Section 01
What it's used for
Widely used in Russia, weak evidence
Cortexin is common in Russian child neurology, but most studies are open-label and uncontrolled. In 127 premature infants with birth nerve damage, 40.7% on cortexin plus rehab reached normal development by age 1, vs. 18.2% with rehab alone.
▸Clinical wording
Cortexin is used widely in Russian paediatric neurology, and the supporting studies are numerous but almost all open-label, single-country and without placebo control. In 127 infants born very or extremely preterm with perinatal pyramidal tract damage, normal neurodevelopment on the INFANIB scale at 12 months corrected age was reached by 40.7% of the 59 who received non-drug rehabilitation plus cortexin during the first year versus 18.2% of the 22 given rehabilitation alone (p<0.05); allocation was not randomised. Other reports cover 266 children with delayed speech development treated with cortexin monotherapy, 146 infants aged 20 days to 6 months with perinatal CNS damage in whom added cortexin lowered serum IL-1beta 1.5-fold and TNF-alpha 1.4-fold in the severe subgroup, and 60 children aged 8–11 with dyslexia in whom cortexin improved reading, attention and working memory in 73.3% versus 60% on encephabol. None of these trials has been replicated outside Russia, and none used a placebo arm.
Randomized trials show no benefit
Cortexin has placebo-controlled trials in stroke, but independent review is negative. A 2023 Cochrane review of these cattle-brain drugs found no benefit on death rates (6 trials, 1,689 people), with moderate confidence. A rat study agreed.
▸Clinical wording
Cortexin has genuine randomised, placebo-controlled human data in ischaemic stroke, but the independent appraisal of it is unfavourable. A multicentre double-blind placebo-controlled Russian trial in 272 patients reported the best outcome with two 10-day courses of cortexin 10 mg three times daily, and an earlier double-blind placebo-controlled study in 62 patients with hemispheric ischaemic stroke reported benefit at 20 mg/day for 10 days. The 2023 Cochrane review of Cerebrolysin and Cerebrolysin-like agents incorporated that 272-patient Cortexin trial and concluded, with moderate-certainty evidence, that these cattle-brain peptide mixtures probably have no beneficial effect on all-cause death (RR 0.96, 95% CI 0.65 to 1.41; 6 trials, 1689 participants); Cochrane rated the Cortexin study at unclear risk of bias in all domains except incomplete outcome data, and none of the included trials reported death-or-dependence, quality of life or time to return to work. Independently, a blinded US laboratory comparison in a rat embolic stroke model found Cortexin 1.7 mg/kg produced functional outcomes and lesion volumes no different from saline, while only Cerebrolysin improved neurological outcome. A 2025 multicentre trial in 490 patients showed only that the intravenous form is non-inferior to the intramuscular form — both arms received cortexin, so it says nothing about efficacy against no treatment.
Large studies, but no control group
Evidence covers many patients but the design is weak: open-label, no comparison group. One Russian program gave cortexin to 500 people (average age 63.7) with low brain blood flow, reporting better memory-test scores but no control group.
▸Clinical wording
The cognitive-impairment evidence for cortexin is large in patient numbers but weak in design: the main studies are open-label observational programmes with no control group. An all-Russian screening programme applied cortexin 10 mg/day for 10 days to patients with chronic brain ischaemia across 70 cities in 2013 and analysed 500 of them (mean age 63.7 years), reporting regression of focal neurological symptoms and improvement on MMSE, the five-word test and the Schulte test; a separate multicentre observation of 309 patients aged 30–80 combined cortexin with citicoline, so the two drugs cannot be separated. In post-COVID cognitive complaints, the uncontrolled CORTEX programme treated 979 outpatients across four countries with 10 or 20 mg intramuscularly for 10 days, and a further study compared 52 treated patients against 57 untreated for concentration, executive function and auditory-verbal memory. The one setting with blinded, placebo-controlled MMSE data is acute stroke, where mean MMSE improved by about 4 points over 90 days in both cortexin arms of a non-inferiority trial that contained no placebo-only group.
