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Selank

Selank

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Synthetic heptapeptide tuftsin analog with Pro-Gly-Pro C-terminal extension; anxiolytic GABA-A positive allosteric modulator with immunomodulatory and nootropic properties, without benzodiazepine-type dependence or sedation.

Quick Facts

Property Value
Also Known As TP-7, Thr-Lys-Pro-Arg-Pro-Gly-Pro, Selanc
Category Cognitive / Anxiolytic
Sequence TKPRPGP (7 amino acids; tuftsin tetrapeptide TKPR + Pro-Gly-Pro)
Molecular Weight ~751 Da
Molecular Formula C33H57N11O9
PubChem CID 11765600
Administration Intranasal (primary), SubQ
Typical Dose Range 250-500 mcg intranasal, 1-3x daily
Half-Life ~30 minutes
Storage Lyophilized: -20C, stable 1-2 years. Reconstituted/solution: 2-8C, use within 2-4 weeks.
FDA Status Not FDA-approved. Approved in Russia for Generalized Anxiety Disorder (GAD).
WADA Status Prohibited under S0 (Non-Approved Substances)

Mechanism of Action

Selank is a synthetic analog of tuftsin (Thr-Lys-Pro-Arg), an endogenous immunomodulatory tetrapeptide derived from the Fc region of IgG, stabilized by the addition of a Pro-Gly-Pro (PGP) C-terminal extension that confers resistance to aminopeptidase degradation and extends its biological activity. This dual origin — tuftsin backbone plus PGP motif (shared with Semax) — gives Selank a unique pharmacological profile that bridges anxiolytic, nootropic, and immunomodulatory actions.

The primary anxiolytic mechanism of Selank operates through positive allosteric modulation of GABA-A receptors. Electrophysiological and gene expression studies demonstrate that Selank modulates GABAergic neurotransmission in a subtype-selective and concentration-dependent manner, potentiating inhibitory signaling without directly binding the benzodiazepine site. Notably, Selank blocks the modulatory activity of diazepam at GABA-A receptors, indicating it engages a distinct allosteric site (PMID-26924987, PMID-28293190). This mechanism accounts for its anxiolytic efficacy comparable to benzodiazepines but without dependence, tolerance, sedation, or withdrawal — a critical clinical differentiator (PMID-30255741).

Selank's immunomodulatory properties derive from its tuftsin origin. In a human clinical study of patients with GAD and concurrent neurasthenia, Selank treatment normalized aberrant cytokine profiles, significantly suppressing IL-6 levels and rebalancing Th1/Th2 immune responses, demonstrating that its anti-anxiety effects are accompanied by measurable immunological normalization (PMID-18577961). Animal studies confirm that Selank modulates cytokine expression under social stress conditions, further linking its anxiolytic and immunomodulatory actions (PMID-32621722).

Additionally, Selank regulates BDNF expression and modulates the opioidergic system, with studies demonstrating that its anxiolytic effects involve enkephalinase inhibition and interaction with endogenous opioid peptide pathways (PMID-22550852, PMID-15508574). Human fMRI data shows Selank alters functional connectivity patterns in brain regions associated with anxiety and cognitive processing, providing direct neuroimaging evidence for its central effects (PMID-32342318).

Key Research Areas

  1. GABA-A Allosteric Modulation — Selank acts as a positive allosteric modulator of GABA-A receptors through a non-benzodiazepine binding site, producing anxiolysis without sedation, dependence, or tolerance. It blocks diazepam modulatory activity, indicating a distinct mechanism (PMID-26924987, PMID-28293190, PMID-30255741).

  2. Human Clinical Immunomodulation — In GAD patients, Selank normalized cytokine profiles (IL-6 suppression, Th1/Th2 rebalancing), linking anxiolytic therapy to immune system normalization (PMID-18577961).

  3. Human Functional Neuroimaging — fMRI studies demonstrate Selank-induced changes in functional connectivity in anxiety- and cognition-related brain networks in healthy volunteers (PMID-32342318).

  4. Ethanol-Induced Memory Protection — Selank protects against ethanol-induced memory impairment in animal models, suggesting a role in neuroprotection during toxic exposure (PMID-31625062).

  5. Stress Cytokine Modulation — Under social stress conditions, Selank modulates pro-inflammatory cytokine expression, providing a biological link between stress resilience and immune regulation (PMID-32621722).

  6. Opioid System Interaction and Anxiolysis — Selank's anxiolytic properties involve the endogenous opioid system, including enkephalinase inhibition and novel interactions with opioid peptide pathways (PMID-22550852, PMID-15508574).

Evidence Level Summary

Evidence Type Count Notes
Human RCTs 0 Russian Phase III GAD trials exist but are published in Russian-language journals
Human observational / clinical 2 Clinical immunomodulation study (PMID-18577961); fMRI functional connectivity (PMID-32342318)
Animal in vivo 4 GABA-A modulation, stress models, ethanol memory protection, morphine withdrawal
In vitro 0 —
Systematic reviews 0 —
Narrative reviews 5 Including molecular mechanism reviews, anxiolytic comparison, opioid system analysis

Note on evidence: Selank is approved in Russia for Generalized Anxiety Disorder based on Phase III clinical trials. However, the pivotal trial data is largely published in Russian-language journals and is not fully accessible in English-language databases. The English-language evidence supports the mechanism and provides human-level data, but the formal clinical efficacy dataset remains underrepresented.

