Pinealon

Also known as: EDR peptide, Glu-Asp-Arg, T-33, EDR tripeptide

Short synthetic regulatory tripeptide / neuropeptide bioregulator

What it is

Pinealon (Glu-Asp-Arg) is a short synthetic tripeptide that penetrates the cell and its nucleus, where it interacts with histone proteins and/or RNA and binds DNA — preferentially at CNG and CAG nucleotide sequences — potentially exerting epigenetic regulation of gene activity (PMID 22117547, PMID 10). Molecular docking studies indicate it binds the CCTGCC nucleotide sequence in the 5-tryptophan hydroxylase gene, epigenetically stimulating serotonin synthesis in brain cortex cells. In vitro, pinealon demonstrates dose-dependent restriction of reactive oxygen species (ROS) accumulation in cerebellar granule cells, neutrophils, and PC12 cells, decreases necrotic cell death, and modulates the ERK 1/2 pathway and cell cycle. It is proposed to stimulate antioxidant enzyme synthesis (SOD2, GPX1), modulate MAPK/ERK signaling, and reduce proapoptotic proteins (caspase-3, p53). In animal hypoxia models, its neuroprotective effect is attributed not primarily to direct ROS inhibition but to stimulation of internal antioxidant enzyme systems and possible limitation of NMDA excitotoxicity. In brain hypoxia models, pinealon promotes neurogenesis and decreases neuroinflammatory reactions. It also promotes accumulation of adrenergic mediators and serotonin in rat brain cortex under stress conditions. In pineal gland organotypic cultures, Glu-Asp-Arg (pinealon) does not affect expression of apoptosis marker AIF. The peptide can partly penetrate into the major groove of DNA, affecting guanine N7 and O6 atoms; Mg²⁺ ions promote this interaction.