Studied as add-on, not alone, in kids
Cortexin is studied as an add-on to seizure drugs, not alone; reports are open-label (unblinded). In 84 children with cerebral palsy and epilepsy, it more than halved seizures in many, though it worsened in one. Animal results are mixed.
▸Clinical wording
Cortexin is studied as an add-on to antiepileptic drugs rather than as an anticonvulsant in its own right, and every human report is open-label. In 84 children aged 1–11 with cerebral palsy combined with epilepsy, cortexin 5–10 mg intramuscularly added to antiepileptic drugs produced a more than twofold seizure reduction together with motor improvement in 36.9%, while 27.4% did not respond and seizure aggravation occurred in one girl with West syndrome (1.2%). A study of 86 children and adolescents aged 3–17 reported no aggravation of seizures in 95% and improved cognitive function in 65%, and a 12-month adult series of 64 patients given three 10-day courses reported reduced seizure frequency and improved EEG. Animal work is mixed rather than uniformly positive: in a rat pentylenetetrazole model, long-term pretreatment with cortexin had no effect on status epilepticus, while a dose-dependent antiepileptic effect appeared only in the chronic (kindling) convulsion model. Interpretation is limited by the absence of randomisation, blinding or any non-Russian replication.
Animal-only data, industry-linked
The strongest data come from rat studies co-authored by the maker's employees. In rats, it reduced dead brain tissue after stroke-like injury and improved test scores. An independent, blinded rat study found no better result than saline.
▸Clinical wording
The strongest mechanistic data for cortexin come from two rodent programmes co-authored with employees of the company that supplies the drug. In rat middle cerebral artery occlusion and chronic carotid stenosis models, cortexin at 1 or 3 mg/kg for 10 days reduced necrotic brain tissue volume, improved sensorimotor and cognitive test performance and preserved antioxidant enzyme activity; radiolabelled cortexin crossed the blood-brain barrier in mice reaching 6–8% of whole-blood concentrations, and in vitro it bound AMPA (80.1%), kainate (73.5%), mGluR1 (49.0%), GABA-A1 (44.0%) and mGluR5 (39.7%) receptors, pointing to glutamatergic and GABAergic actions. A 2025 study in rat offspring with developmental delay caused by late-pregnancy ethanol or neonatal ischemia-hypoxia found that intramuscular and rectal cortexin both reduced mNSS neurological deficit and cortical neuronal damage. These results conflict with the independent blinded rat embolic stroke comparison in which Cortexin performed no better than saline, so the preclinical picture is not consistent across laboratories.
Section 02
Mechanism of Action
A mixture, not a single molecule
- Cortexin is a cattle brain-cortex hydrolysate holding many small protein fragments, so it has no single mechanism.
- Labelled Cortexin crossed into mouse brain, reaching 6 to 8 percent of whole-blood levels.
- A later mouse study found similar brain levels after injection into muscle or delivery into the rectum.
▸Clinical wording
Composition and delivery to the brain
Cortexin is not a defined peptide but a hydrolysate of cattle cerebral cortex containing a mixture of low-molecular-weight polypeptides, so it has no single mechanism and its pleiotropy is attributed to that multi-component composition. Radiolabelled Cortexin crossed the blood-brain barrier in mice, reaching brain concentrations equal to 6-8 percent of whole-blood concentrations. A later study using Na-125I labelling in mice found similar brain distribution profiles after intramuscular and rectal administration, with brain levels tracking blood concentration rather than route.
Sticking to brain signal receivers
- Screened against a wide receptor panel, Cortexin bound strongly to two excitatory glutamate receptor types.
- It bound moderately to two other glutamate receptors and to a calming receptor (GABA-A1).
- This is displacement binding by an undefined mixture, not proof that it switches any receptor on or off.
- In an uncontrolled patient study after stroke, a blood marker of receptor breakdown fell during treatment.
▸Clinical wording
Binding to glutamatergic and GABAergic receptors in vitro
Screened against a wide receptor panel in vitro, Cortexin showed high or moderate binding to AMPA receptors (80.1 percent), kainate receptors (73.5 percent), mGluR1 (49.0 percent), GABA-A1 (44.0 percent) and mGluR5 (39.7 percent). The authors concluded that its in vivo effects could relate to glutamatergic and GABAergic actions. This is displacement binding by an undefined mixture, not a demonstration of functional agonism, antagonism or allosteric modulation at any of these receptors. A clinical correlate is that plasma NR2-peptide, a marker of NMDA receptor breakdown, fell over a treatment course in patients after ischaemic stroke in an uncontrolled observational study.
