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Cortexin

Tier 1 · Human trials
Also known as Cortexin peptide · Polypeptides of cerebral cortex

Human evidence includes randomized clinical trials in acute ischemic stroke (e.g., a 490-patient RCT comparing IV vs IM regimens; a Cochrane-reviewed RCT contributing 272 participants), so the strongest evidence present is Tier 1. However, this evidence is heavily caveated: nearly all clinical and mechanistic studies originate from Russian institutions, often with manufacturer (Geropharm) involvement, most literature is in Russian, and independent Cochrane/systematic reviews rate the evidence as low certainty and high risk of bias with no clear functional benefit demonstrated and a possible increase in non-fatal serious adverse events. Much supporting data is animal-based, in vitro, or from non-randomized observational human studies. There is no independent Western replication of proposed mechanisms.

Half-life
Not recorded
Routes
Intramuscular injection · Intravenous (studied in stroke RCT) · Rectal (animal studies)
Goals
Cognitive enhancement / nootropic · Neuroprotection · Recovery from stroke / brain injury · Pediatric neurodevelopment support
Cost / mg
Not recorded

How it works

Cortexin is not a single molecule but a mixture of small water-soluble polypeptides (roughly 1,000–10,000 Da) extracted from the cerebral cortex of young cattle and pigs, along with amino acids and trace elements. It is proposed to act as a broad, multi-target neuroprotectant. Laboratory studies suggest its peptides bind to receptors that handle the brain's main excitatory (glutamate) and inhibitory (GABA) signaling, which could dampen overexcitation (excitotoxicity). It is also reported to protect neurons from damaging factors like glutamate excess, calcium overload, and free radicals, to reduce a step in the cell-death (apoptosis) cascade, to support the brain's antioxidant and anti-inflammatory balance, and to encourage nerve-cell survival, growth, and connections in ways compared to natural growth factors. It is claimed to help balance neurotransmitters (including dopamine and serotonin). It is used clinically in Russia and CIS countries as an injectable for stroke, brain injury, cognitive problems, and pediatric developmental issues, though independent reviewers judge the human evidence weak.

Overview

Overview

Cortexin (also called Cortexin peptide or polypeptides of cerebral cortex) is a low-molecular-weight polypeptide fraction extracted from the cerebral cortex of cattle and pigs under 12 months of age. It is manufactured by the Russian company Geropharm and supplied as a lyophilizate for reconstitution and injection. Rather than a single defined molecule, Cortexin is a complex mixture of water-soluble polypeptides (roughly 1,000–10,000 Da), predominantly acidic and neutral (isoelectric points ~3.5–9.5), together with neuropeptides, amino acids and trace elements. Its exact composition is not standardized and varies by batch.

Proposed mechanism

Cortexin is described as a multi-target neuroprotectant. In vitro binding studies report interaction with glutamate receptors (AMPA, kainate, mGluR1, mGluR5) and the GABA-A receptor — at 10 μg/ml, reported binding was highest at AMPA (80.1%) and kainate (73.5%) receptors — which could modulate excitotoxicity and neuronal excitability. It is reported to inhibit brain caspase-8 (an apoptosis enzyme), interact with neuron-specific proteins (β5-tubulin, creatine kinase B, 14-3-3 α/β, actin), support antioxidant and anti-inflammatory balance, inhibit lipid peroxidation, modulate dopamine content, and provide BDNF-like/NGF-like neurotrophic support. The synthetic tetrapeptide Cortagen (Ala-Glu-Asp-Pro / AEDP) was developed as a key active analog of one Cortexin fraction.

Note: A separately named 82-amino-acid integral membrane protein 'cortexin' identified from rat cortex mRNA is a distinct molecule and should not be confused with the injectable drug.

Reported uses

Cortexin is marketed in Russia and CIS countries as an injectable neuroprotective, nootropic and cognitive-enhancing medicine and has been used clinically for decades across stroke, encephalopathy, traumatic brain injury, epilepsy, cognitive impairment, and pediatric developmental delay (including attention disorders and speech impairments).

Evidence

  • Animal models show fairly consistent neuroprotective and behavioral signals: reduced infarct volume in acute (MCAO) and chronic ischemia, reduced neuronal damage and neurological deficit in developmental-delay models, protection of sensory neurons against high-glucose damage in vitro, and reduced degeneration in traumatic facial nerve paralysis in rabbits.
  • Human studies include observational reports (post-Covid cognitive impairment, young post-stroke patients, a 635-child multicenter pediatric study) and randomized trials in acute ischemic stroke. A 490-patient RCT reported mRS 0–2 in 93.64% (IV regimen) vs 86.50% (all-IM) at day 90 and deemed IV and IM forms therapeutically equivalent.
  • Independent appraisal is far more cautious. A Cochrane assessment of the brain-peptide class urged caution without clear functional benefit in stroke, and systematic reviews rate Cortexin's cognitive evidence as low certainty / high risk of bias (essentially one eligible ~80-patient cognitive trial). Nearly all mechanistic and clinical data come from Russian institutions, often with manufacturer involvement; there is no independent Western replication of the proposed mechanisms.

