Research Guide · Semax

What is Semax?

A synthetic ACTH(4-10) heptapeptide analogue developed in Russia for neuroprotection, BDNF/NGF upregulation, and cognitive enhancement research.

Updated September 2026 Research Use Only 11 min read

What is Semax

A neuropeptide analogue of ACTH(4-10) developed at the Russian Academy of Sciences for nootropic and neuroprotective research.

Structure & Chemistry

Semax is a synthetic heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP). It comprises the ACTH(4-10) fragment (MEHFP) extended C-terminally with -Pro-Gly-Pro to confer enzymatic stability. CAS 80714-61-0; MW 813.91 Da.

Origins & Development

Developed in the 1980s at the Institute of Molecular Genetics, Russian Academy of Sciences (Ashmarin lab). Listed in the Russian Vital and Essential Drugs registry; used clinically in Russia for stroke recovery, cognitive disorders, optic nerve atrophy, and ADHD.

Receptor & Mechanism

Weak melanocortin receptor activity at research doses (no pigmentation). Primary mechanism is upregulation of BDNF, NGF, and other neurotrophic factors with downstream modulation of dopaminergic, serotonergic, and limbic-cortical neurotransmission.

Mechanism of Action

Neurotrophic factor modulation and CNS delivery via the intranasal route.

BDNF & NGF Upregulation

Semax rapidly upregulates brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) gene expression in cortical and limbic regions via TrkB-dependent signalling. The neurotrophic upregulation underlies cognitive-enhancing and neuroprotective research observations (Levitskaya et al.; Andreeva et al.).

Monoaminergic Modulation

Semax modulates dopamine and serotonin pathways in mesolimbic circuits, contributing to attention, motivation, and mood-related research outcomes. Effects are indirect via neurotrophic and synaptic plasticity mechanisms rather than direct receptor agonism.

Melanocortin Receptor Modulation (Low Affinity)

Retains weak melanocortin receptor binding inherited from its ACTH(4-10) origin, but at research-relevant doses does not produce pigmentation or cortisol elevation characteristic of full ACTH or melanocortin agonists.

Intranasal Delivery & CNS Penetration

Signature delivery is intranasal spray, exploiting olfactory and trigeminal pathways for direct nose-to-brain transit. Bioavailability to CNS is approximately 0.1% of nasally administered dose, sufficient for measurable neurotrophic gene expression changes within minutes.

Semax vs Related Neuropeptides

Comparison with Selank, ACTH, and other nootropic compounds.

Compound

Mechanism Class

Research Distinction

Semax

ACTH(4-10) heptapeptide; BDNF/NGF inducer

Cognitive enhancement, neuroprotection in stroke models, ADHD research

Selank

Tuftsin analogue heptapeptide; anxiolytic

Anxiolytic via enkephalinase inhibition; no sedation/dependence; complementary to Semax

ACTH (1-39)

Endogenous corticotropin

Full HPA-axis activation; cortisol release; not a nootropic profile

Cerebrolysin

Porcine brain-derived peptide mixture

Multi-component; broader peptide profile; longer-established Western clinical research

Noopept

Synthetic dipeptide piracetam analogue

NGF/BDNF induction; oral bioavailability; different chemical class

Research Context: Semax and Selank were developed by the same Russian lab using parallel design philosophy (peptide fragment + C-terminal Pro-Gly-Pro stabilisation). Semax targets cognitive enhancement and neuroprotection; Selank targets anxiolysis. They are sometimes combined in research models but address distinct therapeutic areas.

Key Research Applications

Primary research domains for Semax.

Stroke & Neuroprotection Models

The most extensive Russian clinical literature. Semax is studied for ischaemic stroke recovery via BDNF/NGF-mediated neuroprotection, neuroplasticity restoration, and reduced glutamate excitotoxicity (Skvortsova, Gusev, et al.).

Cognitive Enhancement Research

Working memory, attention, and executive function research models. Semax is investigated as a nootropic candidate, with mechanism via neurotrophic factor upregulation distinct from cholinergic agents (donepezil) or NMDA modulators (memantine).

ADHD & Attention Models

Russian clinical trials in paediatric ADHD show attention improvements; research interest centres on its non-stimulant mechanism via BDNF/dopamine modulation, contrasting with methylphenidate or amphetamine pharmacology.

