Peptides: Semax Overview — ACTH 4-7 Pro-Gly-Pro Analogue
Semax (ACTH 4-7 Pro-Gly-Pro) increases BDNF mRNA expression in rat hippocampus within 15–20 minutes at 50–200mcg/kg doses. Russian clinical data supports nootropic use. Grade B (Russian).
| Measure | Value | Unit | Notes |
|---|---|---|---|
| Evidence Grade | B | grade | Russian clinical trials support nootropic/neuroprotective use; most data in Russian-language journals; Grade C by Western peer-review standards |
| Peptide Sequence | Met-Glu-His-Phe-Pro-Gly-Pro | heptapeptide | ACTH(4-7) = Met-Glu-His-Phe; Pro-Gly-Pro extension added for metabolic stability and CNS penetration |
| Standard Intranasal Dose | 300–600 | mcg/day | Administered in 1–3 divided doses via nasal spray; standard Russian clinical protocol |
| BDNF Onset | 15–20 | minutes | BDNF mRNA upregulation detectable in rat hippocampus within 15–20 min (PMID 18457799); faster than most nootropics |
| Origin | 1980s | development decade | Developed at Institute of Molecular Genetics, Moscow; licensed in Russia for ischemic stroke and cognitive impairment |
| Primary Route | Intranasal | route | Nasal mucosa allows direct CNS access; subcutaneous also used in research; oral bioavailability negligible |
| ACTH Fragment Source | 4–7 | ACTH residue positions | ACTH(4-7) = adrenocorticotropin fragment; cognitive-promoting without steroidogenic or cortisol-releasing activity of full ACTH |
Semax: Russian Neurotrophin Peptide
Semax is a 7 amino acid synthetic peptide based on the adrenocorticotropic hormone fragment ACTH(4-7), extended by the tripeptide Pro-Gly-Pro for enhanced metabolic stability. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow during the 1980s and 1990s, and has been licensed in Russia as a prescription drug for ischemic stroke treatment and cognitive impairment for over two decades.
The full sequence is Met-Glu-His-Phe-Pro-Gly-Pro. The ACTH(4-7) core (Met-Glu-His-Phe) carries the neuroactive properties, while Pro-Gly-Pro provides resistance to peptidase degradation and extends activity duration after intranasal administration.
Pharmacological Profile
| Effect | Proposed Mechanism | Evidence Level | Notes |
|---|---|---|---|
| BDNF upregulation | MC4R/CREB pathway → BDNF transcription | B (Russian); C (Western) | Onset 15–20 min in rodents (PMID 18457799) |
| Cognitive enhancement | BDNF + cholinergic system modulation | B (Russian clinical) | Licensed for TIA/stroke cognitive recovery in Russia |
| Neuroprotection | Anti-excitotoxic; oxidative stress reduction | C | Animal models; ischemia studies |
| Attention/focus | Dopaminergic modulation (proposed) | C | Anecdotal human reports; limited controlled data |
| Anxiolytic (mild) | Serotonin modulation (secondary) | D | Weak; selank is preferred for anxiety |
| Pro-Gly-Pro fragment activity | Separate receptor activity; independent neuroprotection | C | PMID 24307957: C-terminal fragment has independent effects |
Dosing Reference
Standard Russian clinical protocol for intranasal Semax:
| Parameter | Value | Notes |
|---|---|---|
| Concentration | 0.1% or 1% nasal solution | 0.1% = 1mg/mL (100mcg/drop); 1% = 10mg/mL (1mg/drop) |
| Standard dose | 300–600mcg/day | 1–2 drops per nostril × 2–3 times daily |
| Research dose range | 250–1000mcg/day | Higher end for neuroprotective/post-stroke context |
| Route | Intranasal (primary) | Subcutaneous used in research; oral ineffective |
| Cycle duration | 10–14 days (Russian clinical) | Followed by break; long-term cycling not well-studied |
| Onset (subjective) | 20–60 minutes | Cognitive activation effect; BDNF onset 15–20 min (preclinical) |
Semax vs Selank at a Glance
| Feature | Semax | Selank |
|---|---|---|
| Primary effect | Cognitive stimulation, nootropic | Anxiolytic, mood stabilization |
| Subjective character | Activating, focused | Calming, anti-anxiety |
| Mechanism | BDNF upregulation, MC4R | GABA-A modulation |
| Best use case | Focus, cognitive work, post-stroke recovery | Anxiety, stress, baseline mood |
| Origin | ACTH(4-7) + Pro-Gly-Pro | Tuftsin analogue |
| Approved in Russia | Yes (stroke/TIA) | Yes (anxiety/nootropic) |