Regulatory status

Cortexin is not approved by the FDA, EMA, or other Western regulators.

What the research shows

150 findings extracted from the 19 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 9 human trial findings, 14 human study findings, 30 animal findings, 1 in vitro finding and 1 expert opinion finding.

  • human trialNX210 may exert beneficial effects on the central nervous system, particularly in terms of cognitive processing4

  • human trialCortexin 10 mg IV administered twice daily for 10 days followed by Cortexin 10 mg IM twice daily for 10 days resulted in 93.64% of patients reaching 0-2 on the modified Rankin scale at day 90 in acute ischemic stroke5

  • human trialCortexin 10 mg IM administered twice daily for 10 days followed by Cortexin 10 mg IM twice daily for 10 days resulted in 86.50% of patients reaching 0-2 on the modified Rankin scale at day 90 in acute ischemic stroke5

  • human trialCortexin IV administration decreased NIHSS scores by 3.93 by end of follow-up period in acute ischemic stroke patients5

  • human trialCortexin IM administration decreased NIHSS scores by 3.72 by end of follow-up period in acute ischemic stroke patients5

  • human trialCortexin IV administration resulted in MMSE score improvement of 4.11 by study completion in acute ischemic stroke patients5

  • human trialCortexin IM administration resulted in MMSE score improvement of 3.88 by study completion in acute ischemic stroke patients5

  • human trialCortexin 10 mg IV and IM forms are therapeutically equivalent for treating functional, neurological and cognitive deficits in acute ischemic stroke5

Show 47 more findings

  • human trialCerebrolysin or Cortexin probably result in little to no difference in all-cause death7

  • human studyCortexin showed clinical effectiveness at a dose of 10 mg IM for 10 days1

  • human studyThe reliable effect of cortexin on cognitive impairment was shown in 635 patients aged 3-7 years across 4 clinical groups3

  • human studyThe best response to treatment was observed in patients with ADHD, aged 3-4 years, in particular on the tests measuring thinking3

  • human studyCortexin is effective for treatment of children with ADHD, speech delay and consequences of a perinatal lesion of the central nervous system3

  • human studyCortexin contributed to the restoration of psychomotor skills and correction of attention-deficit and hyperactivity signs in patients with ADHD3

  • human studyCortexin at 10 mg i.m. for 20 days improves concentration in post-Covid cognitive impairment patients6

  • human studyCortexin treatment increases control of exutative functions in post-Covid cognitive impairment6

  • human studyCortexin improves auditory-verbal memory in post-Covid cognitive impairment patients6

  • human studyCortexin is highly effective and safe for post-Covid cognitive impairment6

  • human studyCortexin treatment improves cognitive function in young patients (18-45 years) after ischemic stroke10

  • human studyCortexin improves attention, short-term memory, and executive functions10

  • human studyStatistical significance for cognitive improvement on MoCA was achieved by the end of the second course of Cortexin treatment10

  • human studyCortexin improves quality of life in post-stroke patients as measured by SF-36 questionnaire10

  • human studyChildren with autism, specific language impairment, attention deficit hyperactivity disorder and specific learning disorder show deficits in social competence18

  • animalCortexin administration reduced the severity of neurological deficits as measured by mNSS scores in models of developmental delay in rat offspring2

  • animalCortexin improved motor activity in the Open Field test in rat models of developmental delay2

  • animalCortexin enhanced performance in the Adhesive Removal and Rotarod tests in rat models of developmental delay2

  • animalCortexin decreased structural changes in brain tissues in rat models of developmental delay2

  • animalHistological examination revealed reduced neuronal damage in multiple cortical regions with cortexin treatment compared to placebo2

  • animalCortexin has neurotropic effects on models of mental and physical developmental delay2

  • animalCortexin (bovine brain cortex polypeptides) reduces severity of neurological deficits in rat models of developmental delay induced by ethanol toxicity, as measured by mNSS scores2

  • animalCortexin improves motor activity in Open Field test in rat models of developmental delay2

  • animalCortexin enhances performance in Adhesive Removal and Rotarod tests in rat models of developmental delay2

  • animalCortexin decreases structural changes in brain tissues of rats with developmental delay2

