Semax

Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro, developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in the 1980s. The first four residues (Met-Glu-His-Phe) correspond to residues 4–7 of human adrenocorticotropic hormone (ACTH(4-7)); the C-terminal Pro-Gly-Pro extension stabilizes the peptide against proteolytic cleavage and removes ACTH-like steroidogenic activity.

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / Semax](https://peppudex.com/peptides/semax).

Overview

The ACTH(4-10) fragment of the parent hormone retains neurotropic activity without corticotropin activity. Semax's three-residue C-terminal extension was designed to extend plasma half-life from minutes (native ACTH(4-7)) to a window sufficient for intranasal nootropic dosing in animal models. It is registered in the Russian Federation as a research and stroke/cognitive-axis compound. It is not FDA-approved in the United States.

Mechanism

The mechanism is characterized primarily through hippocampal and basal-forebrain rat studies:

• Upregulates BDNF protein and mRNA in the rat hippocampus and basal forebrain after intranasal administration (Dolotov et al., Brain Res 2006; PMID 16996037 · Dolotov et al., J Neurochem 2006; PMID 16635254 · Dolotov et al., Doklady Biol Sci 2003; PMID 14556513)
• Increases TrkB receptor phosphorylation, the canonical signal-transduction event downstream of BDNF
• Modulates serotonin and dopamine turnover in rodent striatum and cortex
• Specific high-affinity binding sites have been identified in rat basal forebrain (Dolotov et al., 2006)

See: BDNF, TrkB_receptor, ACTH.

Evidence

Russian-language preclinical and small-cohort clinical literature is moderately extensive (stroke recovery, optic-nerve atrophy, ADHD-spectrum behavioral readouts). Western-indexed peer-reviewed publications are smaller in number:

• Dolotov et al. (Brain Res 2006; PMID 16996037) reported 1.4–1.6× elevation of BDNF protein and TrkB phosphorylation in rat hippocampus after a single 50 µg/kg intranasal dose.
• Dolotov et al. (J Neurochem 2006; PMID 16635254) identified specific binding sites for tritium-labeled Semax in rat basal-forebrain cell membranes (KD ≈ 2.4 nM).
• No completed Phase 3 trials registered with the FDA or European Medicines Agency.

Dosing literature

Russian clinical literature describes intranasal administration at 200–600 µg per dose, 1–3 times daily, of a 0.1% intranasal solution. This wiki does not recommend any human dose. The compound is supplied as a chemical reference material for in-vitro research.

Storage

Lyophilized: 4 °C 12+ months, –20 °C indefinite. Reconstituted: 2–8 °C, use within 28 days. Hygroscopic — keep vial sealed until use. See Reconstitution.

Regulatory status

• United States. Research use only. Not FDA-approved.
• Russian Federation. Registered as a research and clinical neuropeptide under domestic pharmaceutical authority since 1994.
• WADA. Not currently on the prohibited list.

See also

• Selank · sister Russian-origin heptapeptide
• BDNF · primary downstream target in rat hippocampus
• ACTH · parent hormone
• [Peppudex card · Semax](https://peppudex.com/peptides/semax) · mechanism, evidence grades A-F, FAQs, peer-reviewed sources

References

• Dolotov OV, Karpenko EA, Inozemtseva LS, et al. "Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus." Brain Res. 2006;1117(1):54-60. PMID 16996037.
• Dolotov OV, Karpenko EA, Seredenina TS, et al. "Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain." J Neurochem. 2006;97 Suppl 1:82-6. PMID 16635254.
• Dolotov OV, Seredenina TS, Levitskaya NG, et al. "The heptapeptide SEMAX stimulates BDNF expression in different areas of the rat brain in vivo." Dokl Biol Sci. 2003;391:292-5. PMID 14556513.