Section 01
What it's used for
Cortex effects seen only in rats
Cortagen was designed from amino acids in the cattle-brain drug Cortexin. In lab-grown rat brain tissue, it boosted cortex growth. In rats with reduced brain blood flow, it sped behavior recovery. No human cognitive-decline trial was found.
▸Clinical wording
Cortagen (Ala-Glu-Asp-Pro) was synthesised from the amino acid composition of the cattle-brain preparation Cortexin, and its claimed tissue selectivity rests on organotypic culture experiments: in rat explant cultures cortagen stimulated growth of cerebral cortex tissue specifically, consistent with the general "tissue-specific" pattern the authors report for this peptide family. The only functional cognitive-type evidence is behavioural work in rats — in a chronic brain ischemia model cortagen accelerated recovery of disturbed individual behaviour and limited excessive lipid peroxidation in brain tissue. No trial of cortagen in people with cognitive decline is indexed in PubMed, and the one large-scale molecular screen of the peptide (a cDNA microarray of 15,247 transcripts after five daily injections) was performed in mouse heart, not brain. The entire evidence base is preclinical and originates from one Russian research network.
No human stroke trials exist
There are no published human stroke trials of cortagen; evidence is from rats with reduced brain blood flow, where it sped behavior recovery and limited oxidative brain damage. Human stroke data belong to a related drug, Cortexin.
▸Clinical wording
There are no human stroke trials of cortagen in the published literature — this direction rests entirely on rodent cerebral ischemia experiments from one military-medical pharmacology department in St. Petersburg. In rats with chronic brain ischemia, cortagen and cortexin both accelerated recovery of disturbed behaviour in animals of high and low hypoxia resistance and prevented excessive lipid peroxidation with loss of antioxidant activity in brain tissue. A follow-up study in which cortagen was among the neurospecific peptide preparations tested reported reduced neurological deficit and antioxidant action during chronic ischemic brain damage in the early and late phases of ischemic preconditioning. These are small animal experiments without independent replication, and they should not be read as evidence of benefit after stroke in humans; the human stroke data in this peptide family belong to Cortexin, a different preparation.
Studied in blood cells, not brains
This work was done on blood cells, not neurons. In immune cells from people aged 75-88, cortagen reopened age-silenced genes; a 2023 study repeated this finding. No study tested cortagen in Alzheimer's, Parkinson's or other brain diseases.
▸Clinical wording
The aging-related work on cortagen was done on blood cells, not neurons. In lymphocyte cultures from people aged 75–88 years, cortagen — together with the related peptides Vilon, Epithalon, Livagen and Prostamax — activated ribosomal genes and decondensed the densely packed chromatin that accumulates with age, releasing genes repressed by age-related chromatin condensation; a 2023 replication from a Georgian genetics group reported the same selective deheterochromatinisation for cortagen and three sister peptides. This is a cell-level epigenetic observation in cultured lymphocytes with no cognitive, imaging or clinical endpoint attached, and separate organotypic experiments only showed that cortagen affects explant growth from brains of rats of different ages. No study has tested cortagen in a model of Alzheimer's disease, Parkinson's disease or any other defined neurodegenerative condition, nor in patients.
Best-studied use: rat nerve repair
In rats with a cut, repaired sciatic nerve, 10 days of cortagen sped nerve-fiber regrowth by 27% and signal speed by 40%, unreplicated outside one lab. A separate paper claims a strong human effect, but no matching trial exists.
▸Clinical wording
This is the best-documented cortagen direction and it is missing from the usual summaries. In rats whose sciatic nerve had been transected and sutured, intramuscular cortagen at 10 µg/kg for 10 days increased the growth rate of regenerating nerve fibres by 27% and their conduction velocity by 40%; a follow-up report from the same Pavlov Institute laboratory described a delayed improvement in injured-nerve function. Both are small single-group animal experiments that have not been replicated outside that laboratory. A Khavinson-group paper asserts in passing that in humans cortagen "demonstrated a pronounced therapeutic effect upon the structural and functional posttraumatic recovery of peripheral nerve tissue", but no corresponding human trial appears in PubMed, so that assertion is unsupported by any retrievable primary report.
Section 02
Mechanism of Action
What this molecule actually is
- Cortagen is a laboratory-made chain of four amino acids, alanine-glutamate-aspartate-proline (AEDP).