  • animalHistological examination revealed reduced neuronal damage in multiple cortical regions with increased normal, unchanged neurons in cortexin-treated rats compared to placebo2

  • animalCortexin exerts comparable neurotropic effects whether administered intramuscularly or rectally in rat models2

  • animalCortexin 0.25 mg/kg showed anxiolytic-like effects in the elevated plus maze (EPM) in acute testing8

  • animalCortagen 0.03 mg/kg enhanced locomotion both upon acute and after sub-chronic treatment8

  • animalCortagen 0.03 mg/kg had few effects on anxiety-related behavior8

  • animalAcute Cortexin treatment shows anxiolytic-like effects, while repeated treatment leads to anxiogenic-like arousal8

  • animalAcute and sub-chronic cortagen leads to motor stimulation with no side effects on emotional-affective profiles8

  • animalCortexin (1 or 3 mg/kg/day) improved recovery of neurological functions in rats with acute brain ischemia9

  • animalCortexin (1 or 3 mg/kg/day) reduced severity of sensorimotor and cognitive impairments in rats with acute brain ischemia9

  • animalCortexin reduced the size of necrosis of brain tissue in acute ischemia model in rats9

  • animalCortexin prevented the development of severe neurodegenerative changes in chronic ischemia model in rats9

  • animalCortexin at a dose of 1 and 3 mg/kg reduced the number of damaged neurons in the somatosensory region of the cerebral cortex9

  • animalCortexin® improved recovery of neurological functions in rodent models of acute and chronic brain ischemia12

  • animalCortexin® reduced the severity of sensorimotor and cognitive impairments in rats with brain ischemia12

  • animalCortexin® reduced the size of necrosis of brain tissue in acute ischemia models12

  • animalCortexin® prevented the development of severe neurodegenerative changes in chronic ischemia model12

  • animalCortexin at 3 mg/day intramuscularly for 10 days reduces neural fibrotic degeneration, myelin degeneration, and axonal degeneration in traumatic facial nerve paralysis in rabbits14

  • animalCortexin at 3 mg/day intramuscularly for 10 days reduces edema in traumatic facial nerve paralysis in rabbits14

  • animalCortexin significantly reduced collagen fiber increase to a greater extent than methylprednisolone in traumatic facial nerve paralysis in rabbits14

  • animalCortexin and methylprednisolone showed no significant difference in electromyography findings for traumatic facial nerve paralysis recovery in rabbits14

  • in vitroCortexin® has neuroprotective effects against high glucose-induced damage in primary cultured rat sensory neurons11

  • expert opinionCortexin (neuropeptides) has been used successfully in treating tics in paediatric patients based on local experience17

How it works

Based on 2 human trial findings, 1 human study finding, 15 animal findings, 18 in vitro findings, 5 expert opinion findings and 3 theoretical findings.

  • human trialNX210 is a linear peptide derived from subcommissural organ-spondin4

  • human trialNX210c may decrease the levels of homocysteine in plasma, a known independent risk factor for neurovascular diseases4

  • human studyCortexin has a neurocytoprotective effect6

  • animalCortexin is composed of bovine brain cortex polypeptides2

  • animalThe ability of the drug to modulate dopamine content in the brain was shown during experimental studies3

  • animalCortexin improved functioning of the antioxidant system in rat brain in acute ischemia9

  • animalCortexin® improved functioning of the antioxidant system in chronic ischemia model12

  • animalEffects of Cortexin® in vivo could be related to glutamatergic and GABAergic actions12

Show 36 more findings

  • animalCortexin restored the ratio of pro- and antioxidative systems in a model of accelerated aging in rats13

  • animalCortexin demonstrated a significant anti-inflammatory effect both in the brain and at the systemic level in accelerated aging rat model13

  • animalNeuron-specific proteins β5-tubulin, creatine kinase B and protein 14-3-3 α/β are molecular partners of cortexin peptides in the brain13

  • animalCortexin neuroprotective effects are associated with key processes underlying neuroplasticity including signal transduction, energy metabolism, proteolytic protein modification, cell structure, and neuroinflammation13

  • animalOn a model of accelerated aging in rats, cortexin restored the ratio of pro- and antioxidative systems13

  • animalCortexin demonstrated a significant anti-inflammatory effect both in the brain and at the systemic level in accelerated aging rat model13

  • animalNeuron-specific proteins β5-tubulin, creatine kinase B and protein 14-3-3 α/β were shown to be molecular partners of cortexin peptides in the brain13

  • animalCortexin at 3 mg/day intramuscularly for 10 days promotes normal myelin production in traumatic facial nerve paralysis in rabbits14

  • animalCortexin mRNA is present at significant levels in fetal brain with peak expression in postnatal rodent brain15