Class: Short synthetic regulatory tripeptide / neuropeptide bioregulator

What it's studied for

Neuroprotection and anti-aging (geroprotection) Mixed
- Review comparing polypeptide complexes and short peptides (including pinealon) as neuroprotectors in elderly and aged populations, describing clinical application and molecular mechanisms of neuroprotective activity. PMID 24738258 Umnov et al., Advances in gerontology, 2013
- In 32 patients aged 41–83 with polymorbidity and organic brain syndrome, pinealon and vesugen showed significant anabolic effect, improved CNS activity, and slowed biological aging markers. Prooxidant activity detected by chemiluminescence. Did not affect chromatin condensation. Vesugen showed more visible geroprotecti PMID 26390612 Meshchaninov et al., Advances in gerontology, 2015
- In 110 subjects across age groups, combined use of oligopeptides containing glutamyl-asparagin-arginine (pinealon) and lysyl-glutamyl-asparagin (vezugen) showed most pronounced positive impact on biological age indicators. Oligopeptide drugs were among the safest interventions assessed. PMID 28539017 Myakotnykh et al., Advances in gerontology, 2016
- Pinealon (100 mcg capsule, 2 times daily for two weeks) improved parameters of biological age and indicators of adaptive reactions in workers of locomotive brigades. PMID 22708445 Nazimko et al., Advances in gerontology, 2012
Cognitive function improvement and learning Animal studies only
- Pinealon had prevalent positive effect on learning in both young and old rats in the Morris labyrinth compared to cortexin; linked to modulation of caspase-3 activity in brain structures. PMID 28976148 Mendzheritski et al., Advances in gerontology, 2013
- Administration of pinealon to pregnant rats with hyperhomocysteinemia significantly improved offspring cognitive function (spatial orientation and learning ability) and increased cerebellar neuron resistance to oxidative stress. PMID 22567179 Arutjunyan et al., International journal of clinical and experimental medicine, 2012
- Review: EDR peptide (Glu-Asp-Arg) interferes with elimination of dendritic spines in neuronal cultures from mice with Alzheimer's and Huntington's diseases; normalizes behavioral responses in animal studies; improves memory issues in elderly patients. PMID 33396470 Khavinson et al., Molecules, 2020
Antihypoxic / neuroprotection under hypoxia Animal studies only
- Among short regulatory peptides (vilon, epitalon, vesugen, pinealon), pinealon showed the most pronounced antihypoxic effect in a model of hypobaric hypoxia. Effect attributed to stimulation of antioxidant enzyme systems and possible limitation of NMDA excitotoxicity rather than direct ROS inhibition. PMID 18546825 Kozina, Advances in gerontology, 2008
- Pinealon and cortexin both promoted accumulation of adrenergic mediators in rat brain under acute hypobaric hypoxia and serotonin in cerebral cortex under mild hypothermia, potentially underlying geroprotective effects. PMID 28509493 Mendzheritsky et al., Advances in gerontology, 2015
- In old rats under sharp hypoxic hypoxia, pinealon promoted neurogenesis increase and decreased neuroinflammatory reactions (IL-6, TNF-α) toward reference levels. PMID 25051764 Mendzheritsky et al., Advances in gerontology, 2014
- Short peptides including pinealon promoted survival in old rats with modeled carotid artery occlusion. Pinealon moderately raised caspase-3 activity in false-operated animals and in occlusion model. PMID 21809624 Mendzheritsky et al., Advances in gerontology, 2011
Antioxidant / cytoprotective activity Mixed
- Pinealon (Glu-Asp-Arg) dose-dependently restricted ROS accumulation in cerebellar granule cells, neutrophils, and PC12 cells and decreased necrotic cell death. ERK1/2 activation delayed; cell cycle modified. PMID 21978084 Khavinson et al., Rejuvenation research, 2011
- Pinealon stimulated internal antioxidative enzyme systems in hypoxia models in rats. PMID 18546825 Kozina et al., Advances in gerontology, 2008
- In vitro: pinealon and other short peptides did not demonstrate direct antioxidant activity but restricted lipid peroxidation in human lipoproteins by modifying their structure. Increased stability of red blood cell membranes to osmotic hemolysis. Elevated stationary intracellular ROS levels while decreasing percentage PMID 18546826 Kozina et al., Advances in gerontology, 2008
- Pinealon decreased ROS accumulation and number of necrotic cells in cerebellar neurons from offspring of hyperhomocysteinemic rats. PMID 22567179 Arutjunyan et al., International journal of clinical and experimental medicine, 2012
Psychoadaptive and neurobehavioral correction in occupational settings Human observational
- Combined application of cytogens (pinealon and vezugen) restored adaptive potential, improved psychoemotional indices, intensified resistance to work stress, and reduced occupational risk of borderline mental disorders in lorry-drivers (p < 0.001–0.05). PMID 23734521 Bashkireva & Artamonova, Advances in gerontology, 2012
- Small peptides (cytogens) including pinealon, as part of preventive medical nutrition, improved work ability index (WAI) and adaptive resources in workers exposed to occupational hazards. PMID 28509489 Bashkireva & Kachan, Advances in gerontology, 2015
- Pinealon use (100 mcg capsule, 2 times daily for two weeks) confirmed positive effect on biological age parameters and adaptive reactions in locomotive brigade workers. PMID 22708445 Nazimko et al., Advances in gerontology, 2012
Epigenetic/DNA interaction and gene expression regulation In vitro only
- FITC-labeled pinealon (Glu-Asp-Arg) penetrated into cytoplasm, nucleus, and nucleolus of HeLa cells. Pinealon preferentially binds CAG- and CNG-containing deoxyribooligonucleotide sequences, recognizing cytosine methylation status. Site-specific DNA interaction may epigenetically control cell genetic functions. PMID 22117547 Fedoreyeva et al., Biochemistry (Biokhimiia), 2011
- EDR (Glu-Asp-Arg) can partly penetrate into the major groove of DNA, affecting N7 and O6 of guanine. Mg²⁺ ions promote DNA-EDR interaction by screening phosphate group charges. PMID 30762356 Silanteva et al., Journal of Physical Chemistry B, 2019
- Glu-Asp-Arg stimulated serotonin expression in aging cultures of brain cortex cells via epigenetic regulation of 5-tryptophan hydroxylase gene (CCTGCC complementary sequence identified by molecular docking). PMID 24909721 Khavinson et al., Bulletin of experimental biology and medicine, 2014
Cell proliferation stimulation in skin tissue Animal studies only
- Tripeptide T-33 (Glu-Asp-Arg, pinealon) produced a stimulating effect on cell proliferation in skin explants from young rats, associated with less pronounced apoptosis (p53 expression). Less clear effect in old rat explants. PMID 22803085 Voicekhovskaya et al., Bulletin of experimental biology and medicine, 2012
Possible role in Alzheimer's disease pathogenesis modulation Mixed
- Review: EDR peptide (Glu-Asp-Arg) activates gene expression and protein synthesis involved in neuronal functional activity, reduces apoptosis, interferes with dendritic spine elimination in Alzheimer's and Huntington's disease neuronal cultures, and promotes antioxidant enzyme synthesis in rat cerebellum neuron culture PMID 33396470 Khavinson et al., Molecules, 2020
Serotonin expression stimulation in pineal gland In vitro only
- In organotypic pineal gland culture from 3-month-old rats, Glu-Asp-Arg (pinealon) did not affect expression of apoptosis marker AIF or proliferative protein Ki-67. It did not stimulate CGRP synthesis. (Tissue-specific effects varied among peptides tested.) PMID 22803060 Khavinson et al., Bulletin of experimental biology and medicine, 2011
Circadian and mitochondrial regulation (orthopaedic recovery context) Animal studies only
- Narrative review notes pinealon as a recovery-enhancing agent targeting circadian and mitochondrial regulators, with preclinical promise but no current clinical trials in orthopaedic context. PMID 41490200 Rahman et al., Journal of the American Academy of Orthopaedic Surgeons, 2026