- Its sequence was designed from the amino-acid make-up of Cortexin, a brain-cortex extract.
- It is a synthetic copy derived from a complex extract, not a natural signalling peptide of the body.
- It differs from Epithalon by one end residue, and that single swap repeatedly changes the biological outcome.
▸Clinical wording
Peptide identity and origin
Cortagen is the tetrapeptide AEDP (Ala-Glu-Asp-Pro). It was produced by directed synthesis based on amino-acid analysis of Cortexin, the natural brain-cortex polypeptide preparation, so it is a synthetic single-sequence analogue derived from a complex extract rather than an isolated endogenous signalling peptide. It differs from Epithalon (AEDG) only in the C-terminal residue, and that single substitution repeatedly produces different biological outcomes, which argues against a generic "short peptide" effect and for sequence-specific action.
Each peptide favours its own tissue
- In dishes of rat tissue pieces, Cortagen increased outgrowth from brain cortex.
- Related peptides instead favoured the tissue whose extract had supplied their amino-acid recipe.
- The same selectivity was reproduced in tissue taken from rats of different ages.
- The readout is growth area in culture, not a defined receptor interaction.
▸Clinical wording
Tissue-specific stimulation of explant growth
In organotypic culture of rat tissues, Cortagen stimulated outgrowth of explants from brain cortex, while Epithalon, Livagen and Vilon preferentially stimulated explants from subcortical structures, liver and thymus respectively. The reported rule is that each peptide stimulates growth of the tissue whose cytomedin (peptide complex) supplied the amino-acid composition used for its synthesis. This tissue selectivity was reproduced across explants from rats of different ages. The effect is a growth-area readout in explant culture, not a defined receptor interaction.
A broad but indirect gene survey
- Mice given Cortagen for five days had heart tissue screened across 15,247 gene probes.
- Activity changed for 234 probes, about 1.5 percent, corresponding to roughly 110 known genes.
- Some changes were shared with related peptides and some were specific to Cortagen.
- This broadest unbiased survey was carried out in heart tissue rather than in brain.
▸Clinical wording
Genome-wide transcriptional response in vivo
A cDNA microarray covering 15,247 transcripts was run on heart tissue of female CBA mice given Cortagen for five consecutive days. Expression changed significantly for 234 clones — 1.53 percent of the array — corresponding to about 110 known genes across several functional categories, with regulation spanning +5.42 to -2.86 fold. Comparison against Vilon, Epitalon and melatonin in the same system revealed both shared and Cortagen-specific changes. This remains the broadest unbiased description of a Cortagen transcriptional footprint, and it was obtained in heart rather than brain.
Loosening tightly packed genetic material
- In white blood cells from donors aged 75 to 88, Cortagen switched on ribosome-making genes.
- It loosened densely packed genetic fibres, releasing genes that age-related packing had silenced.
- Unlike two sibling peptides, it left one structural packed region of chromosome 1 untouched.
- A separate laboratory in Tbilisi reproduced this selective, region-specific loosening using different methods.
▸Clinical wording
Chromatin decondensation in senescent human lymphocytes
In cultured lymphocytes from subjects aged 75-88, Cortagen — together with Vilon, Epithalon, Livagen and Prostamax — activated ribosomal genes at the nucleolar organiser regions, decondensed densely packed chromatin fibrils, and released genes repressed by age-related condensation of euchromatin (deheterochromatinisation of facultative chromatin). Cortagen differed from Epithalon and Livagen in that it did not decondense the pericentromeric structural heterochromatin of chromosome 1. Independent work in Tbilisi using differential scanning calorimetry, NOR activity and sister-chromatid exchange reproduced this selective, region-specific chromatin remodelling for AEDP.
Mixed effects on immune signalling
- In mouse spleen cells Cortagen switched on an immune messenger gene (interleukin-2) without any trigger.
- The response was weaker than for two sibling peptides and depended on concentration and exposure time.
- In rat brain sections it also altered that gene in the hypothalamus, direction varying with timing and route.
- It produced no effect on mouse thymus cell growth and only weak stimulation of one membrane enzyme.