  • animalCortexin mRNA is detected primarily in neurons of rodent cerebral cortex but not in cells of the hindbrain or white matter regions15

  • in vitroCortexin comprises neuropeptides, amino acids and trace elements1

  • in vitroCortexin nucleoprotein complexes of the cerebral cortex can retain elements of chromatin with DNA fragments1

  • in vitroPeptide components of cortexin derived from animal brain interact with cellular and molecular targets to provide neuroprotection1

  • in vitroThree neuron-specific β5-tubulins (components of cytoskeleton microtubules) interact with cortexin in the brain3

  • in vitro14-3-3 α/β protein classified as an adapter protein influencing other peptides interacts with cortexin3

  • in vitroActin participating in neurons migration, reparation and differentiation (cytoskeleton protein) interacts with cortexin3

  • in vitroB-type creatine kinase is an enzyme of cell energy exchange that interacts with cortexin3

  • in vitroBoth Cortexin and Cortagen stimulate neural growth in vitro, presumably in association with neurotrophic factors8

  • in vitroCortexin (10 μg/ml) demonstrated high or moderate binding to AMPA receptors in vitro9

  • in vitroCo-treatment with Cortexin® attenuates high glucose-induced decrease in Cell Index in a concentration-dependent manner11

  • in vitroCortexin® treatment led to a concentration-dependent increase in Cell Index values under normoglycemic conditions11

  • in vitroCortexin® demonstrated high or moderate binding to AMPA-receptors, kainate receptors, mGluR1, GABAA1 and mGluR5 in vitro12

  • in vitroCortexin effectively and tissue-specifically inhibited brain caspase-8 in in vitro experiments13

  • in vitroIn in vitro experiments cortexin effectively and tissue-specifically inhibited brain caspase-813

  • in vitroCortexin is a novel integral membrane protein of 82 amino acids identified from rat cortex-enriched mRNA15

  • in vitroRat cortexin and mouse homologue show 98% similarity in amino acid sequence15

  • in vitroCortexin contains a conserved single membrane-spanning region in the middle of the sequence15

  • in vitroCortexin mRNA is brain-specific and cortex-enriched15

  • expert opinionCortexin is a complex of neuropeptids of animal origin with a mechanism of brain plasticity stimulation3

  • expert opinionPotential molecular mechanisms of cortexin neuroprotective effects are associated with key processes underlying neuroplasticity: signal transduction, energy metabolism, proteolytic protein modification, cell structure, and neuroinflammation13

  • expert opinionThe pleiotropicity of mechanisms of cortexin action is based on the composition of the drug containing a variety of neuropeptides13

  • expert opinionSocial cognition is a separate cognitive function with a role in the formation of normal mental development18

  • expert opinionTheory of mind has neurobiological foundations18

  • theoreticalCortexin components have a specific range of targets for correction of molecular and cellular processes at various stages of pathological process1

  • theoreticalCortagen (Ala-Glu-Asp-Pro peptide) is a synthetic analog of one Cortexin fraction8

  • theoreticalThe function of cortexin may be particularly important to neurons of both the developing and adult cerebral cortex15

Dosing

Based on 1 human trial finding, 1 human study finding and 4 animal findings.

  • human trialIn the subgroup with dosing schedule 30 mL for 10 days (cumulative dose 300 mL), the increase in non-fatal serious adverse events was more prominent7

  • human studyStandard treatment of cortexin includes 10 intramuscular injections3

  • animalCortexin was administered intramuscularly or rectally as suppositories for 20 days in the study2

  • animalCortexin can be administered intramuscularly or rectally as suppositories2

  • animalCortexin administered for 20 days showed efficacy in rat models2

  • animalPeptides are active in very low dosages with no side effects8

How the body handles it

Based on 9 human trial findings, 7 animal findings and 1 expert opinion finding.

  • human trialNX210 has a short half-life in plasma of 6–20 min4

  • human trialNX210 has high apparent volume of distribution of 1870–4120 L4

  • human trialNX210 has rapid clearance of 7440–16,400 L/h4

  • human trialIn plasma, tryptophan showed dose-related increase with NX2104

  • human trialIn plasma, homocysteine showed dose-related decrease with NX2104

  • human trialDecreased blood glutamate and increased glutamine were observed in NX210 treated participants versus placebo4

  • human trialEEG showed statistically significant decrease in beta and gamma bands with NX2104

  • human trialEEG showed dose-dependent increasing trend in alpha bands with NX2104

Show 9 more findings

  • human trialPharmacodynamic effects were sustained for several hours in plasma or 48 h in urine and EEG4

  • animalCortexin administered intramuscularly or rectally can reach the systemic circulation and cross the blood-brain barrier2