Community-reported dosing

Route	Dose	Frequency / Duration	Population / context	Source tier
Oral (capsule)	1 capsule containing 100 mcg of Pinealon, 2 times a day	Two weeks	human	Research PMID 22708445
Intraperitoneal (inferred from MeSH: Injections, Intraperitoneal)	Not explicitly stated (short peptide administered before carotid artery occlusion)	Not stated	animal	Research PMID 21809624
In vitro (cell culture)	Dose-dependent concentrations tested (specific concentrations not numerically stated in abstract)	Not stated	in_vitro	Research PMID 21978084
Not explicitly stated	Not explicitly stated (pinealon administered to pregnant rats)	During pregnancy (methionine loading period)	animal	Research PMID 22567179
Not stated	Not explicitly stated	Not stated	human	Research PMID 26390612
Not stated	Not explicitly stated	Not stated	human	Research PMID 28539017
Not stated	Not explicitly stated	Not stated	human	Research PMID 23734521
subcutaneous injection	100 mcg	once daily	biohackers and longevity-focused users following Khavinson-derived peptide protocols	[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection	100 mcg	once daily	biohackers and longevity-focused users seeking extended course for deeper neuroprotective effect	[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection	200 mcg	once daily	experienced biohackers self-experimenting with higher-end dosing	[S] Claude Sonnet 4.6 — synthesized from aggregate training data
oral (sublingual capsule / tablet)	10 mg	once daily	longevity-focused biohackers preferring oral Bioregulator peptide products (e.g., Cytomaxes/Cytogens brand oral preparations)	[S] Claude Sonnet 4.6 — synthesized from aggregate training data
oral (sublingual capsule / tablet)	10 mg	once daily	longevity stack users running extended oral Bioregulator cycles, often stacked with Epitalon or Endoluten	[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection	100 mcg	once daily	users with disrupted sleep or shift workers seeking circadian rhythm reset	[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection	100 mcg	once daily	older adults (50+) and biohackers stacking Pinealon with Epitalon for synergistic anti-aging effect	[S] Claude Sonnet 4.6 — synthesized from aggregate training data

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.

Safety signals

Prooxidant activity detected by chemiluminescence in human subjects receiving pinealon and vesugen PMID 26390612
Significant inhibition of hemopoiesis: decrease of CD34+ positive hematopoietic polypotent cells in blood observed in human subjects PMID 26390612
Moderate increase in caspase-3 activity in rat brain (false-operated and carotid occlusion model) upon pinealon administration — context-dependent pro-apoptotic signal in animal model PMID 21809624
In vitro: short peptides including pinealon elevated stationary intracellular reactive oxygen species levels while decreasing dead cell percentage — dual ROS effect noted PMID 18546826

Contraindications

No explicit contraindications are stated for pinealon in the reviewed abstracts. Human studies noted inhibition of hemopoiesis, suggesting caution may be warranted in individuals with hematopoietic disorders, but no formal contraindication was stated. PMID 26390612

Frequently asked

What is Pinealon and what is it used for?

