Semax 11 mg

Semax is a synthetic heptapeptide, sequence Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues reproduce positions 4 to 7 of adrenocorticotropic hormone (ACTH). The last three are a Pro-Gly-Pro tripeptide at the C-terminus, occupying the positions held by Arg-Trp-Gly in the parent hormone. Because of this construction the literature names the molecule two ways: ACTH(4-7)PGP, and (Pro8, Gly9, Pro10)ACTH(4-10). It carries CAS registry number 80714-61-0 for the free peptide, molecular formula C37H51N9O10S and an average molar mass of 813.9 g/mol. Public identifiers include PubChem CID 9811102 and FDA UNII I5FAL2585H.

The compound originates from the Institute of Molecular Genetics of the Russian Academy of Sciences, and N. F. Myasoedov appears as an author on five of the eight papers cited below. Semax is a registered pharmaceutical product in Russia. It holds no marketing authorisation in Europe or the United States. PowerfullyPeptides supplies it as a laboratory reagent for research purposes only, not for human consumption.

Three physicochemical features are documented in the literature. First, the proline-rich C-terminal extension changes how the molecule is cleaved by peptidases; Zolotarev et al. (2006) used uniformly tritium-labelled peptide with HPLC to map the breakdown routes in the presence of rat plasma membranes and basal forebrain cell cultures, reporting loss of the N-terminal Met-Glu and the C-terminal Gly-Pro with accumulation of pentapeptide products, and different fragment patterns between glial and neuronal cultures. Second, the single methionine at position 1 carries a thioether sulfur, a group that oxidises on exposure to air and moisture, which is the usual reason lyophilised material of this class is kept sealed and cold. Third, the peptide binds copper(II): Tabbi et al. (2015) resolved three complex species by potentiometry and electron spin resonance spectroscopy, the species predominating from pH 5 upward showing a 4N planar coordination mode. Supplied material is a white lyophilised powder that dissolves in aqueous buffer.

The earliest mechanistic work looked at neurotrophin transcription in cell culture. Shadrina et al. (2001) treated glial cells taken from the basal forebrain of newborn rats and measured mRNA levels; the largest change was recorded 30 minutes after application, with BDNF mRNA reported as increased eight-fold and NGF mRNA five-fold relative to untreated control (Neurosci Lett 308:115-118).

Two 2006 papers from the same group moved this in vivo and asked whether a binding site exists. Dolotov et al. (J Neurochem 97 Suppl 1:82-86) incubated tritium-labelled Semax with cell membranes from rat basal forebrain and reported binding that was time dependent, specific, reversible and dependent on calcium ions, with a dissociation constant of 2.4 plus or minus 1.0 nM and a Bmax of 33.5 plus or minus 7.9 fmol per mg protein. In the same rats, intranasal application at 50 and 250 micrograms per kg bodyweight was followed by a rise in BDNF levels at 3 hours in the basal forebrain but not in the cerebellum. The companion paper (Brain Res 1117:54-60) examined the rat hippocampus after a single application at 50 micrograms per kg body weight and reported a maximal 1.4-fold increase in BDNF protein, a 1.6-fold increase in trkB tyrosine phosphorylation, a 3-fold increase in exon III BDNF mRNA and a 2-fold increase in trkB mRNA, alongside a distinct increase in the number of conditioned avoidance reactions in the treated animals. Both figures are rodent quantities recorded by those authors in rats. They are not directions for use.

A separate line of work is chemical rather than neurobiological. Tabbi et al. (2015) used potentiometry and electron spin resonance spectroscopy to characterise copper(II) binding. Three complex species were resolved, two of them co-existing with a third across the pH range 3.6 to 5, with that third species becoming predominant from pH 5 upward in a 4N planar coordination mode. The same paper reported reduced copper-induced cytotoxicity in the presence of the peptide by MTT assay in SH-SY5Y neuroblastoma and RBE4 endothelial cell lines (J Inorg Biochem 142:39-46).

The largest recent dataset is transcriptomic. Filippenkov et al. (2020) applied RNA-Seq to a rat transient middle cerebral artery occlusion model and identified 394 differentially expressed genes at a threshold of greater than 1.5-fold change, 24 hours after occlusion. The authors describe the direction of change as suppression of genes related to inflammatory processes and activation of genes related to neurotransmission, opposite in sign to the pattern produced by ischaemia-reperfusion alone (Genes 11:681).

The human record is thin by international standards and should be read with that in mind. Gusev et al. (2018) studied 110 patients after ischaemic stroke (43 men, 67 women, mean age 58.0 plus or minus 9.7), split into early (89 plus or minus 9 days) and late (214 plus or minus 22 days) rehabilitation groups with semax and non-semax subgroups; measured endpoints were plasma BDNF, motor performance on the British Medical Research Council scale and the Barthel index. The paper is published in Russian, and the published abstract does not describe randomisation, blinding or placebo control. More broadly, the great majority of Semax publications come from a small number of Russian institutions, many in Russian-language journals, and independent replication outside that group is limited. Work from unaffiliated laboratories has begun to appear: Liu et al. (2025), a Chinese group publishing in the British Journal of Pharmacology, reported functional recovery after spinal cord injury in female C57BL/6 mice and attributed it to the mu opioid receptor gene Oprm1 and downstream deubiquitination. The overall evidence base nonetheless remains narrow, and no adequately powered independent human trial has been published.