  • animalBrain tissue distribution of radiolabeled cortexin is primarily dependent on its blood concentration and influenced by route of administration2

  • animalBrain polypeptides (cortexin) can reach systemic circulation and cross the blood-brain barrier2

  • animalDistribution of cortexin in brain tissues is primarily dependent on its blood concentration, which is influenced by route of administration2

  • animalRadioactively labeled Cortexin crossed the blood-brain barrier in mice in vivo with concentrations equal to 6–8% of concentrations found in whole blood9

  • animalRadioactively labeled Cortexin® crossed the blood-brain barrier in mice in vivo with concentrations equal to 6-8% of concentrations found in whole blood12

  • animalCortexin® readily crosses the blood-brain barrier in mice12

  • expert opinionSince the drug has polypeptide nature, it is impossible to conduct properly pharmacokinetics studies3

Safety and side effects

Based on 9 human trial findings, 4 human study findings and 3 animal findings.

  • human trialAll dosages of NX210 (0.4, 1.25, 2.5, 5, and 10 mg/kg intravenously) were safe and well tolerated4

  • human trialAll treatment-emergent adverse events (n = 17) were of mild severity and resolved spontaneously4

  • human trialTwelve treatment-emergent adverse events (70.6%) were deemed drug related4

  • human trialSeven drug-related adverse events (58.3%) concerned nervous system disorders including dizziness, headache, and somnolence4

  • human trialIntravenous and intramuscular forms of Cortexin show comparable safety profiles in acute ischemic stroke patients5

  • human trialCerebrolysin or similar peptide mixtures may result in little to no difference in non-death attrition7

  • human trialCerebrolysin probably results in little to no difference in the total number of people with serious adverse events7

  • human trialThere is an increase in the total number of people with non-fatal serious adverse events with Cerebrolysin7

Show 8 more findings

  • human trialCerebrolysin or similar peptide mixtures may result in little to no difference in the total number of people with adverse events7

  • human studyCortexin demonstrated comparable safety between two dosage forms1

  • human studyThe tolerability of cortexin was good3

  • human studyNo adverse events were observed in Cortexin treatment group6

  • human studyCortexin is safe and well tolerated in young people with cognitive deficits in the poststroke period10

  • animalCortexin 0.25 mg/kg had no locomotor effects over 4 days8

  • animalCortexin 1.00 mg/kg led to development of hyperactivity8

  • animalFollowing a sub-chronic regimen (5 days), Cortexin reference dose and other doses of cortagen produced anxiogenic effects8

What people use it for

Based on 1 human trial finding, 1 animal finding, 4 expert opinion findings and 2 theoretical findings.

  • human trialCortexin contributed 272 participants in an RCT for acute ischaemic stroke treatment7

  • animalCortexin is effective for healing traumatic facial nerve paralysis with intact nerve integrity14

  • expert opinionCortexin is a polypeptide extract, used in clinics for its effects on memory, attention, and brain cortical processes8

  • expert opinionCortexin is a peptide hydrolysate derived from animal brain used for treatment of cerebral pathologies13

  • expert opinionCortexin is used for correcting cognitive and emotional disorders16

  • expert opinionNeurocognitive deficits in violation of social cognition in children may be subject to pharmacological correction18

  • theoreticalBehavioral stimulation from cortagen may find beneficial employment in the treatment of affective/depressive symptoms in humans8

  • theoreticalCortexin® may have clinical implications for diabetes-associated peripheral neuropathy11

Other findings

Based on 1 human trial finding, 1 in vitro finding and 2 expert opinion findings.

  • human trialCortexin is a Cerebrolysin-like agent7

  • in vitroCortexin is a lyophilized extraction of animal cortex1

  • expert opinionCortexin comes from the brain tissues of beeves3

  • expert opinionCortexin is sold in a form of lyophilizate3

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Limited evidence

Most evidence is Russian, animal-based, or manufacturer-linked with little Western replication

Nearly all mechanistic and clinical studies originate from Russian institutions, often with manufacturer involvement, and most literature is in Russian. There is no independent Western replication of proposed mechanisms, human physiology translation is largely unconfirmed outside Russian trials, and much positive data comes from animal models or observational (non-randomized) human studies (Cortexin Peptide: Evidence, Mechanism, Safety | PeptideStat, Cortexin: 28 Studies Reviewed (2026) | PepCodex).

