Semax
Synthetic ACTH(4–10) analogue heptapeptide · Research-grade reference material
Identity
- Molecular formula
- C37H51N9O10S
- Molecular weight
- 813.93 g/mol
- CAS number
- 80714-61-0
Research Background
Semax is a synthetic fragment of adrenocorticotropic hormone (ACTH), isolating the 4-7 segment responsible for neurotrophic activity while excluding the hormonal effects ACTH has on the adrenal glands. A Pro-Gly-Pro tripeptide extension was added to resist enzymatic degradation.
Developed in 1982 by Nikolay Myasoedov and Igor Ashmarin at the Institute of Molecular Genetics of the Russian Academy of Sciences. Semax is formally approved in Russia in two formulations and has been on Russia’s List of Vital and Essential Drugs since 2011. It is not approved by the FDA, EMA, or any Western regulator.
Lab-tested research material
Mechanism
Intranasal Semax raises BDNF and trkB receptor expression in the rat hippocampus (Dolotov et al.), supporting neuron survival and synaptic plasticity. In cerebral ischemia models, Semax has been shown to regulate the expression of genes controlling immune cell activity, part of its studied neuroprotective effect following brain injury (Dmitrieva et al.).
Semax has been investigated since the 1980s–1990s, predominantly by Russian research groups, in neuroprotection, cerebral ischemia and cognition models. The C-terminal Pro-Gly-Pro extension distinguishes it from the parent ACTH fragment by conferring greater metabolic stability. Findings below derive from animal and cell-culture systems. They are not established effects in humans.
BDNF / TrkB modulation. Dolotov et al. (2006) reported increased BDNF protein and TrkB phosphorylation, with elevated exon III BDNF and trkB mRNA, in rat hippocampus.
Neurotrophin gene expression. Rapid, gene- and region-specific changes in neurotrophin expression reported in rat brain.
Ischemia models. Activation of neurotrophic factor expression and modulation of VEGF-A mRNA in frontal cortex and hippocampus in cerebral ischemia models; reduced infarct volume reported.
Monoaminergic modulation. Reported effects on dopaminergic, serotonergic and cholinergic systems.
Melanocortin receptor interaction. Described in the literature as an MC4 receptor antagonist while lacking ACTH corticotropic activity.
Proposed pathways investigated in preclinical (animal / in-vitro) models. Schematic only; not a claim of established human effect.
State of the Evidence
The research base is large and decades-deep but concentrated almost entirely in Russian-language literature and Russian institutions. Independent, large-scale trials from outside that system remain limited. A widely circulated claim linking Semax to ADHD treatment or stimulant-like cognitive enhancement traces to a single 2006 hypothesis paper, not a completed clinical trial, worth reading as exactly what it is rather than as settled evidence.
1. Animal — “Semax, an Analog of ACTH(4-10) with Cognitive Effects, Regulates BDNF and trkB Expression in the Rat Hippocampus,” Brain Research, 2006. PMID 16996037
2. Animal — “Semax, an Analog of ACTH(4-7), Regulates Expression of Immune Response Genes During Ischemic Brain Injury in Rats,” Molecular Genetics and Genomics, 2017. DOI 10.1007/s00438-017-1297-1
3. Hypothesis Paper (not supportive evidence) — “Semax…Is a Potential Agent for the Treatment of Attention-Deficit Hyperactivity Disorder and Rett Syndrome,” Medical Hypotheses, 2006. Proposes Semax as an ADHD candidate based on animal data; no completed human trial has followed.
What the Literature Supports — and What It Doesn’t
Semax occupies an unusual position: it is an approved medicine in Russia, yet has not been approved by the FDA or EMA, and large-scale randomized controlled trial data available in Western indexed literature remains limited. Much of the primary research is Russian-published.
Evidence at a glance
The BDNF/TrkB mechanism is supported by specific, quantified preclinical findings (rat hippocampus), not merely asserted.
A large share of the literature originates from a single national research tradition, with less independent Western replication than the volume of publications alone might suggest.
Regulatory divergence is itself informative: approval in one jurisdiction alongside non-approval in the US and EU indicates the evidence base has not met FDA/EMA standards.
Reported human use in stroke and cognitive-disorder contexts should not be read as establishing efficacy under Western regulatory evidentiary standards.
Appropriate characterization: a neuroactive peptide with a well-described preclinical neurotrophic mechanism and a national regulatory approval, but without the independent large-scale controlled human evidence required for FDA or EMA authorization.
Regulatory & status notes
Selected references
- 1. 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(1):54–60. PMID 16996037.
- 2. Dolotov OV, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of BDNF protein in rat basal forebrain. J Neurochem. 2006;97 Suppl 1:82–86.
- 3. Adan RA, et al. Identification of antagonists for melanocortin MC3, MC4 and MC5 receptors. Eur J Pharmacol. 1994;269:331–7.
- 4. Semax peptide targets Oprm1 to promote deubiquitination and functional recovery after spinal cord injury (murine model).
Safety Information
Research-use compound with limited human data. Evidence strength varies — see the Evidence section above.
No established clinical contraindications. This is an investigational compound with limited human data and has not been evaluated by the FDA for safety in this context. Consult a qualified clinician. For research and educational purposes only, not for human or veterinary use.
Related Compounds
For research and educational purposes only. Not for human or veterinary use.