Selank 10mg Peptide

Selank is a synthetic heptapeptide, Thr-Lys-Pro-Arg-Pro-Gly-Pro, with a molecular weight of 751.9 g/mol and CAS number 129954-34-3. It was designed at the Institute of Molecular Genetics of the Russian Academy of Sciences by taking the endogenous immunomodulatory tetrapeptide tuftsin (Thr-Lys-Pro-Arg, 500.6 g/mol) and extending it at the C-terminus with Pro-Gly-Pro. Tuftsin itself is cleaved by serum peptidases too quickly to be useful as a pharmacological tool. The three added residues, two of them prolines, block that cleavage and give the molecule enough plasma survival to reach the brain.

The research record is unusual in two ways that a reader should know before weighing any of it. First, almost all of it comes from one country and a small number of connected institutes: the Institute of Molecular Genetics, the Zakusov Research Institute of Pharmacology, and the Mental Health Research Center, all in Moscow. Roughly 135 papers are indexed in PubMed, and a large fraction are Russian-language abstracts in Bulletin of Experimental Biology and Medicine or Doklady Biological Sciences. Second, Selank has never been the subject of a study registered on ClinicalTrials.gov. The human data that exist are Russian comparative studies published without a phase designation.

Selank is registered in Russia as a prescription anxiolytic nasal formulation. It holds no marketing authorisation in the United States, Canada, the European Union, the United Kingdom, or Australia, and it is supplied here as a research reagent only.

Selank has no single receptor. The pharmacology reported for it converges on four separable systems: allosteric modulation of GABA binding, inhibition of the enzymes that destroy enkephalins, regulation of BDNF transcript and protein levels in the hippocampus, and an immunological signature inherited from its tuftsin parent. The four are not equally well evidenced, and the GABA account in particular rests on binding and electrophysiology rather than on a demonstrated benzodiazepine-site interaction.

The GABA work is the most direct. Vyunova and colleagues (2018) used radioligand binding on isolated brain cell plasma membranes and found that Selank shifts [3H]GABA binding as a positive allosteric modulator, in a concentration-dependent and receptor-subtype-selective way. The same experiments showed Selank blocking the modulatory activity of diazepam and of olanzapine, which argues that its binding site partially overlaps theirs rather than being identical to either. Povarov and colleagues (2017) applied 1 to 8 micromolar Selank to rat hippocampal slices and recorded an increase in the amplitude and discharge rate of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons, sometimes preceded by a brief decrease. Across that concentration range the effect showed no significant concentration dependence, which is itself a point against a simple orthosteric mechanism.

The transcriptional evidence cuts both ways and is worth stating plainly. Volkova and colleagues (2016) measured 84 neurotransmission genes in rat frontal cortex 1 and 3 hours after 300 micrograms per kilogram of Selank or of GABA, and found 45 genes changed at 1 hour and 22 at 3 hours, with the Selank and GABA profiles positively correlated. But when Filatova and colleagues (2017) ran the same 84-gene panel on IMR-32 human neuroblastoma cells, Selank alone changed nothing. What it did do was suppress almost all of the expression changes GABA produced when the two were applied together. Read together, the two results say Selank is not a transcriptional agonist in its own right: it acts on how GABA engages its receptor, and the gene expression seen in vivo is downstream of that.

The enkephalin arm is the oldest and the most quantitative. Zozulya and colleagues (2001) showed that Selank inhibits enzymatic hydrolysis of plasma enkephalin dose-dependently with an IC50 of 15 micromolar, more potently than the reference peptidase inhibitors bacitracin and puromycin. Zolotarev and colleagues (2004), using leu-enkephalin labelled with tritium at every residue, resolved which enzyme classes are involved: aminopeptidases account for about 80% of total enkephalin-degrading activity in plasma, dipeptidylcarboxypeptidases about 10%, and dipeptidylaminopeptidases about 2%. Selank was found to be specific for the carboxypeptidases and dicarboxypeptidases, which is the opposite selectivity to Semax, whose inhibitory effect on the same system runs through the aminopeptidases.

Tuftsin is a natural tetrapeptide released from the CH2 domain of the IgG heavy chain. Its classical activity is on phagocytes: it promotes phagocytosis by macrophages and microglia through neuropilin-1 and Fc receptor pathways, and it is the reason Selank has an immunological literature at all. Tuftsin's problem as a pharmacological tool is that serum peptidases take it apart almost immediately, which is what the Pro-Gly-Pro extension was designed to fix.

