Pepacorn
← Compounds

Semax

peptide · headlineResearch use only

Modulates neurotransmitter levels by increasing dopamine and serotonin availability

Overview

Semax is a synthetic ACTH-derived neuropeptide used for its cognitive-enhancing, neuroprotective, and antidepressant effects. Developed in Russia, it modulates neurotransmitters and neurotrophic factors like BDNF. It is used in cognitive decline, stress recovery, stroke rehabilitation, and neuropsychiatric disorders in both animal models and limited human trials.

How it works

  • Modulates neurotransmitter levels by increasing dopamine and serotonin availability
  • Upregulates BDNF (brain-derived neurotrophic factor), enhancing synaptic plasticity
  • Exerts antioxidant effects, reducing oxidative stress and neuroinflammation
  • Influences melanocortin receptors involved in cognition, emotion, and immune modulation

Dosing

0.1 mg intranasally 2–3 times daily for 10–14 days per cycle. Repeatable as needed with breaks.

Intranasal0.1 mg standardrange 0.050.2 mg· 2-3 times daily

Caution: In Russian clinical use, doses of 300–600 μg intranasally are reported. These regimens are not approved or validated in the U.S. or other regions without regulatory approval.

Cycling

  • Used 2–3 times daily for 10–14 days. Repeat cycles every 1–3 months based on cognitive or stress recovery goals.

Side effects

Common
  • Headache, restlessness, slight BP fluctuations

Stacking & combinations

With

N-Acetyl Selank Amidate

Benefit

Works synergistically with Selank for anxiolytic and cognitive stability

With

PACAP

Benefit

Boosts neurotrophic and anti-inflammatory effects when paired with PACAP

With

Cortexin

Benefit

Complements Cortexin in neurodegenerative and stroke recovery protocols

Lifestyle support

Diet

Balanced diet rich in antioxidants.

Sleep

Quality sleep. Stress management.

Timing

Morning intranasal dosing for focus throughout the day.

Exercise

Regular mental stimulation and exercise.

Research studies

Studies summarized for educational purposes only. Inclusion does not imply human use; referenced research was conducted in vitro, in animal models, or in regulated clinical trials.

Research study

Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action

Shadrina M, Kolomin T, Agapova T, Agniullin Y, Shram S, Slominsky P, Lymborska S, Myasoedov N. J Mol Neurosci. 2010 May;41(1):30–35. View source ↗

Scientific findings

This in vivo study in male Wistar rats characterized the time-course of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in three central nervous system regions — hippocampus, frontal cortex, and retina — at 20 min, 40 min, 90 min, 3 h, 8 h, and 24 h after Semax administration. Expression levels were quantified by real-time PCR. The authors reported multidirectional, region- and time-dependent modulation of both neurotrophin genes: a transient decrease in hippocampal and retinal NGF/BDNF mRNA at 20 min, an increase in frontal cortex at the same early time point, and a significant rise in retinal BDNF expression by 90 min. These data were interpreted as evidence that Semax engages the neurotrophin system through coordinated regional transcriptional dynamics rather than a single uniform upregulation.

Plain English

Researchers gave Semax to rats and measured the activity of two genes — NGF and BDNF — that produce proteins which help brain cells survive and form new connections. They looked at three brain-related regions (the memory center, the front of the brain, and the retina) at several time points. They found that Semax did not simply turn these genes "up" everywhere — instead, it shifted their activity in different directions in different regions at different times. The pattern is consistent with Semax acting as a regional signal that retunes neurotrophin production rather than a blanket booster.

Research study

Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents

Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grieb P, Rayevsky KS. Neurochem Res. 2005 Dec;30(12):1493–1500. View source ↗

Scientific findings

This rodent study examined Semax's effect on central monoaminergic systems. Using microdialysis and tissue measurements, the authors reported that Semax administration was associated with positive modulation of the striatal serotonergic system and an enhanced striatal release of dopamine, as well as potentiation of locomotor behavior elicited by D-amphetamine. The findings linked Semax's previously documented nootropic profile to measurable changes in dopaminergic and serotonergic neurotransmission, providing a mechanistic bridge between the peptide's structural derivation from ACTH(4-10) and its observed behavioral effects in rodent models.

Plain English

Scientists looked at what Semax does to two of the brain's main chemical messenger systems — dopamine and serotonin — in rats and mice. They found that Semax increased the release of dopamine in a brain region called the striatum and boosted serotonin signaling there as well. When they gave the animals amphetamine (which itself increases dopamine), Semax made the movement-related response stronger. This suggests Semax doesn't act on a single isolated target — it tunes several of the brain's chemical signaling systems at once.

Verified citations

2 · PubMed-checked
  • Semax peptide targets the mu opioid receptor gene to promote recovery after spinal cord injury.mechanismPMID 40692165
  • The peptide semax affects immune and vascular gene expression in rat brain focal ischemia.preclinicalPMID 24661604

Reconstitution

Not applicable — this compound is intranasal. No vial reconstitution needed.

Refrigerate at 2–8°C

Chemistry & PK

Sequence
Met-Glu-His-Phe-Pro-Gly-Pro
Half Life
Likely short (minutes in plasma); CNS effects persist longer due to gene regulation
Degradation
Metabolized by tissue peptidases
Molecular Weight
813.93
Molecular Formula
C37H51N9O10S
Tissue Specificity
Primarily acts in the brain: hippocampus, cortex, hypothalamus

Bioavailability

In
High CNS bioavailability via olfactory and trigeminal nerve transport
Oral
Very poor due to enzymatic degradation in the GI tract
Subq
Not commonly used; intranasal route preferred for CNS targeting

Storage & handling

Lyophilized

Freeze until mixing (−20°C)

Reconstituted

Refrigerate at 2–8°C

Legal / compounding

Research use only
EU
Not Approved
FDA
Not Approved
Canada
Not Approved
Australia
Not Approved

Legal status is a hard gate: non-compoundable or delisted agents cannot be filled and are blocked from protocol export. Keep 503A status current.