▸Clinical wording
Cytokine gene expression and immune readouts
Cortagen activated interleukin-2 mRNA synthesis in mouse splenocytes in vitro without a specific inducer, though less strongly than Vilon or Epithalon, with the response depending on concentration and exposure time. In situ hybridisation on rat brain sections showed that Cortagen also modulated IL-2 gene expression in hypothalamic structures in vivo, with the direction depending on timing and route of administration. Negative results bound this: Cortagen produced no comitogenic effect on mouse thymocyte proliferation and only weak stimulation of membrane sphingomyelinase compared with Vilon.
Nerve repair and oxidative damage in rats
- After a cut rat sciatic nerve was stitched, ten days of Cortagen sped fibre growth by 27 percent.
- Conduction speed along those fibres rose 40 percent, and a follow-up described a delayed component.
- In rats it lowered markers of fat and protein oxidative damage in blood and brain cortex.
- In chronic brain blood-shortage models it preserved tissue antioxidant activity and speeded behavioural recovery.
▸Clinical wording
Peripheral nerve regeneration and redox effects
After transection and suturing of the rat sciatic nerve, a ten-day intramuscular course of Cortagen increased the growth rate of regenerating fibres by 27 percent and their conduction velocity by 40 percent; a follow-up study described a delayed component to this functional restoration. In rats, Cortagen lowered lipid peroxidation products and oxidative modification of proteins in serum and cerebral cortex. In chronic brain ischaemia models, Cortexin and Cortagen both prevented excessive activation of lipid peroxidation and the fall in tissue antioxidant activity, and accelerated recovery of disturbed individual behaviour.
How thin the evidence really is
- Nearly all studies are in rodents or isolated tissue, published between 2000 and 2011.
- Almost all came from the originating group, in Russian-language or Russian-affiliated journals.
- Only the Georgian chromatin work replicated anything independently, and no controlled human trial exists.
- Several studies report Cortagen doing nothing where sibling peptides corrected the same changes.
▸Clinical wording
Evidence base
The Cortagen literature is small, almost entirely rodent or ex vivo, published between 2000 and 2011 largely by the originating group in Russian-language or Russian-affiliated journals, and has not been independently replicated outside that circle apart from the Georgian chromatin work. There is no controlled human trial. Several studies report Cortagen doing nothing where sibling peptides acted — for example it failed to correct erythrocyte, immune or haemostasis changes in neonatally hypophysectomised chickens where Epithalon fully corrected them. Any mechanistic account should be read as preliminary.
Section 03
Biological Pathways
- Tissue-selective explant stimulationIn organotypic rat tissue culture, Cortagen stimulated outgrowth of brain cortex explants, consistent with the rule that each cytomedin peptide favors the tissue supplying its amino-acid composition.
- Genome-wide transcriptional responseA cDNA microarray of 15,247 transcripts in mouse heart found change for 234 clones after five days of Cortagen, about 110 genes regulated from plus 5.42 to minus 2.86 fold, versus Vilon, Epitalon and melatonin.
- Chromatin decondensation in aged cellsIn lymphocytes from subjects aged 75 to 88, Cortagen activated ribosomal genes at nucleolar organiser regions and decondensed age-condensed euchromatin, but unlike Epithalon it spared chromosome 1 heterochromatin.
- IL-2 expression and nerve regenerationCortagen activated IL-2 mRNA in mouse splenocytes and modulated hypothalamic IL-2 expression in rats; after sciatic nerve transection it raised fibre growth rate 27 percent and conduction velocity 40 percent.
Section 04
Dosage Information
Ala-Glu-Asp-Pro| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Intramuscular — only human dosing | Head-injury aftermath, 15 patients, in the patent | 1 µg a day for 10 days — about 0.011–0.014 µg/kg at 70–90 kg. The patent itself states 0.01–100 µg/kg a day for 10–40 days. | Fifteen patients added to standard care, unblinded, outcomes told in words with no scale or statistics. Never published outside the patent. |
| Intramuscular / into the abdomen | Cut nerve in rats; nerve injury and learning in mice | 10 µg/kg into muscle for 10 days in rats; 10 µg/kg into the abdomen for 8 days in mice; 5 µg/kg once before a mouse learning test | A cut nerve in rodents, not memory in an ageing adult. Nobody converted the animal dose to a human one, so µg/kg cannot just be multiplied by weight. |
| Subcutaneous — self-administration | Circulating practice built around the 20 mg vial | 0.5–2 mg a day — roughly 6–29 µg/kg for a 70–90 kg adult — in courses of 10–20 days, two or three times a year | Five hundred to two thousand times the 1 µg ever given to a person, by a route the patent never used. Its source is vial size and vendor charts. |
| Intramuscular — safety tests in rodents | The safety package inside the developer's patent | Single doses of 1–5 mg/kg in mice; 1 µg/kg, 0.3 mg/kg and 3 mg/kg daily for 90 days in rats, with no deaths or toxic signs reported | Unpublished animal data from the party that patented the peptide, never repeated by anyone else. It says nothing about human safety at milligram doses. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
No data for this section yet.
