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Research Memos

Semax vs Selank

Semax and Selank are different seven-residue peptides with a shared Pro-Gly-Pro ending. Their patient studies addressed different conditions: stroke-related deficits for Semax and anxiety-related symptoms for Selank. A small study included both compounds and placebo in healthy participants, but measured brain-scan connectivity rather than clinical benefit. These sources cannot rank them as treatments for anxiety, cognition or stroke.

Research reviewed October 15, 2026. Educational information only.

Two sequences with a shared ending

Semax has the sequence Met-Glu-His-Phe-Pro-Gly-Pro. It combines the ACTH(4–7) sequence with a Pro-Gly-Pro ending. Selank has the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro and is derived from the tuftsin sequence. Sharing the final three residues does not make the compounds identical; their first four residues are different.

The study preparations also matter. Acetylating Semax at its starting amino group changed copper binding and removed protection against copper toxicity in a nerve-like cell line in Magrì and colleagues’ 2016 experiments. An acetate salt and an N-terminal acetyl modification describe different chemical changes. Results for the original peptide cannot establish equivalent effects for a modified derivative.

The main differences

What distinguishes the molecules and their biological research?

The original peptides have seven residues. A shared Pro-Gly-Pro ending is a sequence feature, not evidence that they have the same targets or clinical effects.

Semax

Semax is Met-Glu-His-Phe-Pro-Gly-Pro. In rat hippocampus, a memory-related brain region, it increased BDNF, a protein supporting nerve cells, and activation of BDNF’s TrkB receptor. Treated rats also made more learned avoidance responses. These measurements do not establish cognitive enhancement in people.

Sources

Selank

Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro. In IMR-32 tumor-derived cells, Selank alone did not produce an established change in the measured RNA messages used to make proteins. Adding it with GABA, an inhibitory neurotransmitter, or olanzapine changed the other substance’s response pattern.

Sources

What did the patient studies actually report?

These reports enrolled different diagnoses and used different active or conventional-treatment controls; they did not assign patients between Semax and Selank.

Semax

In an acute-stroke report,30 patients receiving Semax plus intensive care were compared with 80 receiving conventional care for strokes of similar severity and location. Neurological deficits, especially movement problems, reportedly decreased faster. The abstract does not give an effect size, interval or documented randomization/blinding.

Sources

Selank

In 62 patients with generalized anxiety disorder or neurasthenia,30 received Selank and 32 medazepam. Anxiety ratings reportedly improved similarly, and additional anti-fatigue/activating effects were described with Selank. Without a numerical difference or interval, the abstract cannot establish equal efficacy.

Sources

Was either compound compared in the same human experiment?

Panikratova and colleagues randomly assigned 52 healthy participants to intranasal Semax (14), Selank (16) or placebo containing 0.1% nipagin (22). Scans before administration and 5 and 20 minutes afterward measured coordinated fluctuations of right-amygdala and right-temporal brain activity. These are imaging measurements, not clinical symptom outcomes.

Semax

From 5 to 20 minutes, coordinated brain activity increased more with Semax than placebo in a post hoc analysis (adjusted P<0.05); from baseline to 5 minutes, it decreased relative to placebo. The authors described a larger later increase than with Selank, but doses differed and the peptide groups already differed at baseline. The small study did not establish a clinical advantage.

Sources

Selank

From 5 to 20 minutes, coordinated activity increased more with Selank than placebo in the post hoc analysis (adjusted P<0.05). The baseline-to-5-minute comparison did not establish a Selank change against placebo. Different doses, small groups and a pre-existing group difference limit comparison with Semax; anxiety improvement was not demonstrated.

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What do the exposure and derivative studies establish?

Tracer breakdown studies identify the parent and its fragments in experimental preparations. A chemical modification can also change biological behavior, so a salt or modified derivative needs its own specification.

Semax

In nerve-cell preparations, Semax yielded HFPGP and PGP fragments. In a separate cultured nerve-like cell experiment, the original Semax protected cells against copper toxicity while an N-acetylated form did not. These experiments provide no established human brain half-life or clinical equivalence between derivatives.

Sources

Selank

Tracer work identified TKPRP, TKP, RP and GP among Selank’s breakdown products in plasma. The public abstract gives no numerical human elimination curve. FDA’s separate Selank acetate entry concerns that named compounded substance and does not establish the exposure of every derivative.

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Can the available safety evidence rank them?

Small symptom studies and experimental mechanisms cannot quantify uncommon harms or compare long-term safety between these compounds. FDA’s documents concern specified bulk substances and proposed compounding uses.

Semax

FDA raises potential immune-reaction risks from aggregation and peptide impurities and inadequate safety information for proposed routes. Its July 2026 briefing also finds insufficient effectiveness evidence for specified proposed uses; the briefing is not a final regulatory determination.

Sources

Selank

FDA’s Selank acetate row raises potential immune-reaction risks associated with aggregation and impurities and says important human safety information is lacking. This does not establish that Selank is safer than Semax or that a modified Selank preparation shares a tested safety profile.