Limited evidence

Pharmacokinetics are essentially uncharacterized

Because Cortexin is an undefined multi-component polypeptide mixture, sources state its human elimination half-life is not established and that proper pharmacokinetic studies cannot be conducted; BBB penetration is claimed from animal tracer studies (6–8% of blood levels) but is described as not rigorously characterized by Western standards (Cortexin: Mechanism, Status, Dose Reference & Half-Life | PeptideStat, Cortexin: 28 Studies Reviewed (2026) | PepCodex, Results of a multicenter study on the efficacy of cortexin in treatment of cognitive dysfunction in children - MedCrave online).

Other

Product identity is inconsistent: 'Cortexin' peptide drug vs a distinct 82-amino-acid membrane protein

Most sources describe Cortexin as an undefined mixture of low-molecular-weight polypeptides (1,000–10,000 Da) from animal cortex. However, Identification of cortexin: a novel, neuron-specific, 82-residue membrane protein enriched in rodent cerebral cortex. uses 'cortexin' to describe a specific, distinct entity — a novel 82-amino-acid integral membrane protein identified from rat cortex mRNA — which is a different molecule from the injectable drug and should not be conflated with it.

Other

One source (Safety, Tolerability, Pharmacokinetics and Initial Pharmacodynamics of a Subcommissural Organ-Spondin-Derived Peptide: A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose First-in-Human Study | Neurology and Therapy | Springer Nature Link) concerns NX210, a different peptide, not Cortexin

Safety, Tolerability, Pharmacokinetics and Initial Pharmacodynamics of a Subcommissural Organ-Spondin-Derived Peptide: A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose First-in-Human Study | Neurology and Therapy | Springer Nature Link reports safety and pharmacokinetic data (half-life 6–20 min, adverse events, EEG effects) for NX210, a linear peptide derived from subcommissural organ-spondin. These findings pertain to NX210, not Cortexin, and no Cortexin claims were drawn from it.

Contested

Behavioral safety signal: Cortexin causes hyperactivity/anxiogenic effects at higher or repeated doses in animals

While acute low-dose Cortexin showed anxiolytic-like effects, higher doses (1.00 mg/kg) produced hyperactivity and sub-chronic dosing produced anxiogenic arousal in rats (Modulatory Effects of Cortexin and Cortagen on Locomotor Activity and Anxiety-Related Behavior in Mice, Cortexin: Mechanism, Status, Dose Reference & Half-Life | PeptideStat). This contrasts with human tolerability reports of no or very rare adverse events (Cortexin®, Results of a multicenter study on the efficacy of cortexin in treatment of cognitive dysfunction in children - MedCrave online, [Neuprotection of post-acute COVID-19 cognitive impairment].).

Using it with other compounds

Check a stack
  • SemaxComplementary

    May be complementary

    Cortexin supports neuronal survival through anti-excitotoxic, anti-apoptotic and neurotrophic actions, while Semax (an ACTH fragment) drives BDNF/NGF-TrkB signaling and cognitive enhancement by a distinct mechanism. Both converge on neuroprotection, neurogenesis and improved memory/attention, so they can complement each other rather than overlap.

    Tier 4Theoretical — not established

    Shares dopaminergic system · anti inflammatory · neurogenesis · BDNF signaling

  • SelankComplementary

    May be complementary

    Both influence GABAergic tone and neurotransmitter balance and support BDNF signaling, but by different routes — Cortexin protects against glutamate excitotoxicity and Selank adds anxiolytic GABA-A/serotonergic modulation plus enkephalinase inhibition. Together they cover both the neuroprotective and the calm/anxiolytic side of brain function.

    Tier 4Theoretical — not established

    Shares dopaminergic system · anti inflammatory · GABA signaling · BDNF signaling

  • P21Complementary

    May be complementary

    P21 is a CNTF fragment that strongly upregulates BDNF and hippocampal neurogenesis while reducing tau phosphorylation, whereas Cortexin provides broad neurotrophic and anti-excitotoxic protection. Different upstream mechanisms both feeding neuroplasticity and neuronal survival, so the two are complementary.

    Tier 4Theoretical — not established

    Shares neurogenesis · BDNF signaling

  • NoopeptComplementary

    May be complementary

    Cortexin modulates AMPA/glutamate signaling and protects neurons from excitotoxicity, while Noopept positively modulates AMPA receptors and raises BDNF/NGF via its cycloprolylglycine metabolite. They act on overlapping glutamatergic/neurotrophic machinery through distinct entry points, making them a plausible complementary nootropic pairing.

    Tier 4Theoretical — not established

    Shares anti inflammatory · BDNF signaling

  • DavunetideComplementary

    No documented conflict

    Davunetide stabilizes microtubules and reduces tau pathology while adding anti-apoptotic, anti-inflammatory and neurotrophic protection; Cortexin brings anti-excitotoxic, antioxidant and caspase-8 anti-apoptotic support. Different molecular targets converging on neuronal survival, so they complement rather than duplicate each other.