Section 07
Side Effects & Precautions
No toxicology study, dose-ranging trial, or registered clinical study of Cortagen has been found. What is published are behavioural findings in rats, an off-target signal in mice, and one mix-up worth flagging.
Rat behaviour: suppressed, then more aggressive
In rats, Cortagen given systemically mildly suppressed exploratory and emotional behaviour and moderately raised aggressiveness. Given straight into the brain ventricle instead, the effect reversed into activation and reduced anxiety; the authors report no clear explanation for this reversal.
Off-target signal in the mouse heart
A five-day course of Cortagen in mice altered expression of over a hundred heart genes, an organ the peptide is not marketed to act on. No histology or heart-function testing was done. Like most Cortagen data, it comes from the peptide's originating group; independent reproduction does not exist.
No published human study exists
A claim that Cortagen had a pronounced effect on nerve recovery, plus unspecified cardiovascular and cerebrovascular effects, in humans appears in the developers' paper with no citation or adverse-event detail. PubMed indexes no clinical study of Cortagen; no ClinicalTrials.gov record exists.
Not a medicine anywhere
An independent Russian pharmacology review describes Cortagen as only a prospective preparation, unlike Cortexin and Cerebrolysin, which are already used in clinical practice. The developers' own catalogue likewise does not list Cortagen as a medicinal product.
Not the same substance as Cortexin
Cortagen is a synthetic tetrapeptide designed from the amino-acid analysis of Cortexin, a registered bovine-brain complex with its own clinical safety record. Cortexin's tolerability data do not transfer to Cortagen, and no source examined attributes an adverse-effect profile to Cortagen itself.
Section 08
Regulatory Status
In Russia it is sold as a dietary supplement under bioregulator rules, not as a registered pharmaceutical, and outside Russia it circulates only as an unapproved research chemical.
FDA / United States
Not approved; sold as a research chemical
Cortagen has no FDA marketing approval and no drug application on record. Vendors sell it strictly as a «research use only» peptide, stating explicitly that it is not intended for human use.
EMA / European Union
No marketing authorisation exists
There is no EU authorisation for Cortagen as a medicine or as a food supplement. It has not been assessed by the EMA or by any national EU regulator.
Russia
Sold as a supplement, not a registered drug
Developed at the St. Petersburg Institute of Bioregulation and Gerontology as a synthetic peptide successor to Cortexin, Cortagen is marketed in Russia as a capsule dietary supplement (БАД). Unlike Cortexin, it carries no state pharmaceutical registration number.
Clinical evidence
No published human trials support its use
Evidence is limited to animal experiments and work from the developer's own institute; no Western randomised human trial has been published, and independent replication is essentially absent.
WADA
Not named on the list; S0 applies by definition
Cortagen is not listed by name on the WADA Prohibited List, but as a pharmacological substance with no approval anywhere for human therapeutic use, it meets the definition of category S0 (Non-Approved Substances).
A dietary-supplement listing in one country is not a drug approval, and it does not carry over to other jurisdictions. Regulatory status differs between countries and changes over time — check current official sources before relying on any of this.