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The patient studies treated different conditions

Gusev and colleagues (1997) studied 30 people receiving Semax alongside intensive treatment for an acute hemispheric ischemic stroke, a stroke caused by blocked blood supply. They compared these patients with 80 receiving conventional treatment whose strokes had similar severity and locations. The authors reported faster reduction of neurological deficits, especially movement problems, with added Semax. The public abstract does not document random allocation or blinding and gives no numerical treatment difference or interval.

Zozulia and colleagues (2008) compared Selank in 30 people with medazepam in 32 people with generalized anxiety disorder or neurasthenia, a diagnosis involving fatigue and related symptoms. Anxiety ratings reportedly improved similarly with the two drugs, and the authors described additional anti-fatigue and activating effects with Selank. The abstract gives no numerical between-group estimate or interval. Its description of similarity is not a formal demonstration that the treatments have equal effects.

These are different patient groups, comparators and outcomes. Their reports cannot establish that one peptide is better than the other for a condition that neither study directly compared.

A shared brain-imaging study measured connectivity

Panikratova and colleagues (2020) randomly assigned 52 healthy participants to intranasal Semax (14), Selank (16) or placebo (22). The placebo contained 0.1% nipagin. Resting-state functional MRI was performed before administration and again 5 and 20 minutes afterward. It measured how closely activity in the right amygdala and parts of the right temporal cortex fluctuated together, called functional connectivity.

From 5 to 20 minutes, coordinated activity increased more in each peptide group than in the placebo group in an additional statistical analysis (post hoc; adjusted P<0.05). From baseline to 5 minutes, Semax showed a decrease relative to placebo; Selank did not show an established change against placebo. The study did not establish a between-group difference in connectivity involving the dorsolateral prefrontal cortex, a frontal brain region. The authors described a larger later increase with Semax, but it was tested at a different dose: 1.2 mg versus 0.2 mg Selank. The peptide groups also differed before administration, and the samples were small. These scan results do not establish comparative improvement in anxiety, memory or stroke recovery.

Biological experiments measure particular responses

Dolotov and colleagues (2006) administered Semax to rats and examined the hippocampus, a region involved in memory. BDNF, a protein supporting nerve-cell function, increased up to 1.4-fold, and activation of its TrkB receptor increased up to 1.6-fold. Selected messenger-RNA measurements also increased, and treated rats made more conditioned avoidance responses. These observations connect a rat learning task with a specific biological response without defining a human cognitive benefit.

Selank’s proposed relationship with GABA, the major inhibitory neurotransmitter, comes from separate binding and expression experiments. In Filatova and colleagues’ 2017 study of IMR-32 human tumor-derived cells, Selank alone did not produce an established change in the measured gene transcripts. Adding it with GABA or olanzapine changed their response patterns. A negative single-agent result in this cell system and a combination response answer different questions; neither establishes a clinical interaction or treatment recommendation.

Pharmacokinetics

Zolotarev and colleagues (2006) used tritium, a radioactive hydrogen label, to follow peptide breakdown in experimental plasma, brain tissue and nerve-cell preparations. They identified Selank fragments including TKPRP, TKP, RP and GP. In nerve-cell preparations, Semax mainly yielded HFPGP and PGP. The analytical method separated fragments from the original peptide, an important distinction when interpreting where a label was detected.

The public abstract does not supply a usable human blood concentration-time curve or an established human brain half-life for either compound. Detecting radiolabel or fragments in animal tissue cannot substitute for measuring intact peptide exposure in people. The imaging abstract’s short scan timing also does not establish a duration of clinical benefit.

What safety and regulatory records establish

FDA’s current compounding-safety page names Semax and Selank acetate in its section on nominations that were withdrawn. It raises potential immune reactions associated with peptide aggregation and impurities, and describes important gaps in human safety information for the proposed uses or routes. The Selank entry names an acetate form; its wording is not a safety characterization of every possible derivative.

The July 2026 FDA Semax briefing separately evaluates free base and acetate substances. It finds insufficient evidence for effectiveness in the proposed cerebral-ischemia, migraine and trigeminal-neuralgia uses. Its opening note says the briefing is background for an advisory process rather than the agency’s final determination. Neither that document nor the small clinical reports establishes a relative safety ranking between Semax and Selank.

Frequently asked questions

Does a brain scan prove better memory or less anxiety?

The shared 52-person study measured coordinated fluctuations of brain activity over minutes. Both peptide groups showed a larger increase from 5 to 20 minutes than placebo in a post hoc analysis. Different doses, small groups and a difference already present before treatment limit interpretation. No clinical memory or anxiety benefit was demonstrated.

Does similar symptom improvement mean two treatments are equivalent?

The Selank-medazepam abstract describes similar anxiety effects but gives no difference estimate or interval. A formal equivalence conclusion needs a study designed to exclude clinically important differences; that evidence is not supplied by the abstract.