Optic Nerve & Peripheral Nerve Repair

Approved Russian indication includes optic nerve atrophy. Research extends to peripheral nerve regeneration models leveraging Semax’s NGF-induction effects.

Neurodegenerative Disease Models

Animal models of Parkinson’s, Alzheimer’s, and Huntington’s disease investigate Semax’s neurotrophic and antioxidant properties, particularly its potential to slow dopaminergic neuron loss in MPTP models.

Quick Reference Specifications

Key biochemical parameters.

P · 01

Designation

Semax (ACTH(4-10) heptapeptide analogue)

P · 02

Sequence

Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP)

P · 03

CAS Number

80714-61-0

P · 04

Molecular Weight

813.91 Da

P · 05

Molecular Formula

C37H51N9O10S

P · 06

Origin

Institute of Molecular Genetics, Russian Academy of Sciences (Ashmarin lab, 1980s)

P · 07

Mechanism

BDNF/NGF upregulation; weak melanocortin receptor; monoaminergic modulation

P · 08

Route

Intranasal spray (signature); subcutaneous in animal studies

P · 09

CNS Bioavailability

~0.1% of nasal dose reaches CNS

P · 10

Storage

Lyophilised: 2–8°C; reconstituted nasal solution: 2–8°C, stable 2–4 weeks

Reconstitution & Storage

Handling guidance for nasal/research preparation.

Reconstitution

Reconstitute lyophilised Semax with sterile bacteriostatic water or sterile saline. For nasal spray preparation, dissolve to a typical research concentration of 0.1–1 mg/mL. Use sterile syringes; gentle dissolution; avoid shaking.

Nasal Solution Preparation

Transfer reconstituted solution to a sterile metered nasal spray bottle for animal-model intranasal delivery research. Typical research dose ranges (rodent models) are 50–250 µg per dose, applied as nasal drops or atomised spray.

Storage Timeline

Lyophilised vials stable for years at 2–8°C. Reconstituted solutions maintain bioactivity 2–4 weeks at 2–8°C. Protect from light. Avoid freeze-thaw cycles.

Handling Best Practices

Maintain refrigeration; document reconstitution date; aliquot for extended programmes; use fresh sterile dispensers per research subject; discard solutions older than 4 weeks or showing visible degradation.

Key Published Research

Peer-reviewed studies behind Semax’s research profile.

2006

Neurotrophic signalling

Semax increased BDNF and TrkB receptor expression in the rat hippocampus — the basis for its reputation as a BDNF-modulating peptide.¹

2014

Brain ischaemia transcriptome

Genome-wide analysis of a rat focal ischaemia model showed Semax shifted the expression of genes linked to immune and vascular responses.²

2018

Clinical stroke study

A Russian clinical study evaluated Semax in patients at different stages of ischaemic stroke.³

Regulatory & Research Status

Where Semax stands in 2026.

APR 26

FDA Category 2 removal

Semax was one of twelve peptides removed from the US FDA’s Category 2 compounding list. This is not an approval.

JUL 26

Advisory committee vote

The FDA’s Pharmacy Compounding Advisory Committee voted 8–5 (one abstention) to recommend Semax for the 503A bulks list for proposed cerebral ischaemia, migraine and trigeminal neuralgia uses. The vote is non-binding and formal rulemaking would follow.

UK / EU

Approval status

Semax is registered in Russia but is not an approved medicine in the UK, EU or US.

Evidence Quality & Limitations

Most clinical data on Semax appear in Russian-language journals, often from small or open-label studies linked to the developing institutes, and independent replication elsewhere is limited. Mechanistic findings such as BDNF and NGF up-regulation come largely from rodent studies, and figures such as the nasal-to-CNS bioavailability quoted above rest on a small number of animal experiments.

References

Dolotov OV, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117:54–60. PubMed
Medvedeva EV, et al. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics. 2014;15:228. PubMed
Gusev EI, et al. The efficacy of semax in the treatment of patients at different stages of ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118:61–8. PubMed

⚠ Research Use Only. The compounds discussed in this guide are intended strictly for in-vitro laboratory research. Not for human consumption, therapeutic use, or veterinary application. Researchers must comply with all applicable local regulations.