Blocking one cell-death trigger enzyme
- Cortexin blocked caspase-8, the enzyme that starts one cell-suicide pathway, in brain tissue.
- Its effect on several other protein-cutting enzymes was far weaker or absent.
- A much simpler fragment isolated from the drug retained the full blocking capacity.
- Both the whole drug and that fragment prevented nerve cell damage in a glutamate poisoning culture model.
▸Clinical wording
Caspase-8 inhibition and protection from glutamate toxicity
Cortexin effectively inhibited brain caspase-8, the initiator caspase of the extrinsic apoptotic pathway, while its effect on caspase-1, -3 and -9, cathepsin B and calpain was far weaker or absent — a protease-selective and tissue-specific profile. A peptide fraction of much simpler composition was isolated from the drug and retained the full inhibitory capacity of the original preparation. Both the whole drug and that fraction prevented neuronal damage in a culture model of glutamate-induced cell death, linking the biochemical finding to a cellular outcome.
Reducing oxidative damage in rat models
- In rats with sudden brain artery blockage, Cortexin reduced the amount of dead brain tissue.
- In chronic artery narrowing it improved antioxidant function and prevented severe nerve degeneration.
- After blood-flow restoration it lowered blood oxidant status and raised antioxidant status.
- In an accelerated-ageing rat model it restored oxidant balance and acted anti-inflammatorily.
▸Clinical wording
Oxidative stress and neuroinflammation in rodent models
In rat models of acute (middle cerebral artery occlusion) and chronic (carotid stenosis) brain ischaemia, Cortexin reduced the size of brain tissue necrosis in the acute model, improved antioxidant system function and prevented severe neurodegenerative change in the chronic model. In a rat cerebral ischaemia- reperfusion model it lowered serum total oxidant status and raised total antioxidant status, and reduced immunostaining for OPG, RANK, RANKL and the calcium channel TRPC1, all of which had been elevated by injury. In an accelerated-aging rat model it restored the pro-/antioxidant balance and acted anti-inflammatorily in brain and systemically.
Several unrelated proteins as suggested targets
- Three brain proteins have been identified as molecular partners of Cortexin peptides.
- They cover signal relay, energy metabolism and cell scaffolding rather than one shared pathway.
- Read with the enzyme-blocking result, the proposed targets are scattered across separate functions.
- Tissue specificity of these interactions is offered as the reason brain extracts act on brain.
▸Clinical wording
Proposed molecular partners in brain tissue
Neuron-specific proteins beta-5 tubulin, creatine kinase B and protein 14-3-3 alpha/beta have been identified as molecular partners of Cortexin peptides in the brain. Read together with the caspase-8 result, this places the proposed targets across signal transduction, energy metabolism, proteolytic protein modification and cytoskeletal structure rather than in one pathway, and the tissue specificity of these interactions is offered as the explanation for organ-specific effects of brain-derived hydrolysates.
Protecting nerve cells from high sugar
- Adult rat sensory nerve cells in dishes lost viability quickly under very high glucose.
- Adding Cortexin slowed that fall in proportion to concentration.
- Under normal sugar, Cortexin alone raised the same viability measure.
- This is an isolated sensory-neuron model and does not address brain neurons.
▸Clinical wording
Neuronal survival in culture
In primary cultures of adult rat dorsal root ganglion neurons, exposure to 50 mM glucose caused a rapid and sustained fall in a real-time impedance index of cell viability, attachment and neurite outgrowth. Co-treatment with Cortexin attenuated that fall in a concentration-dependent manner, and under normoglycaemic conditions Cortexin alone raised the index. This is an in vitro sensory-neuron model of hyperglycaemic injury and does not address central neurons.
Where the evidence contradicts itself
- Much of the clinical literature is Russian-language, observational or open-label rather than controlled.
