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Brain & Cognitive

Semax

ACTH(4-7) analog + Pro-Gly-Pro

The cognitive accelerator.

Half-life

~ short (intranasal delivery)

Mol. weight

813.9 g/mol

Sequence

Met-Glu-His-Phe-Pro-Gly-Pro

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Overview

A synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the ACTH(4-7) fragment of adrenocorticotropic hormone, developed and approved in Russia for stroke recovery, transient ischemia, and cognitive disorders. It retains ACTH's central nervous system activity without triggering adrenal cortisol signaling, and is best known for upregulating brain-derived neurotrophic factor (BDNF).

Mechanism of action

Semax's most-documented mechanism is upregulation of brain-derived neurotrophic factor (BDNF) and sensitization of its TrkB receptor. A single intranasal dose in preclinical study produced a ~1.4-fold increase in BDNF protein, ~1.6-fold increase in TrkB phosphorylation, and ~3-fold increase in BDNF mRNA in the hippocampus — the region central to learning and memory consolidation. Semax also modulates dopaminergic and serotonergic signaling and influences monoamine metabolism, which underlies its pro-cognitive, attention-enhancing profile. Importantly, it preserves CNS activity while shedding the adrenal hormonal signaling of full ACTH.

Researched benefits

  • Upregulates BDNF and TrkB (hippocampal neuroplasticity)
  • Modulates dopamine and serotonin systems
  • Approved in Russia for stroke recovery and cognitive disorders
  • Does not trigger adrenal cortisol signaling

Considerations

  • Clinical evidence largely from Russian institutions, not replicated in large Western trials
  • Not FDA-approved
  • Strictly research context outside approved regions

Key Academic Literature & Studies

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Peer-reviewed citations and clinical trials evaluating Semax in scientific literature.

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