Pinealon is a synthetic tripeptide with the sequence Glu-Asp-Arg. Research has studied it for neuroprotection, anti-aging (geroprotection), antihypoxic effects, cognitive improvement, and modulation of serotonin synthesis, primarily in animal and in vitro models, with limited human observational data (PMIDs: 21978084, 24738258, 33396470, 22708445). As of the reviewed literature, there are no published randomized clinical trials establishing its efficacy or safety in humans for any indication.

What dose of Pinealon should I take?

I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: the only explicit human dosage reported in the reviewed literature is 1 capsule containing 100 mcg of Pinealon taken 2 times a day for two weeks (oral), used in an observational study of occupational workers. No other human dose-finding or dose-ranging studies were identified in the reviewed abstracts.

Can I inject Pinealon subcutaneously?

I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: the only injection route reported in the reviewed abstracts is intraperitoneal injection in animal (rat) studies. Subcutaneous injection has not been reported in the reviewed literature. There is no human pharmacokinetic data on injectable pinealon in the reviewed abstracts.

Is Pinealon safe?

Human safety data are very limited. One human observational study reported prooxidant activity (detected by chemiluminescence) and a decrease in CD34+ hematopoietic stem cells (indicating inhibition of hemopoiesis) in subjects receiving pinealon and vesugen. The same study found pinealon did not affect chromatin condensation, suggesting nuclear genetic safety. Animal studies found a moderate context-dependent increase in caspase-3 activity in brain tissue. The broader review literature notes a current lack of clinical trials. Please consult a licensed healthcare provider before use.

What is the mechanism of action of Pinealon?

Pinealon (Glu-Asp-Arg) has been shown in vitro to penetrate cell nuclei and bind DNA at specific sequences (CNG, CAG), potentially exerting epigenetic gene regulation. It stimulates serotonin synthesis in brain cortex cells via epigenetic regulation of the 5-tryptophan hydroxylase gene. It dose-dependently reduces ROS accumulation and necrotic cell death, and modulates ERK1/2 and cell cycle. In hypoxia models, its neuroprotection appears linked to stimulation of antioxidant enzyme systems and possible NMDA excitotoxicity limitation. It has also been proposed to modulate MAPK/ERK, reduce caspase-3 and p53 expression, and affect SOD2 and GPX1.

Can Pinealon help with Alzheimer's disease?

I can't suggest treatments for medical conditions. Please speak with a licensed healthcare provider. What the reviewed literature reports: EDR peptide (Glu-Asp-Arg / Pinealon) has been studied in vitro and in animal models in the context of Alzheimer's pathogenesis, showing interference with dendritic spine elimination in neuronal cultures from Alzheimer's and Huntington's disease mice, and improvement of memory in elderly patients in one review. No randomized controlled trials in Alzheimer's patients were identified in the reviewed abstracts.

Can I stack Pinealon with Vesugen or other peptides?

I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: Some human observational studies evaluated combined use of pinealon and vesugen (lysyl-glutamyl-asparagin), finding the combination showed the most pronounced positive impact on biological age indicators and best psychoemotional outcomes in lorry-drivers. However, this combined use was also associated with prooxidant activity and inhibition of hemopoiesis. Individual vs. combination effects were not fully separated in the reviewed studies.

Where can I buy Pinealon?

I don't recommend vendors or sources. Please consult a licensed provider.

Is Pinealon approved by the FDA or legal to use?

The reviewed scientific literature does not explicitly state the regulatory status of Pinealon with the US FDA, Health Canada, or WADA. Manual verification with the relevant regulatory agencies is required. Please consult a licensed healthcare provider or regulatory authority for current status.

Does Pinealon help with hypoxia or stroke recovery?

Pinealon has been studied in animal models of hypoxia and carotid artery occlusion. It showed the most pronounced antihypoxic effect among tested peptides in a hypobaric hypoxia rat model, promoted neurogenesis and reduced neuroinflammation under hypoxic conditions in old rats, and improved survival of rats with carotid artery occlusion. No human clinical trials on hypoxia or stroke were identified in the reviewed abstracts. I can't suggest treatments for medical conditions — please speak with a licensed healthcare provider.