Section 09
Research Studies
- [1]Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarrayAnisimov SV, Khavinson VKh, Anisimov VN. · Neuro Endocrinology Letters · 2004
- [2]Tissue-specific effects of peptidesKhavinson VK. · Bulletin of Experimental Biology and Medicine · 2001
- [3]Effects of short peptides on lymphocyte chromatin in senile subjectsKhavinson VKh, Lezhava TA, Malinin VV. · Bulletin of Experimental Biology and Medicine · 2004
- [4]Epigenetic modification under the influence of peptide bioregulators on the "old" chromatinLezhava T, Jokhadze T, Monaselidze J, Buadze T, Gaiozishvili M, Sigua T, Khujadze I, Gogidze K, Mikaia N, Chigvinadze N. · Georgian Medical News · 2023
- [5]In vitro effect of short peptides on expression of interleukin-2 gene in splenocytesKazakova TB, Barabanova SV, Khavinson VKh, Glushikhina MS, Parkhomenko EP, Malinin VV, Korneva EA. · Bulletin of Experimental Biology and Medicine · 2002
- [6]Synthesis of IL-2 mRNA in cells of rat hypothalamic structures after injection of short peptidesKazakova TB, Barabanova SV, Novikova NS, Glushikhina MS, Khavinson VKh, Malinin VV, Korneva EA. · Bulletin of Experimental Biology and Medicine · 2005
- [7]Effects of short peptides on thymocyte blast transformation and signal transduction along the sphingomyelin pathwayKhavinson VKh, Rybakina EG, Malinin VV, Pivanovich IY, Shanin SN, Korneva EA. · Bulletin of Experimental Biology and Medicine · 2002
- [8]Effect of tetrapeptide cortagen on regeneration of sciatic nerveTurchaninova LN, Kolosova LI, Malinin VV, Moiseeva AB, Nozdrachev AD, Khavinson VK. · Bulletin of Experimental Biology and Medicine · 2000
- [9]The delayed effect of cortagen on the restoration of injured nerve functionKolosova LI, Moiseeva AB, Turchaninova LN, Malinin VV, Polyakov EL, Nozdrachev AD, Khavinson VKh. · Doklady Biological Sciences · 2002
- [10]Effects of bioactive tetrapeptides on free-radical processesKozina LS. · Bulletin of Experimental Biology and Medicine · 2007
- [11]Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia (in Russian)Zarubina IV, Shabanov PD. · Eksperimental'naia i Klinicheskaia Farmakologiia · 2011
- [12]Effects of epithalon and cortagene on immunity and hemostasis in neonatally hypophysectomized chicken and old birds (in Russian)Kuznik BI, Pateiuk AV, Baranchugova LM, Rusaeva NS. · Advances in Gerontology · 2008
Section 10
Frequently Asked Questions
Nearly the entire evidence base is preclinical — rat cerebral-ischemia behaviour, sciatic-nerve regeneration in rats, and chromatin changes in cultured lymphocytes from elderly donors, all from one Russian research network with no independent replication outside it. The only reported human use is an unblinded 15-patient case series added to standard head-injury care, described only in the developer's patent and never published in a peer-reviewed journal. No controlled human trial of cortagen exists.
The one human dose on record — 1 µg a day for 10 days, from that unpublished 15-patient patent case series — sits 500 to 2,000 times below the 0.5 to 2 mg a day that circulates in self-administration practice. Rodent studies used roughly 10 µg/kg, and nobody has published a conversion from that animal dose to a human one, so the milligram doses in circulation trace back to vial size and vendor charts, not a dose-finding study.
The material reviewed lists side effects as "minimal reported," which reflects an absence of systematic monitoring rather than a confirmed clean safety record — the one human case series that exists did not track adverse events on any formal scale. Unpublished rodent toxicity data in the developer's own patent reported no deaths or toxic signs at doses far above the human dose, but that has never been independently repeated.
No FDA, EMA or other major-regulator approval record for cortagen appears in the material reviewed; it is categorised here as an experimental compound with essentially no clinical dossier behind it — unlike its relative Cortexin, which is registered for medical use in Russia.
Cortagen is a synthetic four-amino-acid peptide (Ala-Glu-Asp-Pro) designed by analysing the amino-acid composition of Cortexin, a natural bovine brain-cortex extract — so it's a single defined sequence derived from that complex mixture, not the same substance. Cortexin has randomised, placebo-controlled human trials in stroke, even though a 2023 Cochrane review found little mortality benefit; cortagen has no equivalent human evidence at all, only the rodent and cell-culture work described above.
No storage or stability information for cortagen was found in the material reviewed — unlike related peptides such as Cortexin, no shelf life, temperature range or reconstitution guidance is documented here.
In rat explant cultures cortagen selectively stimulated growth of cerebral cortex tissue, and in aged human lymphocytes (75-88 years old) it activated ribosomal genes and loosened age-related chromatin condensation alongside several sister peptides. A broader genome-wide screen found it altered expression of roughly 110 genes in mouse heart tissue, not brain. None of this establishes a defined receptor or pathway, and none has been tested against a cognitive or clinical endpoint in humans.