Legal and Regulatory Status
| Jurisdiction | Status | Notes |
|---|---|---|
| USA | Research chemical | Unscheduled; no FDA approval; legal to purchase for research |
| UK | Not scheduled | No Medicines Act restriction; legal to possess |
| Australia | Not TGA-listed | Import for personal use in gray area; no approved product |
| Canada | Gray market | No DIN; Health Canada no approved product |
| EU | Not EMA-approved | Russia: licensed prescription for stroke/TIA; some Eastern EU import available |
Evidence Grade Callout
Grade B — Semax has controlled clinical trial data from Russian institutions supporting its use in stroke recovery and cognitive impairment. It is a licensed prescription drug in Russia. However, the majority of this data is published in Russian-language journals not indexed in PubMed or peer-reviewed by Western standards. Western users should treat Semax as Grade C pending independent replication. The rodent BDNF data (PMID 18457799, PMID 24307957) is well-characterized and provides a plausible mechanistic foundation.
Legal Disclaimer
Semax is not approved by the FDA, EMA, TGA, or Health Canada. Outside Russia and select Eastern European jurisdictions, it is a research chemical. Administration to humans outside approved clinical contexts or licensed medical practice is unsupported by Western regulatory frameworks. This page is for educational purposes and does not constitute medical advice.
Related Pages
Sources
- Agapova TY et al. Effects of Semax on the BDNF system in rat brain. Bull Exp Biol Med. 2007;144(5):636-40. PMID 18457799
- Mironov AN et al. Cognitive effects of Semax in patients after ischemic stroke. Zhurnal Nevrologii. 2003 [Russian]. Referenced in Akhapkina VI 2002 review.
- Kolomin T et al. Comparative analysis of neuroprotective and neurotrophic effects of Semax and its C-terminal fragment Pro-Gly-Pro. Neural Plast. 2013;2013:352976. PMID 24307957
Frequently Asked Questions
What is the difference between Semax and ACTH?
Semax is derived from ACTH (adrenocorticotropic hormone) positions 4 through 7, specifically the tetrapeptide Met-Glu-His-Phe, with a Pro-Gly-Pro tripeptide extension added to improve stability. Full ACTH activates the adrenal cortex to release cortisol — an effect that would be undesirable and stress-inducing if chronically activated. The ACTH(4-7) fragment has no steroidogenic activity; it retains only the neurotrophic and cognitive-enhancing properties attributed to the melanocortin receptor interactions of this region, without hormonal consequences.
How does Semax increase BDNF?
Semax appears to rapidly upregulate BDNF (brain-derived neurotrophic factor) mRNA expression in hippocampal and cortical neurons. The mechanism involves activation of melanocortin receptors (MC1R, MC4R) in CNS tissue, which upregulate BDNF transcription via cAMP/CREB signaling pathways. This effect is measurable within 15–20 minutes in rodent models (PMID 18457799). BDNF promotes synaptic plasticity, neurogenesis, and neuroprotection — making it the primary proposed mechanism for Semax's cognitive and neuroprotective effects.
Is Semax approved anywhere?
Semax is approved in Russia for the treatment of ischemic stroke and transient ischemic attack (TIA), and is used clinically as a cognitive enhancer in Russian neurological practice. It is not approved by the FDA, EMA, TGA, or Health Canada. Outside Russia and some Eastern European countries, Semax is classified as a research chemical with no regulatory approval for human use. Sourcing is through gray-market research chemical suppliers.
How does Semax compare to Selank?
Semax and Selank are both Russian-developed intranasal peptides from the Institute of Molecular Genetics, but with distinct pharmacological profiles. Semax is primarily stimulating and cognitive-enhancing — described as activating and pro-BDNF. Selank is primarily anxiolytic and calming — targeting GABA-A receptor modulation. Semax is more appropriate for focus and cognitive work; Selank for anxiety and baseline mood regulation. They are sometimes used together for these complementary effects.