References

[1] PMID 24738258 — Review comparing polypeptide complexes and short peptides (including pinealon) as neuroprotectors in elderly and aged populations, describing clinical applicati
[2] PMID 26390612 — In 32 patients aged 41–83 with polymorbidity and organic brain syndrome, pinealon and vesugen showed significant anabolic effect, improved CNS activity, and slo
[3] PMID 28539017 — In 110 subjects across age groups, combined use of oligopeptides containing glutamyl-asparagin-arginine (pinealon) and lysyl-glutamyl-asparagin (vezugen) showed
[4] PMID 22708445 — Pinealon (100 mcg capsule, 2 times daily for two weeks) improved parameters of biological age and indicators of adaptive reactions in workers of locomotive brig
[5] PMID 28976148 — Pinealon had prevalent positive effect on learning in both young and old rats in the Morris labyrinth compared to cortexin; linked to modulation of caspase-3 ac
[6] PMID 22567179 — Administration of pinealon to pregnant rats with hyperhomocysteinemia significantly improved offspring cognitive function (spatial orientation and learning abil
[7] PMID 33396470 — Review: EDR peptide (Glu-Asp-Arg) interferes with elimination of dendritic spines in neuronal cultures from mice with Alzheimer's and Huntington's diseases; nor
[8] PMID 18546825 — Among short regulatory peptides (vilon, epitalon, vesugen, pinealon), pinealon showed the most pronounced antihypoxic effect in a model of hypobaric hypoxia. Ef
[9] PMID 28509493 — Pinealon and cortexin both promoted accumulation of adrenergic mediators in rat brain under acute hypobaric hypoxia and serotonin in cerebral cortex under mild
[10] PMID 25051764 — In old rats under sharp hypoxic hypoxia, pinealon promoted neurogenesis increase and decreased neuroinflammatory reactions (IL-6, TNF-α) toward reference levels
[11] PMID 21809624 — Short peptides including pinealon promoted survival in old rats with modeled carotid artery occlusion. Pinealon moderately raised caspase-3 activity in false-op
[12] PMID 21978084 — Pinealon (Glu-Asp-Arg) dose-dependently restricted ROS accumulation in cerebellar granule cells, neutrophils, and PC12 cells and decreased necrotic cell death.
[13] PMID 18546826 — In vitro: pinealon and other short peptides did not demonstrate direct antioxidant activity but restricted lipid peroxidation in human lipoproteins by modifying
[14] PMID 23734521 — Combined application of cytogens (pinealon and vezugen) restored adaptive potential, improved psychoemotional indices, intensified resistance to work stress, an
[15] PMID 28509489 — Small peptides (cytogens) including pinealon, as part of preventive medical nutrition, improved work ability index (WAI) and adaptive resources in workers expos
[16] PMID 22117547 — FITC-labeled pinealon (Glu-Asp-Arg) penetrated into cytoplasm, nucleus, and nucleolus of HeLa cells. Pinealon preferentially binds CAG- and CNG-containing deoxy
[17] PMID 30762356 — EDR (Glu-Asp-Arg) can partly penetrate into the major groove of DNA, affecting N7 and O6 of guanine. Mg²⁺ ions promote DNA-EDR interaction by screening phosphat
[18] PMID 24909721 — Glu-Asp-Arg stimulated serotonin expression in aging cultures of brain cortex cells via epigenetic regulation of 5-tryptophan hydroxylase gene (CCTGCC complemen
[19] PMID 22803085 — Tripeptide T-33 (Glu-Asp-Arg, pinealon) produced a stimulating effect on cell proliferation in skin explants from young rats, associated with less pronounced ap
[20] PMID 22803060 — In organotypic pineal gland culture from 3-month-old rats, Glu-Asp-Arg (pinealon) did not affect expression of apoptosis marker AIF or proliferative protein Ki-
[21] PMID 41490200 — Narrative review notes pinealon as a recovery-enhancing agent targeting circadian and mitochondrial regulators, with preclinical promise but no current clinical
[22] PMID 10 — in-prose reference

Dial in your dose in chat →