The interesting question is whether the extension only buys time or whether it changes the pharmacology. Semenova and colleagues (2009) answered it directly in a group of 87 mature Wistar rats pretreated with the serotonin synthesis inhibitor p-chlorophenylalanine at 320 mg/kg intraperitoneally four days before the experiment. Selank enhanced 5-HT metabolism in the brain stem 30 minutes after injection. Tuftsin, given the same way, produced no change in brain stem 5-HT metabolism and actually decreased it in the neocortex. The two molecules are not interchangeable, and the three extra residues are doing more than protecting the N-terminal four.

The same group had earlier shown (2010) that a single 300 micrograms per kilogram injection of Selank in Wistar rats, given after the tenth of thirty food-rewarded conditioning trials, activated 5-HT metabolism in the hypothalamus and caudal brain stem for 30 minutes to 2 hours and increased memory trace stability out to 30 days. That is the strongest single piece of evidence that the serotonergic effect is functionally consequential rather than incidental.

The claim readers encounter most often is that Selank works like a benzodiazepine without the sedation and dependence. The mechanistic support for the first half of that sentence is real but narrower than it is usually presented. What has been shown is that Selank behaves as a positive allosteric modulator of [3H]GABA binding on isolated brain cell plasma membranes, in a subtype-selective and concentration-dependent way, and that it blocks the modulatory activity of diazepam and olanzapine when they are present together. Blocking a benzodiazepine's modulation is the behaviour of a molecule whose site partially overlaps the benzodiazepine site, not one that occupies it.

No published study reports Selank displacing a benzodiazepine radioligand such as [3H]flunitrazepam from the benzodiazepine binding pocket, and no crystal or cryo-EM structure of Selank bound to a GABA-A receptor exists. The functional electrophysiology is one paper: an increase in spontaneous inhibitory postsynaptic current amplitude and rate in rat hippocampal CA1 pyramidal neurons at 1 to 8 micromolar, with no significant concentration dependence across that range and, in some cells, a transient decrease first.

The transcriptional experiments add a useful negative. In IMR-32 neuroblastoma cells, Selank on its own changed the mRNA level of none of the 84 GABAergic and neurotransmission genes tested. Combined with GABA, it suppressed almost all of the changes GABA alone produced. Combined with olanzapine, it broadened the set of genes olanzapine altered. Selank behaves in these systems as a modifier of another ligand's signal, which is consistent with an allosteric role and inconsistent with direct receptor activation.

A 2021 pharmacology review of GABA-receptor-acting sedative-hypnotics grouped Selank with phenibut as poorly studied compounds of Russian origin being sold to consumers outside any regulatory framework. That framing is worth carrying alongside the mechanistic papers: the depth of the receptor characterisation does not match the confidence with which the mechanism is usually stated.

The enkephalinase story starts from a clinical observation rather than from the peptide. Zozulya and colleagues (2001) examined patients with anxiety and phobic disorders classified under DSM-IV criteria and found a considerable shortening of enkephalin half-life and reduced total enkephalinase activity in blood specifically in generalised anxiety disorder, and not in panic disorder or agoraphobia. Their interpretation was that patients with generalised anxiety carry low blood concentrations of endogenous enkephalinase inhibitors. Selank was then tested as an exogenous replacement for those missing inhibitors, and it inhibited plasma enkephalin hydrolysis with an IC50 of 15 micromolar.

The animal counterpart is a strain comparison rather than a dose-response. Sokolov and colleagues (2002) found that intact BALB/c and C57BL/6 mice differ significantly in the plasma half-life of leu-enkephalin at baseline. Selank at 100 micrograms per kilogram produced an anxiolytic effect in the open field test and lengthened plasma leu-enkephalin half-life in BALB/c mice, and did neither in C57BL/6. Behaviour and enzymology moved together, in the same strain, which is stronger evidence for the mechanism than either result alone.

This is also the clearest point of separation from Semax. Working with leu-enkephalin labelled with tritium at every amino acid residue, Zolotarev and colleagues resolved the plasma enkephalin-degrading system into its components and found Selank specific for carboxypeptidases and dicarboxypeptidases, while Semax exerts its inhibitory effect on the same system through the aminopeptidases. Two peptides sharing a Pro-Gly-Pro tail, acting on the same downstream mediator through opposite ends of the enzyme cascade.