Clinical Applications

  • Anxiety — Primary indication; GABA-A allosteric modulation provides benzodiazepine-comparable anxiolysis without dependence
  • Cognitive Enhancement — BDNF upregulation and functional connectivity modulation support nootropic effects
  • Neuroprotection — Protection against neurotoxic insults (ethanol, stress-induced neuroinflammation)
  • Immune Support — Tuftsin-derived immunomodulation with IL-6 suppression and Th1/Th2 normalization

Protocols Using This Peptide

Ageless Peps Products

  • AP-Selank-Vial — Selank Vial, $37, intranasal/SubQ

Dosing Reference

Research Dosing Ranges (from literature)

Route Dose Range Frequency Duration Source
Intranasal 250-500 mcg 1-3x daily 3 weeks on / 1 week off Russian clinical protocols
Intranasal 100-250 mcg 1-2x daily First week (introductory) Practitioner guides
SubQ 150-300 mcg 1x daily 2-4 weeks Practitioner guides

Cycling

Standard cycling is 3 weeks on / 1 week off. No dependence, tolerance, or withdrawal has been reported in clinical use, and cycling is recommended primarily as a precautionary measure to maintain receptor sensitivity rather than due to observed tolerance.

Contraindications & Safety

  • Contraindications: Concurrent benzodiazepine use (allosteric competition at GABA-A receptors; Selank blocks diazepam modulatory activity, potentially reducing benzodiazepine efficacy). Use caution with other GABAergic agents.
  • Common side effects: Mild nasal irritation with intranasal use; transient fatigue during first 1-2 days of use (self-resolving).
  • Drug interactions: Benzodiazepines (allosteric competition — see PMID-26924987). Theoretical interaction with other GABAergic compounds (barbiturates, gabapentinoids). No formally documented interactions with SSRIs or SNRIs, though co-administration should be monitored.
  • Pregnancy/nursing: Insufficient data; not recommended.
  • Special populations: Russian clinical approval data suggests good tolerability with no abuse potential. No specific data on renal/hepatic impairment or pediatric populations in English literature.

Translation limitation: Russian Phase III clinical trial data supporting GAD approval is largely unavailable in English. Practitioners should note the approved clinical use abroad while recognizing the limitations of the English-language evidence base.

Cancer Considerations

CAUTION — No direct safety data; tuftsin parent peptide is anti-tumor. No published studies evaluate Selank in patients with active tumors. However, the parent peptide tuftsin demonstrates predominantly anti-tumor activity: macrophage-mediated tumoricidal effects (PMID-3627109), competitive VEGF antagonism at neuropilin-1 (PMID-16371354), and enhanced anti-tumor immune responses in multiple cancer models. Selank does NOT promote angiogenesis (unlike BPC-157, TB-500, GHK-Cu). Its GABAergic and anti-inflammatory mechanisms are not directly pro-tumorigenic. However, the complete absence of cancer-specific Selank data means it cannot be declared safe in active malignancy. Avoid during active cancer; may be considered in remission with oncologist approval. See Compliance/Cancer Safety Matrix.

Synergistic Combinations

  • Semax + Selank — Complementary cognitive-anxiolytic "flow state" stack. Selank provides anxiolysis and emotional calm via GABA-A modulation; Semax provides cognitive drive via BDNF/dopamine enhancement. Both share the PGP stabilization motif and intranasal route. Human fMRI confirms distinct but complementary brain connectivity effects (PMID-32342318).
  • BPC-157 + Selank — Neuroprotection stack; BPC-157 provides broad tissue repair and neuroprotective signaling that complements Selank's GABAergic and immunomodulatory actions.
  • P21 + NSI-189 + Selank — Neurogenesis stack combining anxiolysis with hippocampal neurogenesis promotion.

Related Research

PMID Title Year Study Type
PMID-15508574 – A new property of the synthetic anxiolytic Selank and its de A new property of the synthetic anxiolytic Selank and its derivatives 2004 Narrative review
PMID-18577961 – Selank Immunomodulatory Effects in Anxiety Patients Selank Immunomodulatory Effects in Anxiety Patients 2008 Human clinical
PMID-22550852 – [The role of opioid system in peculiarities of anti-anxiety The role of opioid system in peculiarities of anti-anxiety effect of peptide anxiolytic selank 2012 Animal in vivo
PMID-25176261 – [A comparison of the anxiolytic effect and tolerability of s A comparison of the anxiolytic effect and tolerability of selank and phenazepam 2014 Narrative review
PMID-26924987 – Selank Affects GABAergic Neurotransmission Gene Expression Selank Affects GABAergic Neurotransmission Gene Expression 2016 Animal in vivo
PMID-28293190 – GABA, Selank, and Olanzapine Affect the Expression of Genes GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells 2017 Animal in vivo
PMID-30255741 – Peptide-based Anxiolytics Selank Molecular Mechanisms Peptide-based Anxiolytics: Selank Molecular Mechanisms 2018 Narrative review
PMID-31625062 – Selank Protects Against Ethanol-Induced Memory Impairment Selank Protects Against Ethanol-Induced Memory Impairment 2019 Animal in vivo
PMID-32342318 – Functional Connectomic Approach to Semax and Selank Effects Functional Connectomic Approach to Semax and Selank Effects 2020 Human neuroimaging
PMID-32621722 – Selank Cytokines Under Social Stress Selank Cytokines Under Social Stress 2020 Narrative review
PMID-36322304 – Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Sig Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats 2022 Animal in vivo

References

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#peptide #cognitive #intranasal #subq