Semax: ACTH(4-10) Analogue — Neuroprotection & Cognitive Function
Educational Content Only
The information on this page is based on scientific publications and is for educational purposes only. It does not constitute medical prescription, diagnosis, therapeutic guidance, or recommendation for use. Any clinical intervention must be individualized by a qualified healthcare professional.
⚠️ The information on this page is based on scientific publications and is for educational purposes only. It does not constitute medical prescription, diagnosis, therapeutic guidance, or recommendation for use. Any clinical intervention must be individualized by a qualified healthcare professional.
Scientific analysis of Semax (MEHFPGP): ACTH(4-10) analogue with PGP modification for stability, data from cerebral ischemia studies (tMCAO), BDNF modulation and applications described in literature for ischemic stroke and cognitive function.
Mechanism of Action
Semax is a synthetic heptapeptide of sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), derived from the ACTH(4-7) fragment with the Pro-Gly-Pro tripeptide added at the C-terminus. The PGP addition confers enzymatic resistance, prolonging functional half-life. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences by Myasoedov and colleagues. It acts as a melanocortin analogue without corticotropic activity, with a profile described as neuroprotective and nootropic.
1. ACTH(4-7) derivation without corticotropic activity
The MEHF sequence corresponds to residues 4-7 of ACTH, a region associated with the behavioral activity of the original molecule — without the domains responsible for activating the MC2R receptor in the adrenal. Therefore, Semax does not stimulate cortisol release or other adrenal hormones.
2. BDNF and neurotrophic factor modulation
Preclinical studies in rats describe increased expression of BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor) in the hippocampus and cortex after Semax administration. BDNF activation is associated with hippocampal neurogenesis, synaptic plasticity and neuronal survival.
3. Transcriptome modulation in cerebral ischemia
RNA-Seq analyses in a transient middle cerebral artery occlusion (tMCAO) model in rats, published by Filippenkov et al. (2020), identified 394 differentially expressed genes under Semax action: suppression of pro-inflammatory genes and activation of neurotransmission-related genes.
4. Intranasal administration — CNS bioavailability
In Russian studies, Semax is described in intranasal use. The intranasal route is discussed in the literature as a pathway capable of partially bypassing the blood-brain barrier via olfactory and trigeminal routes, allowing higher relative CNS concentration compared to systemic routes.
- •Heptapeptide derived from ACTH(4-7) with added Pro-Gly-Pro for stability.
- •No corticotropic activity — does not raise cortisol.
- •Modulates BDNF, NGF and gene expression in ischemia response.
- •Approved for clinical use in Russia for ischemic stroke; no FDA/EMA approval.
Applications Described in Literature
Ischemic stroke — neuroprotection described in animal models
Moderate evidencetMCAO rat model studies document reduction of inflammatory markers (MMP-9, JNK) and CREB activation (factor associated with neuronal recovery) after Semax administration. In Russia, the peptide is used clinically as an adjunct in acute ischemic stroke, based on local studies not replicated at scale in Western literature.
Cognitive function and memory — preclinical models
Preliminary evidenceGlazova et al. (2020) describe that Semax reversed learning impairment and anxiety induced by neonatal SSRI (fluvoxamine) exposure in rats, normalizing brain monoamine levels. Other Russian studies document learning improvement in maze and object recognition models.
Immune modulation via neuroimmune crosstalk
Preliminary evidenceMedvedeva et al. (2017) describe that Semax regulates expression of immune genes (interferon, immunoglobulins, cytokines) in rat cerebral cortex after ischemia. The authors propose the neuroprotective mechanism is mediated by neuroimmune signaling rather than direct neuronal action alone.
Relevant Studies
4 curated studies · 2017–2021
Peer-reviewed evidence with PMID verifiable on PubMed
Brain Protein Expression Profile Confirms the Protective Effect of the ACTHPGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion
Sudarkina OY, Filippenkov IB, et al. · International Journal of Molecular Sciences
tMCAO rat model. 24h post-ischemia, Semax increased active CREB in subcortical structures and reduced MMP-9, c-Fos and active JNK — suggesting suppression of inflammation/cell death and activation of recovery pathways.
Novel Insights into the Protective Properties of ACTHPGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats
Filippenkov IB, Stavchansky VV, et al. · Genes (Basel)
RNA-Seq identified 394 differentially expressed genes in Semax-treated rats after tMCAO: suppression of inflammatory genes and activation of neurotransmission genes — inverse pattern to untreated ischemia.
Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats
Glazova NY, Manchenko DM, et al. · Neuropeptides
Neonatal fluvoxamine exposure in rats caused anxiety and learning impairment in young adulthood. Semax reversed anxiety-like behavior, improved learning and normalized brain biogenic amines.
Semax, an analog of ACTH, regulates expression of immune response genes during ischemic brain injury in rats
Medvedeva EV, Dmitrieva VG, et al. · Molecular Genetics and Genomics
Transcriptome analysis showed Semax increases interferon signaling and antigen presentation, while PGP alone attenuates post-ischemic immune activation — suggesting a relevant role for the MEHF fragment.
Latest literature review: 2026-04 · PubMed
FAQ
What is Semax?
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the ACTH(4-7) fragment with an added Pro-Gly-Pro tripeptide for stability. Developed at the Institute of Molecular Genetics (Russian Academy of Sciences), it is described in the literature as a nootropic and neuroprotective peptide.
How does Semax act on the brain?
Transcriptome studies in cerebral ischemia models (tMCAO) show Semax modulates expression of genes involved in immune response, neurotransmission and neurotrophic factors. Publications by Filippenkov et al. (2020) document suppression of inflammatory processes and activation of neurotransmission pathways after ischemia-reperfusion.
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