Semax

A synthetic heptapeptide based on the ACTH(4-10) fragment, researched for nootropic and neuroprotective effects, with a recurring focus on brain-derived neurotrophic factor (BDNF) signalling.

What it is

Semax is a short synthetic peptide derived from the 4-10 fragment of adrenocorticotropic hormone (ACTH), with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP). The native ACTH(4-7) core is extended at the C-terminus with a Pro-Gly-Pro tripeptide, a modification that markedly improves resistance to enzymatic breakdown while stripping away the steroidogenic hormonal activity of the parent fragment. The result is a non-hormonal analogue: a heptapeptide of seven amino-acid residues that retains central nervous-system activity without stimulating the adrenal cortex.

Semax belongs to the family of neuro-active research peptides developed in Russia, alongside its sibling Selank. It was first described in the scientific literature in 1991 and is registered in Russia as a nootropic and neuroprotective agent (ATC code N06BX), appearing on the Russian List of Vital and Essential Drugs. It has not been evaluated or approved by the FDA or most other national regulators. Supplied strictly for laboratory research use only, not for human or veterinary use.

How it works

The most studied mechanism is modulation of the neurotrophin system, in particular BDNF and its receptor tyrosine kinase trkB. In the rat hippocampus, Dolotov and colleagues showed that a single dose of Semax raises both BDNF protein and the phosphorylation (activation) of trkB, alongside larger increases in BDNF and trkB messenger RNA. This positions Semax as an upstream regulator of the BDNF/trkB axis that supports synaptic plasticity, neuronal survival and memory consolidation. A companion study demonstrated that Semax binds specifically and reversibly to basal-forebrain cell membranes with a dissociation constant in the low nanomolar range, consistent with a defined molecular target rather than a purely diffuse effect.

Beyond neurotrophins, Semax has additional reported actions relevant to neuroprotection. It behaves as an inhibitor of enkephalin-degrading enzymes, prolonging the action of endogenous regulatory peptides, and its C-terminal Pro-Gly-Pro fragment is itself biologically active. In cerebral-ischaemia models, genome-wide analyses show Semax shifting the expression of immune, vascular and neurotrophic gene programmes, including upregulation of vascular endothelial growth factor and chemokine signalling that favour tissue survival and repair. Together these pathways underlie the nootropic and neuroprotective effects that dominate the research literature.

What the research shows

The quantitative backbone of the Semax literature is its effect on the hippocampal BDNF/trkB system. In Wistar rats, a single intranasal dose of 50 micrograms per kilogram produced a maximal 1.4-fold increase in BDNF protein and a 1.6-fold increase in trkB tyrosine phosphorylation, driven by a 3-fold rise in exon III BDNF mRNA and a 2-fold rise in trkB mRNA. Binding studies in the basal forebrain report a dissociation constant of roughly 2.4 nM. In cerebral-ischaemia models Semax reshapes broad gene programmes, and in an early human study intranasal dosing improved attention and short-term memory in healthy volunteers. These are laboratory and early clinical findings that describe how the compound is researched, not any approved human use.

Side Effects

Most of what is known about Semax tolerability comes from Russian clinical use, where it is marketed intranasally and has been given for stroke, cognitive and optic-nerve indications for several decades. Those reports generally describe good tolerability with few adverse effects, but the independent human safety record is thin: trials outside Russia are limited, structured long-term adverse-event data is largely absent, and Semax holds no FDA or EMA approval. The effects listed below are those noted in the available literature, not a complete or independently confirmed safety profile.

On the whole, Russian clinical experience points to a mild adverse-effect profile dominated by minor local and metabolic findings, with no signal for sedation, dependence, or serious harm at the doses studied. That said, the evidence rests heavily on one national research tradition, lacks independent Western replication and long-term follow-up, and should be read as suggestive rather than a demonstration that Semax is proven safe.

At a glance

The sequence is Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), molecular formula C37H51N9O10S. Molecular weight and CAS are confirmed against PubChem.

Dosing

Semax has never been approved by the FDA or EMA, so there is no Western reference dose. The figures below come from Russian clinical use and published studies, where it is given intranasally as a 0.1% or a 1% solution. Lower amounts appear in cognitive and mild neurological contexts, while acute ischemic stroke protocols use much larger daily amounts. Independent, non-Russian dosing data are limited, and several source doses are reported per kilogram of body weight rather than as fixed amounts.

Reported doses vary widely by indication, from microgram-per-kilogram amounts for cognitive and experimental work up to 12 to 18 mg per day in acute stroke care. Because most of this evidence comes from Russian clinical practice and studies, independent confirmation is limited. This information is educational and reflects doses used in research and clinical reports, not instructions for use; these materials are for laboratory research use only.

Preparing it

Semax is supplied as a lyophilised powder and is reconstituted with bacteriostatic or sterile water before use in the laboratory. See the reconstitution guide for step-by-step handling, and the concentration guide for working out the amount of solvent needed to reach a target concentration. Store the sealed vial cold and keep reconstituted solution refrigerated at 2-8 C.

Where to go next

Last updated on July 3, 2026