- Several experimental papers were written or co-written by employees of the manufacturer.
- In one rat stroke study Cortexin lowered damage markers but left growth factor and dead tissue volume unchanged.
- A comparison of four brain-extract drugs found significant neurological benefit only for a different drug.
▸Clinical wording
Evidence base and conflicting findings
The evidence is uneven. Much of the clinical literature is Russian-language, observational or open-label, and several experimental studies are authored or co-authored by employees of the manufacturer. Findings conflict on key points: in a rat middle cerebral artery occlusion-reperfusion study Cortexin lowered TNF-alpha, Fas and Bax but did not change BDNF and did not significantly reduce necrosis volume, whereas Mexidol did both. A comparative analysis of four brain-hydrolysate drugs in a rat ischaemic stroke model reported significant neurological improvement over placebo only for cerebrolysin. Claims of neurotrophic-factor activation are not supported by the data located here.
Section 03
Biological Pathways
- Blood-brain barrier crossingRadiolabelled Cortexin crossed the blood-brain barrier in mice, reaching brain concentrations equal to 6 to 8 percent of whole-blood levels, with similar distribution found after intramuscular and rectal dosing.
- Glutamatergic and GABAergic bindingScreened in vitro, Cortexin showed high or moderate binding to AMPA, kainate, mGluR1, GABA-A1 and mGluR5 receptors, a displacement-binding profile rather than proven functional agonism or antagonism at any site.
- Caspase-8 inhibitionCortexin selectively inhibited brain caspase-8 with far weaker effect on caspase-1, -3, -9, cathepsin B and calpain; the whole drug and an isolated peptide fraction prevented damage in a glutamate-toxicity model.
- Oxidative stress in ischaemia modelsIn rat brain ischaemia models, Cortexin reduced tissue necrosis, raised antioxidant status, and lowered OPG, RANK, RANKL and TRPC1 staining elevated by injury, with anti-inflammatory effects in an aging model.
Section 04
Dosage Information
Complex mixture of polypeptides from porcine cerebral cortex| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Intramuscular — neurology indications | Russian registration label, adults | 10 mg once a day for 10 days — about 110–145 µg/kg at 70–90 kg; the vial is dissolved in 1–2 mL. Repeat course after 3–6 months. | Registered only in Russia and its neighbours; no FDA approval. The label covers brain disease, head injury and stroke under a doctor, not memory. |
| Intramuscular — after a stroke | Label regimen and a 272-patient placebo-controlled trial | 10 mg twice a day for 10 days, repeated after a 10-day gap — 20 mg a day, 400 mg per cycle, about 220–290 µg/kg at 70–90 kg | Cochrane pooled it with the Cerebrolysin trials: moderate-certainty evidence of little or no difference in deaths; no trial measured disability. |
| Intramuscular — children | Russian label, children's dose by body weight | 0.5 mg/kg a day for 10 days under 20 kg; the whole 10 mg vial above it. For delayed development and speech, cerebral palsy, epilepsy. | The adult 10 mg is that 0.5 mg/kg rule frozen at 20 kg. Carried up to adult weight it would be 35–45 mg — four times what the label gives an adult. |
| Intramuscular — self-administration | Use outside the registered indications | The label numbers repeated: 10 mg daily for 10 days, some reporting 10 mg twice daily, with a 3–4 week break before another course. | Practice copies the label dose, not its population. Cortexin was never tested in healthy adults — the schedule is borrowed from stroke patients. |
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
Lyophilised powder
Vials are kept in the original carton, protected from light, at no more than 25 °C; the manufacturer states a range of 2 to 25 °C. Shelf life is 3 years. Before injection the contents are dissolved in 1–2 ml of 0.5% procaine, water for injection or 0.9% sodium chloride, with the needle aimed at the vial wall so the solution does not foam.
After reconstitution
The prepared solution is not stored: the instruction forbids using a vial of dissolved product after storage. It is injected straight after preparation and the remainder is discarded.
Section 07
Side Effects & Precautions
Cortexin is a prescription-only medicine registered in Russia and other EAEU countries (Armenia, Belarus, Kazakhstan, Kyrgyzstan), not approved globally; ClinicalTrials.gov lists no trials for it. Its official leaflet lists adverse reactions with defined frequencies, from life-threatening to mild.