The reference human study is Zozulia and colleagues (2008), published in Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. Sixty-two patients with generalised anxiety disorder or neurasthenia were studied: 30 received Selank and 32 received the benzodiazepine medazepam. State was assessed on the Hamilton, Zung and CGI scales, and serum enkephalin activity was measured alongside. Anxiolytic effect was similar in the two arms; the Selank arm additionally showed antiasthenic and psychostimulant effects the comparator did not. The biological arm of the study reproduced the 2001 finding in a treatment context: the shortened leu-enkephalin half-life in these patients correlated with disease duration and with symptom severity, and it lengthened under Selank, most clearly in the generalised anxiety subgroup. The paper reports no phase designation, no randomisation or blinding scheme in the indexed abstract, and no trial registration.

A second line of human work treats Selank as an add-on rather than a substitute. Medvedev and colleagues (2015) compared phenazepam monotherapy in 30 patients against phenazepam plus Selank in 40 patients with anxiety-phobic, hypochondriac and somatoform disorders coded F40.2-9, F41.1-9 and F45.0-2. The combination brought the benzodiazepine's effect on the HDRS forward in time and reduced the burden of its characteristic unwanted effects, including attention and memory impairment, sedation, lengthened sleep and emotional indifference, both during co-administration and after the benzodiazepine was withdrawn. Quality of life on the SF-36 was higher in the combination arm.

The most methodologically modern human data are imaging, not clinical. Panikratova and colleagues (2020) ran resting-state fMRI in 52 healthy participants three times each, before injection and at 5 and 20 minutes after, comparing Selank, Semax and placebo. Group and condition differences appeared in functional connectivity between the right amygdala and a right-hemisphere region spanning fusiform, inferior and middle temporal and parahippocampal gyri. Post hoc analysis separated shared from compound-specific effects for the first time. The design is small and acute, but it is the only Selank human study with a placebo arm and an objective endpoint.

Immunologically, Uchakina and colleagues (2008) reported two findings from patients with anxiety-asthenic disorders. In vitro, Selank at 10^-7 M completely suppressed IL-6 gene expression in peripheral blood cells from patients with depression, and did not do so in cells from healthy controls, while paradoxically raising IL-6 concentration in the patient cell cultures. In vivo, patients with generalised anxiety disorder and neurasthenia who received Selank across 14 days showed shifts in serum Th1/Th2 cytokine balance whose dynamics were significantly inversely correlated. Both observations are state-dependent: the effect on the cytokine appears where the cytokine is already dysregulated.

Selank and Semax are siblings by design, not by sequence. Both were built at the Institute of Molecular Genetics by attaching Pro-Gly-Pro to a bioactive parent fragment. For Selank the parent is tuftsin, Thr-Lys-Pro-Arg. For Semax it is the ACTH(4-7) fragment Met-Glu-His-Phe, giving Met-Glu-His-Phe-Pro-Gly-Pro, C37H51N9O10S, 813.9 g/mol. The 62 g/mol difference between the two molecules is not a rounding matter: several comparison pages circulate a figure near 768 g/mol for Semax, which matches neither the sequence nor the PubChem record. Downstream they diverge as well: Semax is characterised through the melanocortin system and BDNF and NGF expression, Selank through GABA binding, enkephalinase inhibition and tuftsin-derived immune signalling, and the two inhibit the plasma enkephalin cascade at opposite ends. This catalogue lists Semax and the combined Selank plus Semax vial separately, and a combined vial cannot support dose-response work on either peptide alone.

N-Acetyl Selank Amidate is the modification buyers ask about most. It is Ac-Thr-Lys-Pro-Arg-Pro-Gly-Pro-NH2: the same heptapeptide with an acetyl group capping the N-terminus and an amide replacing the free C-terminal carboxyl. The chemistry behind it is standard and sound. An N-terminal acetyl group removes the free alpha-amino group that aminopeptidases require, and a C-terminal amide removes the free carboxylate that carboxypeptidases require, so both exopeptidase routes into the molecule are closed. The two modifications add roughly 41 g/mol, putting the amidated analogue near 792.9 g/mol against Selank's 751.9.

What almost no page states is the evidentiary position. There is no PubChem compound record and no CAS registry number for N-Acetyl Selank Amidate, and there is no published study of the amidated analogue itself: not a binding assay, not a behavioural model, not a pharmacokinetic comparison against unmodified Selank. Every claim made for it is extrapolated from Selank on the argument that terminal capping alters stability without altering activity. That argument is reasonable for many peptides and wrong for some, because a capped terminus can also remove a charge the receptor was using. Anyone choosing between the two forms is choosing between a molecule with a hundred-odd papers behind it and a chemically sensible derivative with none.