Is N-acetyl Semax just an acetate salt?

N-terminal acetylation attaches a chemical group to the peptide itself. An acetate salt describes a counterion form. A laboratory comparison found that acetylation changed Semax’s copper binding and protection against copper toxicity.

What is known about human pharmacokinetics?

The cited tracer report describes experimental breakdown products but gives no verified numerical human elimination half-life for either parent peptide. Detecting label or fragments in animal tissue cannot establish how much intact peptide reaches a human brain or how long it remains there.

Semax — full profile · Selected studies

Selank — full profile · Selected studies

Compare other compounds · Explore the guide previews

References

  1. Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat'ko VN, Zhuravleva EIu, Vanichkin AV. [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 1997;97(6):26–34. PMID: 11517472.

    In acute ischemic stroke, 30 patients given Semax were compared with 80 given conventional treatment. Movement problems and selected other neurological deficits improved faster with Semax added to intensive therapy.

  2. Zozulia AA, Neznamov GG, Siuniakov TS, Kost NV, Gabaeva MV, Sokolov OIu, Serebriakova EV, Siranchieva OA, Andriushenko AV, Telesheva ES, Siuniakov SA, Smulevich AB, Miasoedov NF, Seredenin SB. [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(4):38–48. PMID: 18454096.

    Compares 30 Selank and 32 medazepam recipients using symptom scales and a serum enkephalin-related measurement.

  3. Panikratova YR, Lebedeva IS, Sokolov OY, Rumshiskaya AD, Kupriyanov DA, Kost NV, Myasoedov NF. Functional Connectomic Approach to Studying Selank and Semax Effects. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections. 2020;490(1):9–11. DOI: 10.1134/S001249662001007X.

    A randomized 52-person imaging study found more strongly coordinated activity between right-amygdala and temporal regions from 5 to 20 minutes with both peptides than placebo. Baseline imbalance, different doses and small groups limit interpretation.

  4. Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dubynina EV, Novosadova EV, Andreeva LA, Alfeeva LY, Kamensky AA, Grivennikov IA, Myasoedov NF, Engele J. 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. DOI: 10.1016/j.brainres.2006.07.108.

    Identifies MEHFPGP and links rat hippocampal BDNF/TrkB measurements with a conditioned-avoidance response.

  5. Filatova E, Kasian A, Kolomin T, Rybalkina E, Alieva A, Andreeva L, Limborska S, Myasoedov N, Pavlova G, Slominsky P, Shadrina M. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells. Frontiers in pharmacology. 2017;8:89. DOI: 10.3389/fphar.2017.00089.

    In IMR-32 neuroblastoma cells, investigators detected no change in the measured RNA messages with Selank alone. Adding Selank to GABA or olanzapine changed the responses seen with those substances alone.

  6. Zolotarev IuA, Dadaian AK, Dolotov OV, Kozik VS, Kost NV, Sokolov OIu, Dorokhova EM, Meshavkin VK, Inozemtseva LS, Gabaeva MV, Andreeva LA, Alfeeva LIu, Pavlov TS, Badmaeva KE, Badmaeva SE, Bakaeva ZV, Kopylova GN, Samonina GE, Vas'kovskiĭ BV, Grivennikov IA, Zozulia AA, Miasoedov NF. [Evenly tritium-labeled peptides and their in vivo and in vitro biodegradation]. Bioorganicheskaia Khimiia. 2006;32(2):183–191. Russian article; English translation in Russian Journal of Bioorganic Chemistry 32:166–173, DOI: 10.1134/S1068162006020099.

    Identifies Selank and Semax breakdown products through chromatographic separation of labeled peptides; the abstract supplies no human exposure curve.

  7. Magrì A, Tabbì G, Giuffrida A, Pappalardo G, Satriano C, Naletova I, Nicoletti VG, Attanasio F. Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties. Journal of Inorganic Biochemistry. 2016;164:59–69. DOI: 10.1016/j.jinorgbio.2016.08.013.

    Directly studies Ac-Semax chemistry; the acetylated form lost the parent's protective copper-toxicity response in SH-SY5Y cells.

  8. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. Current agency webpage, accessed 13 October 2026.

    Identifies substance-specific gaps in safety, aggregation, impurities and characterization for compounded peptide products.

  9. U.S. Food and Drug Administration. FDA Briefing Document: Pharmacy Compounding Advisory Committee Meeting, July 23–24, 2026. Semax–Related Bulk Drug Substances (Semax (free base) and Semax acetate).

    The agency’s briefing assesses nominated Semax substances and finds insufficient effectiveness evidence for the specified proposed uses; its introductory note distinguishes the briefing from a final determination.

  10. National Library of Medicine. Tuftsin. MeSH Descriptor D014405. Accessed October 15, 2026.

    Defines the Thr-Lys-Pro-Arg sequence that forms the start of Selank.