    Tier 4Theoretical — not established

    Shares anti inflammatory

  • DSIPComplementary

    Worth caution

    Both enhance GABAergic tone and dampen glutamate/NMDA excitatory signaling, giving overlapping anti-excitotoxic and calming effects — DSIP primarily to deepen slow-wave sleep, Cortexin to protect neurons. Their converging effects on the excitation/inhibition balance make them a reasonable complementary pairing, though additive sedation should be monitored.

    Tier 4Theoretical — not established

    Timing DSIP is best dosed in the evening for sleep; watch for additive calming/sedative effects.

    Shares GABA signaling

  • SS-31Complementary

    May be complementary

    SS-31 protects neurons at the mitochondrial level (cardiolipin/ETC stabilization, reduced mitochondrial ROS), while Cortexin provides receptor-level anti-excitotoxic, antioxidant and anti-apoptotic protection. Two different arms of neuroprotection (energy metabolism vs. glutamate/apoptosis) that plausibly complement one another.

    Tier 4Theoretical — not established

    Shares anti inflammatory · BDNF signaling

  • DihexaComplementary

    May be complementary

    Cortexin provides BDNF/NGF-like neurotrophic support and synaptic plasticity through a polypeptide mixture, complementing Dihexa's targeted HGF/c-Met synaptogenesis. Distinct mechanisms converging on neuronal survival and cognition.

    Tier 4Theoretical — not established

    Shares BDNF signaling · neurogenesis · anti inflammatory

  • CerebrolysinSame mechanism

    Worth caution

    Both are enzymatically-digested animal-brain peptide mixtures (bovine/porcine cortex) working as broad neurotrophic-factor mimics — anti-apoptotic, anti-excitotoxic, anti-inflammatory, and pro-neuroplasticity. Because they occupy almost the same conceptual niche, running both together is largely redundant rather than additive, and it becomes impossible to tell which product is responsible for any benefit or side effect. Most users should pick one crude neurotrophic mixture rather than stack the two.

    Tier 4Theoretical — not established

    Shares anti inflammatory · neurogenesis · dopaminergic system · BDNF signaling

Safety and side effects

Safety and tolerability

Per the product labeling, undesirable reactions in clinical use are described as occurring very rarely (less than 1 in 10,000) and include:

  • Allergic/hypersensitivity reactions: anaphylactic shock, angioedema, erythema, urticaria, rash, pruritus, allergic dermatitis
  • Neurological/CNS: psychomotor agitation, incoordination, headache, dizziness, drowsiness

Pregnancy: Contraindicated due to lack of clinical study data.

Reported tolerability

Observational studies reported good tolerability in children, no adverse events in post-Covid cognitive impairment patients, and good safety/tolerability in young post-stroke patients. An RCT reported comparable safety between the IV and IM dosage forms in acute ischemic stroke. The manufacturer states safety is confirmed through practical use by millions of patients in Russia and abroad.

Independent safety signals and caveats

  • A Cochrane review of the peptide-mixture class (Cerebrolysin/Cortexin) found probably little to no difference in total serious adverse events (RR 1.16, 95% CI 0.81–1.66) or total adverse events (RR 1.03, 95% CI 0.92–1.14), but an increase in non-fatal serious adverse events (RR 2.39, 95% CI 1.10–5.23), which was more prominent in a higher cumulative-dose subgroup (RR 2.87, 95% CI 1.24–6.69). This serious-adverse-event signal, however, comes almost entirely from Cerebrolysin trials — the higher-dose subgroup used a 30 mL/day for 10 days (300 mL cumulative) Cerebrolysin regimen, dosed by volume rather than in milligrams as Cortexin is — so it cannot be attributed specifically to Cortexin, which contributed only 272 participants and mostly to the all-cause death comparison. It also found probably little to no difference in all-cause death (RR 0.96, 95% CI 0.65–1.41).
  • Animal behavioral signal: acute low-dose Cortexin (0.25 mg/kg) showed anxiolytic-like effects, but higher dose (1.00 mg/kg) produced hyperactivity and sub-chronic (5-day) dosing produced anxiogenic-like arousal — contrasting with the very-rare-adverse-event profile reported in humans.
  • Composition variability: the exact peptide composition is not standardized and varies by batch.
  • Overarching caveat: manufacturer/observational efficacy claims conflict with independent reviews finding no clear functional benefit and possible harm; the evidence base is largely Russian, animal-based, or manufacturer-linked, with limited Western replication.