One further point of confusion is worth resolving. Selank's own resistance to peptidases comes from the Pro-Gly-Pro tail, not from any terminal cap, and that tail is present in both forms. The acetyl and amide groups on the amidated version are a second, independent layer of protection, not the mechanism that made Selank viable in the first place.

Selank is supplied as a lyophilized powder and is hygroscopic in that state. Lyophilized material is held desiccated at -20°C, protected from light, and tolerates ambient temperature for the transit period. Once taken into aqueous solution the peptide should be kept at 2 to 8°C and protected from repeated freeze-thaw cycles, which are more damaging to short peptides than a single extended cold period. Bacteriostatic water is the usual reconstitution medium for multi-use vials; sterile water carries no preservative and gives a much shorter working window.

Three of the seven residues are proline, which has two analytical consequences. Proline-rich peptides show cis-trans isomerisation about the imide bond, and on a reversed-phase HPLC column that can broaden a peak or produce a shoulder that looks like an impurity but is the same molecule in a second conformer. Column temperature is the usual way to collapse it. Prolines also make the peptide resistant to the ordinary exopeptidases, which is the property the design was after.

Identity is confirmed by mass spectrometry against the expected average mass of 751.9 and the formula C33H57N11O9. Purity is normally reported as HPLC area percent, which is not the same number as net peptide content: a vial certified at 99% by HPLC still contains residual water and counterion, so the peptide fraction by weight is typically in the eighties. Peptides purified by reversed-phase chromatography usually arrive as the trifluoroacetate salt unless a salt exchange to acetate has been performed, and residual TFA is cytotoxic to some cell lines at concentrations that do not register on a purity chromatogram. A certificate of analysis that reports HPLC purity, mass confirmation, net peptide content and counterion tells a different and more complete story than one reporting purity alone.

On stability in solution, the published biodegradation work used peptides labelled uniformly with tritium at 50 to 150 Ci/mmol, allowing every hydrolysis product to be tracked at once. In plasma the major products of Selank breakdown are the pentapeptide TKPRP, the tripeptide TKP, and the dipeptides RP and GP. A comparative distribution study of glyprolines given by intraperitoneal, intranasal, intragastric and intravenous routes in rats found the intranasal route optimal for delivering these molecules to the central nervous system, and noted a high affinity of both Selank and Pro-Gly-Pro for gastric tissue regardless of route.

The immunological work follows from the tuftsin ancestry and is mostly transcriptional. Kolomin and colleagues (2011) measured 84 inflammation-related genes in mouse spleen 6 and 24 hours after a single 100 micrograms per kilogram intraperitoneal injection and found 34 changed. Bcl6, a transcriptional repressor central to immune system development, responded to Selank and to each of its fragments, along with Bcl6 target and corepressor genes. A follow-up (2014) tracked the time course more finely and found C3 mRNA down 3-fold as early as 30 minutes, a wave-like pattern in Casp1, and a fall in Xcr1 at 90 minutes. Notably, the dipeptide Gly-Pro reproduced most of the profile on its own, which raises the possibility that part of what is attributed to Selank belongs to its fragments.

In whole-animal stress models the peptide has been tested well outside the brain. Wistar rats given 80, 250 or 750 micrograms per kilogram intraperitoneally 15 minutes before restraint stress showed lower corticosterone and reduced atrophic and inflammatory change in the colon wall compared with stressed controls, along with normalised mast cell counts. In the same laboratory's microbiota work, chronic restraint stress reduced obligate colon flora and expanded opportunistic organisms, and Selank pretreatment restored the balance.

Two ethanol models are worth separating from the anxiety literature because they test a different prediction. In DBA/2 mice, Selank at 0.3 mg/kg intraperitoneally prevented the hyperlocomotion induced by 2.0 g/kg ethanol and blocked the expression of behavioural sensitisation without affecting its formation, matching the profile of the opioid receptor blocker naloxone at 1.0 mg/kg and unlike the sigma-1 agonist afobazole. In naloxone-precipitated morphine withdrawal in outbred rats, a single 0.3 mg/kg injection reduced the total withdrawal index by 39.6% and raised the tactile sensitivity threshold 9-fold. Both results point back to the endogenous opioid system rather than to GABA, and both are consistent with the enkephalinase mechanism.

A 6-hydroxydopamine model of parkinsonism supplies a useful null. Selank and Semax were given to rats with toxic lesions of the substantia nigra; neither peptide affected motor activity or passive defensive behaviour. Selank did reduce anxiety in the maze, the same effect it produces in intact animals, which the authors read as evidence that nigral damage does not alter the response to the peptide. The compound is anxiolytic in that model and nothing more.