Two very rare, life-threatening reactions
The official leaflet lists anaphylactic shock and angioneurotic oedema of the larynx as very rare adverse reactions, affecting no more than 1 in 10,000 patients. Both require emergency medical care.
Sixteen further reactions, same rarity
The leaflet also lists sixteen further adverse reactions, all at the same very rare frequency of no more than 1 in 10,000.
- Allergic: drug allergy, skin redness, urticaria, rash, itching, allergic dermatitis.
- Injection site: redness and local warmth; pain and induration with intramuscular use.
- Cardiovascular: tachycardia, arrhythmia, raised blood pressure.
- Nervous system and mood: asthenia, chills, psychomotor agitation, impaired coordination, headache, dizziness, somnolence, hypoaesthesia, anxiety, insomnia.
Contraindications and other warnings
The 10 mg leaflet's only absolute contraindication is hypersensitivity to Cortexin or its excipients; procaine, used as the intramuscular diluent, carries its own contraindications and can itself cause reactions.
- Pregnancy: the 5 mg leaflet contraindicates it; the 10 mg leaflet only advises consulting a doctor - this reflects absent data, not demonstrated harm.
- Lidocaine must never be used as the diluent; it is linked to more frequent, more severe adverse reactions.
- The drug has a moderate effect on the ability to drive or operate machinery, due to possible psychomotor agitation and dizziness.
Approved for children, route restricted
In Russia and the EAEU countries above, Cortexin is approved from birth to 18 years for cognitive and developmental indications.
- In children and adolescents, the leaflet restricts the route to intramuscular only.
- Intravenous administration is permitted exclusively in adults with hemispheric ischaemic stroke.
- No dose adjustment is specified for hepatic or renal impairment: the adult dose and regimen apply unchanged in both groups.
Independent review found one small trial
The only independent systematic review located found just one eligible randomised trial, in 80 participants, judged at high risk of bias. That trial reported no adverse events or discontinuations, but its size and bias risk limit what it shows about safety.
Section 08
Regulatory Status
It has never been reviewed or approved by the FDA or the EMA, though, and its animal-derived formulation would face a different bar under those agencies' current standards.
Russia
Registered prescription nootropic since 2009
Cortexin holds Russian marketing authorisation Р N003862/02 (originally ЛСР-003190/09), issued to ООО «Герофарм» in 2009 and re-registered in 2018. It is dispensed by prescription for complex therapy of cerebrovascular disorders, effects of brain injury, encephalopathy, cognitive impairment, and developmental delay in children.
FDA / United States
Not approved; no application on record
Cortexin has never been submitted to the FDA and holds no US marketing approval. It is a polypeptide fraction extracted from bovine brain cortex, a formulation type that does not meet current FDA identity and quality-control standards for biologics.
EMA / European Union
Not approved; no EU authorisation
Cortexin has not gone through the EMA's centralised or any national EU assessment procedure and holds no marketing authorisation in the European Union.
Clinical evidence
Decades of use, but outside Western review
Clinical experience is concentrated in Russia over several decades, with an established pharmacovigilance record there. No independent toxicology and efficacy dossier meeting FDA or EMA standards has been published, and the animal-origin formulation raises batch-consistency questions those agencies would need addressed.
A marketing authorisation in one country does not extend to another, and a national approval is not the same as an FDA or EMA review. Regulatory status differs by jurisdiction and can change — check current official sources before relying on any of this.
