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Semax

Semax: A Synthetic ACTH(4–10) Analogue Studied for Neuroprotection

Research summary. Semax is a synthetic heptapeptide developed at the Institute of Molecular Genetics in Russia, structurally based on residues 4–10 of adrenocorticotropic hormone (ACTH) with a C-terminal Pro-Gly-Pro extension to extend stability. It is included on the Russian Vital and Essential Drugs list and has been used clinically in Russia for cerebrovascular indications including ischaemic stroke. Semax is studied for neuroprotective, nootropic, and BDNF-modulating effects, and shares structural-strategic similarities with Selank (also a Russian-developed Pro-Gly-Pro-extended peptide). It is not approved by the FDA or EMA.

Molecular profile

  • Sequence: Met-Glu-His-Phe-Pro-Gly-Pro
  • Molecular formula: C₃₇H₅₁N₉O₁₀
  • Molecular weight: ~813.9 g/mol
  • Class: Synthetic ACTH(4–10) analogue
  • Synonyms: ACTH(4–10) Pro-Gly-Pro; MEHFPGP
  • Common formulation: Intranasal solution (used in clinical practice in Russia)

Mechanism of action

Semax is reported to act through a combination of mechanisms, none of which involve canonical melanocortin or HPA-axis activation:

  • BDNF and NGF upregulation. Reported across rat brain studies, with increased expression and protein levels of brain-derived neurotrophic factor and nerve growth factor in hippocampus and cortex following administration.
  • Gene-expression modulation. Single intranasal administration in rats has been reported to alter expression of multiple genes in the hippocampus and frontal cortex within 20 minutes, including genes involved in vascular function, neuroplasticity, and neuroinflammation.
  • No HPA-axis activation. Unlike full-length ACTH, the truncated Semax sequence does not engage MC2R and does not stimulate cortisol release, despite the structural lineage.
  • Effects on enkephalin metabolism. Semax has been reported to inhibit enkephalinase, prolonging endogenous enkephalin half-life in a manner mechanistically similar to Selank.

The reported activity profile centres on neuroprotection, support of neuroplasticity, and modulation of attention and stress-response systems.

Preclinical and clinical research highlights

Acute ischaemic stroke. Russian clinical research has reported that intranasal Semax administered in the acute stroke window is associated with improved neurological recovery endpoints relative to standard care, supporting its inclusion in Russian stroke management.

Cerebral vascular gene expression. Rodent middle-cerebral-artery-occlusion models have reported that Semax administration modulates expression of approximately 20+ genes related to angiogenesis, vascular smooth muscle function, and erythropoiesis in cortex and spinal cord.

Cognitive endpoints. Healthy rat studies have reported gene-expression changes in hippocampus and frontal cortex within 20 minutes of single intranasal administration, with downstream behavioural endpoints supporting reported nootropic effects.

Default-mode-network activity. Functional MRI work in human research subjects has reported that Semax modulates default-mode-network activity, interpreted as enhanced environmental attention and faster transition from rest to task-focused states.

Attention-deficit research. Russian research has explored Semax in attention-deficit indications in paediatric populations, with reported improvements on attention endpoints.

Limitations of the evidence base

  • The published Semax literature is concentrated almost entirely in Russian research groups, with limited independent Western replication.
  • Western regulatory approval is absent, and the clinical evidence base does not currently meet FDA or EMA standards for stroke or attention-deficit indications.
  • Mechanistic claims regarding the specific molecular targets responsible for the reported gene-expression effects are incompletely characterised.

Current research status

Semax is not approved by the FDA or EMA. It is approved as a prescription medication in Russia. Research-grade Semax is supplied for laboratory use only.

For research-supplier contexts, Semax is supplied as a research-grade investigational peptide and is not intended for self-administration.

Key takeaways for researchers

  • Semax is a synthetic heptapeptide ACTH(4–10) analogue with a Pro-Gly-Pro stability-extension developed in Russia.
  • Reported mechanisms include BDNF/NGF upregulation, gene-expression modulation in hippocampus and cortex, and enkephalinase inhibition; HPA-axis activation is reportedly absent.
  • Reported preclinical and Russian clinical research includes ischaemic-stroke recovery, cerebral vascular gene-expression effects, cognitive endpoints, and attention-deficit applications.
  • Semax is approved in Russia but is not FDA- or EMA-approved.
  • The published literature is concentrated in the originating Russian research programme; independent Western replication is limited.

References

  1. Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV. Effect of semax and its C-terminal fragment Pro-Gly-Pro on the expression of VEGF family genes and their receptors in experimental focal ischemia of the rat brain. J Mol Neurosci. 2013;49(2):328–333.
  2. Kaplan AYa, Kochetova AG, Nezavibathko VN, Rjasina TV, Ashmarin IP. Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neurosci Res Commun. 1996;19(2):115–123.

This article is provided for educational and research purposes only. Semax is a research peptide and is not an approved drug or therapeutic agent in the United States or European Union. It is not intended for human consumption, diagnosis, treatment, cure, or prevention of any disease or condition. All work involving this peptide should be conducted by qualified personnel within an appropriate research setting and in compliance with applicable institutional and regulatory requirements.

Semax | BonesLabs