Animal-source (prion/TSE) consideration

Because Cortexin is extracted from the cerebral cortex of cattle and pigs, it carries the theoretical concern common to all injectables made from animal central-nervous-system tissue: the possibility of transmitting a prion-related disease such as transmissible spongiform encephalopathy (the class that includes bovine spongiform encephalopathy, or "mad cow disease"). The manufacturer states that the source material is sourced from young animals and that the production process is controlled to exclude prion contamination, and no such transmission has been reported. This risk is therefore regarded as theoretical rather than demonstrated, but it is an inherent consideration for any brain-derived biological product and is one reason such preparations face regulatory scrutiny in Western markets.

Reconstitution and handling

Preparation

No dose has been established for this compound. No regulatory label exists for it, so the figures below are what sources report — not guidance.

Cortexin is supplied as a lyophilizate (freeze-dried powder) for reconstitution before injection. Each vial also contains 12 mg of glycine as a stabilizer. It is available in separate strengths: an adult 10 mg vial and a pediatric 5 mg vial. The reconstituted solution is administered by intramuscular injection in standard clinical use (intravenous administration has also been studied in stroke).

Reported dosing (from Russian clinical use / expert sources — not Western-approved regimens)

  • Standard adult: 10 mg once daily intramuscularly for 10 days.
  • Pediatric: children under 20 kg receive 0.5 mg/kg; children over 20 kg receive 10 mg, once daily for 10 days.
  • Hemispheric ischemic stroke (acute/early recovery): 10 mg twice daily (morning and afternoon) intramuscularly for 10 days, with a second course after 10 days and a repeat course after 3–6 months.
  • Stroke RCT regimen: 10 mg IV twice daily for 10 days, then 10 mg IM twice daily for 10 days.
  • Clinical effectiveness has also been reported at 10 mg IM for 10 days, and at 10 mg IM for 20 days in observational cognitive studies.

Treatment is typically given as a short daily course (commonly ~10 days or 10 injections). Because Cortexin is a multi-component polypeptide mixture with no well-characterized elimination half-life, daily dosing is used.

Preclinical dosing

Animal studies used approximately 0.5 mg/kg to 1–3 mg/kg IM, administered intramuscularly or rectally over 10–20 days; intramuscular and rectal routes produced comparable neurotropic effects in rat developmental-delay models.

These figures are reported from the manufacturer and Russian clinical/preclinical literature. Cortexin is not an FDA/EMA-approved drug, and this information is for research context only, not dosing guidance.

Sources

Ordered by evidence quality — the strongest first.

  1. [Cortexin. Molecular mechanisms and targets of neuroprotective activity](opens in a new tab)
    Tier 1Web · researchgate.net
  2. Neurotropic Effects of Cortexin on Models of Mental and ...(opens in a new tab)
    Tier 1Web · pmc.ncbi.nlm.nih.gov
  3. Results of a multicenter study on the efficacy of cortexin in treatment of cognitive dysfunction in children - MedCrave online(opens in a new tab)
    Tier 1Web · medcraveonline.com
  4. Safety, Tolerability, Pharmacokinetics and Initial Pharmacodynamics of a Subcommissural Organ-Spondin-Derived Peptide: A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose First-in-Human Study | Neurology and Therapy | Springer Nature Link(opens in a new tab)
    Tier 1Web · link.springer.com
  5. [Therapeutic equivalence of intravenous and intramuscular dosage forms of Cortexin in ischemic strokes].(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2025
  6. [Neuprotection of post-acute COVID-19 cognitive impairment].(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2024
  7. Cerebrolysin for acute ischaemic stroke.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  8. Modulatory Effects of Cortexin and Cortagen on Locomotor Activity and Anxiety-Related Behavior in Mice(opens in a new tab)
    Tier 2Web · benthamopenarchives.com
  9. Neuroprotective action of Cortexin, Cerebrolysin and ... - PMC(opens in a new tab)
    Tier 2Web · pmc.ncbi.nlm.nih.gov
  10. [Post-stroke cognitive impairment in young patients].(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2024
  11. Cortexin® Ameliorates High Glucose-Induced Neuropathy in Cultured Rat Sensory Neurons.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  12. Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in rats.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2021
  13. [Molecular mechanisms of brain peptide-containing drugs: cortexin].(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2018
  14. Efficacy of Cortexin and Methylprednisolone on Traumatic Facial Nerve Paralysis.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2016
  15. Identification of cortexin: a novel, neuron-specific, 82-residue membrane protein enriched in rodent cerebral cortex.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1993
  16. Neurological Aspects of the Sequelae of COVID-19 in Children.(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  17. [Tics and Tourette's syndrome in children].(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 2020
  18. [Disorders of social cognition in children].(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  19. [Dyslexia as a multideficit disorder].(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 2020

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