Selank vs Semax: Tuftsin Analog vs ACTH(4-10) Analog

Selank and Semax are often sold as a matched nootropic pair. They are not two doses of one molecule.

Semax is a heptapeptide analog of ACTH(4-10): Met-Glu-His-Phe-Pro-Gly-Pro. Selank is a heptapeptide analog of tuftsin: Thr-Lys-Pro-Arg-Pro-Gly-Pro. The research programs overlap in Russian institutes and in the Pro-Gly-Pro tail. The parent peptides, the lead assays, and the clinical questions do not.

Neither peptide has an FDA-approved US product in the sources below. This page is informational, research-use only, and not medical advice.

Research notice: These compounds are discussed for laboratory and literature comparison only. They are not approved for human consumption, medical treatment, or diagnosis in the United States based on the sources cited here.

At a glance

Receptor targets and published mechanisms

These are not clean single-receptor agonists like a GHSR ligand. The papers describe biochemical and expression effects.

Semax. Dolotov et al. (J Neurochem, 2006) found specific, reversible, calcium-dependent binding of tritiated Semax in rat basal-forebrain membranes (Kd 2.4 ± 1.0 nM; Bmax 33.5 ± 7.9 fmol/mg protein). Intranasal Semax in rats raised BDNF protein at 3 hours in basal forebrain, not cerebellum. Dolotov et al. (Brain Res, 2006) reported that a single application in rats produced a maximal 1.4-fold increase in hippocampal BDNF protein, a 1.6-fold increase in trkB tyrosine phosphorylation, and 3-fold / 2-fold increases in exon III BDNF and trkB mRNA, with more conditioned-avoidance reactions. The authors proposed that cognitive effects involve the hippocampal BDNF/trkB system. Those are rodent findings.

Selank. Zozulya et al. (Bull Exp Biol Med, 2001) reported shortened plasma enkephalin half-life in patients with generalized anxiety (not in panic disorder or agoraphobia) and that Selank dose-dependently inhibited enzymatic hydrolysis of plasma enkephalin (IC50 15 micromolar), more potently than bacitracin or puromycin in that comparison. Filatova et al. (2017) reported that Selank, GABA, and olanzapine affected expression of genes involved in GABAergic neurotransmission in IMR-32 cells. Doyno and White (2021) reviewed several GABA-related agents and included Selank in that review; the primary experimental gene-expression paper is Filatova.

Do not upgrade those findings to "Selank is a benzodiazepine" or "Semax is a BDNF drug in humans." The human BDNF claim is not in the Dolotov papers.

Development and regulatory status

Published clinical work cited here appears in Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova and related Russian venues. That documents a clinical research program. It is not an FDA approval, and it is not a reason to treat research vials as licensed medicines.

No US FDA approval for Selank or Semax is included among the sources below. If a jurisdiction has a local registration, it is not verified here and is not used as a claim.

What published research has studied

Semax

• Rodent BDNF/trkB and binding: Dolotov 2006 J Neurochem and Dolotov 2006 Brain Res, summarized above.
• Ischemic stroke (clinical, Russian journal): Gusev, Martynov, Kostenko et al. (2018) reported on Semax in patients at different stages of ischemic stroke (PubMed title contains the journal's spelling "tretament").
• Cerebrovascular insufficiency (clinical, Russian journal): Gusev, Skvortsova, Chukanova (2005) reported on Semax in prevention of disease progress and exacerbations in cerebrovascular insufficiency.
• Acute ischemic-stroke mechanisms: Miasoedova, Skvortsova, Nasonov et al. (1999) investigated neuroprotective-effect mechanisms of Semax in the acute period of ischemic stroke.

Those clinical papers exist and were indexed by PubMed. This page does not extract numeric efficacy claims from them beyond what the indexed titles/abstracts support in English, and it does not convert them into a treatment recommendation.

Selank

• Enkephalinase inhibition: Zozulya et al., 2001, as above.
• GAD and neurasthenia versus medazepam: Zozulia, Neznamov, Siuniakov et al. (2008). Sixty-two patients (30 Selank, 32 medazepam). Anxiolytic effects were described as similar; Selank was also described as having antiasthenic and psychostimulant effects. Patients had decreased leu-enkephalin tau(1/2), which correlated with disease duration and symptom severity; Selank treatment increased that parameter, especially in GAD.
• Anxiety disorders versus phenazepam: Medvedev, Tereshchenko, Israelian et al. (2014). Sixty patients with phobic-anxiety and somatoform disorders (ICD-10 F40.2-9, F41.1-9, F45.0-1). The paper reported a pronounced anxiolytic and mild nootropic effect, with anxiolytic effect described as lasting a week after the last peptide administration, and a positive impact on quality of life.

Those are published clinical comparisons in a Russian journal. They are not FDA trials, and they are not a reason to issue use instructions.

Key differences

If the literature question is anxiety-related enkephalin metabolism, Selank is the peptide with that biochemical and GAD-oriented clinical trail. If the question is ACTH-fragment nootropic work and BDNF in rat hippocampus, Semax is the peptide with those papers. There is no verified head-to-head trial of the two in the sources below.

Peptide pages, vendors, and calculator

• Selank peptide page
• Semax peptide page
• Vendors listing Selank: /stores?peptides=selank
• Vendors listing Semax: /stores?peptides=semax
• Reconstitution math (no dose advice): /tools/peptide-calculator?peptide=selank or Semax

Related: Nootropic and cognitive peptides guide.

References

1. Zozulya AA, Kost NV, Sokolov OY, et al. The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Bull Exp Biol Med. 2001;131(4):315-317. PMID: 11550013. DOI: 10.1023/a:1017979514274.
2. Dolotov OV, Karpenko EA, Seredenina TS, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem. 2006;97 Suppl 1:82-86. PMID: 16635254. DOI: 10.1111/j.1471-4159.2006.03658.x.
3. 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 Res. 2006;1117(1):54-60. PMID: 16996037. DOI: 10.1016/j.brainres.2006.07.108.
4. Gusev EI, Skvortsova VI, Chukanova EI. [Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency]. Zh Nevrol Psikhiatr Im S S Korsakova. 2005. PMID: 15792140.
5. Zozulia AA, Neznamov GG, Siuniakov TS, et al. [Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008. PMID: 18454096.
6. Medvedev VE, Tereshchenko ON, Israelian AIu, et al. [A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2014. PMID: 25176261.
7. Filatova E, Kasian A, Kolomin T, et al. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells. Front Pharmacol. 2017;8:89. PMID: 28293190. DOI: 10.3389/fphar.2017.00089.
8. Gusev EI, Martynov MY, Kostenko EV, et al. [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018. PMID: 29798983. DOI: 10.17116/jnevro20181183261-68.
9. Miasoedova NF, Skvortsova VI, Nasonov EL, et al. [Investigation of mechanisms of neuro-protective effect of semax in acute period of ischemic stroke]. Zh Nevrol Psikhiatr Im S S Korsakova. 1999. PMID: 10358912.
10. Doyno CR, White CM. Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank. J Clin Pharmacol. 2021;61(Suppl 2):S114-S128. PMID: 34396551. DOI: 10.1002/jcph.1922.