cerebral ischemia and reported that both Semax and Pro-Gly-Pro activated transcription of neurotrophins and their receptor genes (PMID 19633950). A later transcriptome-wide analysis following cerebral ischaemia-reperfusion in rats described protective properties of the peptide at the gene-expression level (PMID 32580520).

Learning, memory and behaviour

In a heavy-metal exposure paradigm, the study reported that Semax prevented inhibition of learning and memory in the animals tested (PMID 27411820). In a 6-hydroxydopamine model of Parkinson-like parkinsonism, researchers reported that both Semax and Selank affected the behaviour of the treated rats (PMID 28702721).

Neurochemistry and network-level measures

A rodent neurochemistry paper reported activation of dopaminergic and serotoninergic brain systems (PMID 16362768). A functional connectomic approach was later applied to compare the effects of Selank and Semax at the level of brain network organisation (PMID 32342318).

Neurodegeneration and injury models

A 2025 paper examined Semax and a derivative for correcting pathological impairments in an animal model of Alzheimer's disease (PMID 41479572). In female mice after spinal cord injury, researchers reported that Semax targeted the μ-opioid receptor gene Oprm1, promoted deubiquitination, and was associated with functional recovery in that model (PMID 40692165).

Safety and Adverse Events: What Studies Report

The verified literature summarised here contains no human safety trials, no adverse-event tables, and no tolerability reporting. Two animal papers touched on non-neurological tissue effects. One examined the morphofunctional state of hepatocytes under chronic emotional and painful stress in animals given ACTG(4-7)-PGP (Semax), reporting an influence on liver cell morphology in that stress model (PMID 28577097). Another reported anticoagulation and antiplatelet effects of Semax under conditions of acute and chronic immobilization stress (PMID 21113455). Effects on coagulation and platelet function are pharmacologically relevant observations, but they were measured in stressed rodents and were not framed as human safety findings.

Limitations of the evidence base

1. The great majority of published work is preclinical, conducted in rats or mice under induced-injury conditions rather than in healthy subjects.
2. Many studies originate from a small number of research groups, which limits independent replication.
3. Outcome measures are often transcriptional or behavioural surrogates rather than clinical endpoints.
4. Sex, species and model differences matter — the spinal cord injury work was reported in female mice specifically (PMID 40692165).
5. Regulatory approval in one country does not transfer to others, and does not substitute for independent evidence.

References

• Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents (Neurochemical Research, 2005)
• Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex (Bulletin of Experimental Biology and Medicine, 2006)
• Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia (Cellular and Molecular Neurobiology, 2010)
• Anticoagulation and antiplatelet effects of semax under conditions of acute and chronic immobilization stress (Bulletin of Experimental Biology and Medicine, 2010)
• Semax prevents learning and memory inhibition by heavy metals (Doklady Biological Sciences, 2016)
• Influence of ACTG(4-7)-PGP (Semax) on Morphofunctional State of Hepatocytes in Chronic Emotional and Painful Stress (Bulletin of Experimental Biology and Medicine, 2017)
• Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like parkinsonism (Doklady Biological Sciences, 2017)
• Functional Connectomic Approach to Studying Selank and Semax Effects (Doklady Biological Sciences, 2020)
• Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats (Genes, 2020)
• Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice (British Journal of Pharmacology, 2025)
• The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease (Acta Naturae, 2025)