A reading of a largely Russian-language literature: what the gene-expression and clinical reports measured, and how far they reach.
In short
- Semax is a synthetic heptapeptide — the ACTH(4-7) fragment extended by a C-terminal Pro-Gly-Pro — described in the literature as an analogue of ACTH(4-10).
- Selank is a synthetic heptapeptide built on the immunopeptide tuftsin, likewise extended by Pro-Gly-Pro, and appears in the early pharmacology under the designation TP-7.
- In rat brain, investigators reported that Semax changed the expression of BDNF and its receptor trkB (Dolotov and colleagues) and of other neurotrophin genes after experimental ischemia.
- Selank was reported to alter the expression of GABAergic-system genes in rat tissue (Volkova and colleagues); the clinical reports in anxiety are small and mostly open-label.
Two peptides, two parent molecules
Both compounds were designed in Russian institutes from endogenous fragments, and both share the same stabilising trick. Semax takes the ACTH(4-7) sequence — Met-Glu-His-Phe — and caps it with a C-terminal Pro-Gly-Pro, a tripeptide that resists the exopeptidases that would otherwise clear a short linear peptide in minutes. The published papers describe it as an analogue of ACTH(4-10), the melanocortin fragment, deliberately shorn of the parts that drive classical steroidogenic activity.
Selank is built the same way on a different parent. Its core is tuftsin, Thr-Lys-Pro-Arg, a tetrapeptide from the immunoglobulin heavy chain, again extended by Pro-Gly-Pro. Much of the foundational pharmacology refers to it, and to related tuftsin analogues, as TP-7: Czabak-Garbacz and colleagues reported in Pharmacological Reports in 2006 on long-term treatment with the tuftsin analogue TP-7 and its effect on anxiety-related behaviour and body weight in rats.
The shared Pro-Gly-Pro tail is worth noting because it is pharmacologically active in its own right — several of the brain studies below measured Pro-Gly-Pro alongside the parent peptide.
The neurotrophin experiments
The most cited line of work is on neurotrophin genes. Dolotov and colleagues reported in Brain Research in 2006 that Semax changed the expression of brain-derived neurotrophic factor (BDNF) and its receptor trkB in the rat hippocampus. Agapova and colleagues reported in Neuroscience Letters in 2007 on neurotrophin gene expression in rat brain under the action of Semax.
A second group of studies put the same question in an injury model. Dmitrieva and colleagues reported in Cellular and Molecular Neurobiology in 2010 that Semax and Pro-Gly-Pro activated the transcription of neurotrophins and their receptor genes after experimental cerebral ischemia in rats, and Stavchansky and colleagues reported a related effect in Molecular Biology in 2011 under incomplete global ischemia.
What these establish is a measured change in specific transcripts and proteins in rodent brain tissue. They do not establish a cognitive or clinical outcome — that is a different kind of experiment — and they say nothing about effects in a person.
Selank and the GABA genes
The Selank molecular work points at a different system. Volkova and colleagues reported in Frontiers in Pharmacology in 2016 that Selank administration affected the expression of several genes involved in GABAergic neurotransmission in rat tissue — a transcriptional readout, consistent with the anxiolytic framing the compound has carried since the TP-7 work, but still a measurement of gene expression in an animal rather than a behavioural or clinical result.
Taken together with the Semax neurotrophin studies, the pattern across this literature is that the primary, most reproducible data are molecular and come from rodents.
The clinical reports, and how to read them
There are human reports, and they should be read for exactly what they are. Gusev, Skvortsova and colleagues reported in a Russian neurology journal in 1997 on semax given during the acute period of hemispheric ischemic stroke, in a clinical and electrophysiological study. Zozulia and colleagues reported in 2008 on selank in patients with generalised anxiety disorder and neurasthenia.
These are small studies, largely open-label, published in a single national literature and predating current trial-reporting standards; several of the primary papers are in Russian and indexed on PubMed only in translation. That does not make them fabricated — they are real, locatable records — but it does mean they fall well short of the randomised, blinded, replicated evidence that supports an approved indication. Where the human evidence is thin, the honest thing is to say so.
The limits
Neither Semax nor Selank is an approved drug in the United States. Nothing above describes an effect in a reader or a patient, recommends a use, or gives any administration guidance; the clinical findings are reported strictly as what investigators measured in a named population.
The compound pages in the Neurobiology world name the models behind each claim, and the neuropeptides article covers the wider mood, memory and sleep literature these two peptides sit inside.
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 Research. 2006;1117(1):54–60.
- Agapova TY, Agniullin YV, Shadrina MI, et al.. Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10. Neuroscience Letters. 2007;417(2):201–205.
- Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cellular and Molecular Neurobiology. 2010;30(1):71–79.
- Stavchansky VV, Tvorogova TV, Botsina AY, et al.. The effect of Semax and its C-end peptide PGP on the expression of neurotrophins and their receptors in the rat brain during incomplete global ischemia. Molecular Biology (Moscow). 2011;45(6):1026–1035.
- Volkova A, Shadrina M, Kolomin T, Andreeva L, Limborska S, Myasoedov N. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Frontiers in Pharmacology. 2016;7:31.
- Zozulia AA, Neznamov GG, Siuniakov TS, Kost NV, Gabaeva MV, Sokolov OYu. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2008;108:38–48.
- Gusev EI, Skvortsova VI, Myasoedov NF, et al.. Effectiveness of semax in the acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 1997;97:26–34.
- Czabak-Garbacz R, Cygan B, Wolański L, Kozlovsky I. Influence of long-term treatment with tuftsin analogue TP-7 on the anxiety-phobic states and body weight. Pharmacological Reports. 2006;58(4):562–567.
What this article is, and is not
This is a summary of published research, written for qualified professionals evaluating compounds for laboratory work. Every compound discussed is supplied by strictly for in-vitro and laboratory research use. None is a drug, a dietary supplement, or a cosmetic; none is intended for human or veterinary use; and nothing above is medical advice, a treatment recommendation, or a claim that any compound produces any effect in a person. We publish no dosing or administration guidance of any kind.