Section 09
Research Studies
- [1]Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in ratsKurkin DV, Bakulin DA, Morkovin EI, Kalatanova AV, Makarenko IE, Dorotenko AR, Kovalev NS, Dubrovina MA, Verkholyak DV, Abrosimova EE, Smirnov AV, Shmidt MV, Tyurenkov IN. · PLoS ONE · 2021
- [2]Neurotropic Effects of Cortexin on Models of Mental and Physical Developmental DelayKurkin DV, Bakulin DA, Morkovin EI, Petrov VI, Strygin AV, Smirnov AV, et al. · Biomedicines · 2025
- [3]Peptide drug cortexin inhibits brain caspase-8 (in Russian)Yakovlev AA, Lyzhin AA, Khaspekov LG, Guekht AB, Gulyaeva NV. · Biomeditsinskaya Khimiya · 2017
- [4]Molecular mechanisms of brain peptide-containing drugs: cortexin (in Russian)Gulyaeva NV. · Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova · 2018
- [5]Cortexin modulates OPG/RANK/RANKL and TRPC1 expression in cerebral ischemia-reperfusion injuryGuven C, Turk A, Kocak S, Zencirci B, Yalcin A, Aydin H, Dogukan M. · Neurological Research · 2026
- [6]Cortexin Ameliorates High Glucose-Induced Neuropathy in Cultured Rat Sensory NeuronsYazar U, Ayar A. · Neuroendocrinology · 2023
- [7]The effect of neuroprotectors on the level of BDNF, tumor necrosis factor alpha and apoptosis markers in acute cerebrovascular accidents (in Russian)Shchulkin AV, Chernykh IV, Abalenikhina YV, Gatsanoga MV, Kochetkova DL, Kruzhalov NA, Krestinina EV, Yakusheva EN. · Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova · 2026
- [8]Comparative studies of neurotrophic drugs based on brain hydrolysates (in Russian)Gromova OA, Torshin IY, Stakhovskaia LV, Maiorova LA, Ostrenko KS. · Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova · 2019
- [9]The biomarkers of cerebral ischemia as a new method for the validation of the efficacy of cytoprotective therapy (in Russian)Dambinova SA, Aliev KT, Bondarenko EV, Ponomarev GV, Skoromets AA, Skoromets AP, Skoromets TA, Smolko DG, Shumilina MV. · Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova · 2017
Section 10
Frequently Asked Questions
The evidence splits by how rigorously it was tested. A 2023 Cochrane review pooling six trials (1,689 patients) of cortexin and similar cattle-brain peptide extracts found moderate-certainty evidence of no meaningful difference in death rates versus placebo, and rated the main cortexin stroke trial at unclear risk of bias. A separate blinded rat-stroke study found cortexin produced outcomes no different from saline. Most of the large, positive-looking cortexin studies from Russia are open-label with no placebo group, a weaker form of evidence.
In Russia it is registered for neurological conditions across paediatric and adult neurology — cerebral palsy, epilepsy as an add-on, delayed development, stroke recovery, traumatic brain injury and cognitive impairment. Most of the supporting studies are open-label observational programmes run within Russia rather than randomised, placebo-controlled trials, so its local registration reflects clinical practice more than a strong independent evidence base outside stroke.
The Russian label calls for 10 mg intramuscularly once a day for 10 days in adults, repeated after 3 to 6 months; the stroke regimen used in a 272-patient placebo-controlled trial was 10 mg twice a day for 10 days, repeated after a 10-day gap. Children under 20 kg are dosed at 0.5 mg/kg a day — a rule that, carried up to adult body weight, would give roughly 35-45 mg, about four times the flat adult dose actually used.
The material reviewed lists side effects as "minimal reported," a thin, largely uncontrolled evidence base rather than a confirmed clean safety record — most supporting studies were open-label without systematic adverse-event tracking. No specific adverse effect is documented in detail here.
No — cortexin is registered only in Russia and neighbouring countries and carries no FDA or equivalent Western regulatory approval. Its main placebo-controlled trial and other Russian data have been reviewed internationally, including by Cochrane, but that review did not change its regulatory status elsewhere.
Vials are kept in the original carton, protected from light, at 2 to 25°C, with a stated shelf life of 3 years — refrigeration is allowed but not strictly required within that range. Once dissolved in procaine, water or saline for injection, the solution is not stored at all: instructions call for using it immediately and discarding any leftover.
Both are hydrolysed animal-brain peptide mixtures reviewed together by Cochrane, which found neither had a clear mortality benefit across 1,689 pooled patients. In one independent blinded rat-stroke study, only Cerebrolysin improved neurological outcome and reduced lesion size — cortexin performed no better than saline in that same comparison.