Semax
Semax is a synthetic ACTH(4-10) heptapeptide analogue, approved as a nootropic/neuroprotective prescription drug in Russia but not approved by the FDA or EMA, studied mainly in rodents for BDNF/NGF-mediated effects on cognition and ischaemic injury.
MEHFPGP
- Nonpolar5
- Acidic (−)1
- Basic (+)1
- 7 residues
Met-Glu-His-Phe-Pro-Gly-Pro
Semax is a synthetic heptapeptide derived from the ACTH(4-10) fragment of adrenocorticotropic hormone, with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP). The N-terminal ACTH(4-7) portion (Met-Glu-His-Phe) carries the neurotropic activity, while the added C-terminal Pro-Gly-Pro tail is intended to slow enzymatic breakdown and prolong the molecule's action relative to the unmodified fragment. Because it is based on a short ACTH fragment rather than full ACTH, it is designed to retain neurotropic effects without the corticotropic (adrenal steroidogenic) activity of the parent hormone.
In rodent studies, Semax has been reported to upregulate brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and the TrkB receptor in the hippocampus and frontal cortex, and to modulate serotonergic and dopaminergic neurotransmission. Additional proposed mechanisms include interaction with melanocortin receptors (such as MC4 and MC5) and inhibition of enkephalin-degrading enzymes. Its precise receptor pharmacology is not fully established; secondary sources note that its mechanism of action is not completely understood.
As a peptide, Semax has poor oral bioavailability and is typically administered parenterally, most commonly as an intranasal spray or by subcutaneous injection. The parent peptide is reported to be short-lived in plasma (on the order of minutes), undergoing rapid peptidase degradation, although downstream molecular effects (e.g. neurotrophin gene-expression changes) have been described as persisting considerably longer.
Regulatory status: Semax is approved and marketed as a prescription medicine in Russia, where it appears on the Russian List of Vital and Essential Medicines (approved 7 December 2011) and is used for indications such as ischaemic stroke and cognitive disorders. It is not approved by the US FDA or the EMA, is not a scheduled/controlled substance in the US, and in most countries outside Russia it is unlicensed and sold only as a research chemical. This entry is informational and does not constitute therapeutic, dosing, or medical advice.
Semax is a synthetic heptapeptide analogue of the ACTH(4-10) fragment in which the C-terminus is extended with a Pro-Gly-Pro tail to slow enzymatic degradation, so it retains neurotropic activity associated with ACTH without its corticotropic (steroidogenic) effect. In animal models it has been reported to upregulate expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and the TrkB receptor in the hippocampus and frontal cortex, and to modulate serotonergic and dopaminergic signalling. It may also interact with melanocortin receptors (e.g. MC4/MC5) and inhibit enzymes that degrade enkephalins. Its precise receptor pharmacology is not fully established and is described in the literature as not yet fully characterised.
- Human evidence
- Preclinical (rodent) studies plus clinical use in Russia/neighbouring states; minimal independent or Western trial data
- Regulatory status
- Approved and marketed as a prescription medicine in Russia (and used in some neighbouring states), where it has been on the Russian List of Vital and Essential Medicines (approved by the Russian government on 7 December 2011) for indications including ischaemic stroke and cognitive disorders. NOT approved by the US FDA or the EMA; in most other countries it has not been evaluated, approved, or marketed and is sold only as a research chemical. Not a controlled/scheduled substance in the US.
- Investigated in preclinical (rodent) models as a neuroprotective agent in cerebral ischaemia/stroke, where it has been reported to activate transcription of neurotrophins and their receptors in ischaemic cortex (PMC11498467, Cell Mol Neurobiol 2009).
- Studied as a nootropic candidate for effects on learning, memory and attention via BDNF/NGF-mediated neuroplasticity in rodents.
- Used as a research tool to probe ACTH/melanocortin-fragment signalling and serotonergic/dopaminergic modulation in the brain (Neurochem Res, 2005).
- Examined for effects on neurotrophin gene-expression dynamics across hippocampus, frontal cortex, and retina.
- Outside Russia there are no Western regulatory safety reviews (FDA/EMA), so the long-term safety profile in humans is not established by independent authorities.
- Most mechanistic and efficacy data come from rodent studies; large, independent, placebo-controlled human trials are lacking (PubMed / PMC literature).
- Material sold as 'research-grade' Semax is not manufactured to pharmaceutical standards and may vary in purity, identity, and sterility.
- As an ACTH(4-10) fragment analogue it is designed to lack adrenal steroidogenic activity, but its full off-target receptor activity is incompletely characterised, and Wikipedia notes its mechanism of action is not fully known.
- [1]PubChem Compound 9811102: Semax (ACTH (4-7), Pro-Gly-Pro-)PubChem
- [2]Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia (original research, Cell Mol Neurobiol 2009)PMC
- [3]Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents (Neurochem Res, 2005)PubMed
- [4]Semax — overview, structure, and regulatory statusWikipedia