Selank

Overview

Selank (TP-7) is a synthetic heptapeptide developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is a structural analog of the endogenous immunomodulatory peptide tuftsin (Thr-Lys-Pro-Arg), with an appended Pro-Gly-Pro tripeptide tail that confers resistance to enzymatic degradation and extends its biological half-life.

Approved in Russia since 2009 as an intranasal anxiolytic and nootropic medication, Selank represents a unique pharmacological class: it provides clinically meaningful anxiolysis through GABAergic modulation without the sedation, cognitive impairment, tolerance, or physical dependence associated with benzodiazepines. Its dual anxiolytic-nootropic profile, combined with immunomodulatory properties inherited from the tuftsin core, makes it a peptide of interest for prescribers exploring alternatives to conventional anxiolytics.

Mechanism of Action

Selank exerts its pharmacological effects through four interconnected signaling pathways, reflecting the multifunctionality of its tuftsin-derived structure:

GABAergic Modulation

Selank enhances inhibitory GABAergic neurotransmission by allosterically modulating GABA-A receptors at a binding site distinct from the classical benzodiazepine site. This mechanism increases chloride channel conductance and neuronal hyperpolarization, reducing excitability in anxiety-related circuits (amygdala, prefrontal cortex) without producing the sedative, amnestic, or dependence-inducing effects characteristic of benzodiazepine-site agonists.

Serotonergic and Monoaminergic Pathway

Selank increases serotonin (5-HT) metabolism and turnover in the hippocampus, frontal cortex, and hypothalamus. It modulates expression of serotonin receptor genes, particularly 5-HT1A and 5-HT2A subtypes. Additionally, studies demonstrate effects on dopaminergic and noradrenergic systems, with altered dopamine metabolism in striatal and limbic regions. This broad monoaminergic modulation contributes to both anxiolytic and procognitive effects.

BDNF and Neuroplasticity

Selank robustly upregulates brain-derived neurotrophic factor (BDNF) expression in the hippocampus following intranasal administration. BDNF activates TrkB receptors, triggering CREB phosphorylation and downstream gene transcription programs that promote synaptic plasticity, dendritic arborization, and long-term potentiation (LTP). This neurotrophic pathway underlies the nootropic properties of Selank and its potential for cognitive enhancement and neuroprotection.

Immunomodulation via Tuftsin Core

The tuftsin tetrapeptide core (Thr-Lys-Pro-Arg) retained in Selank activates monocytes and macrophages through Fc-gamma receptors, modulating production of IL-6, IFN-gamma, and the Th1/Th2 cytokine balance. Selank also inhibits enkephalinase (neprilysin), the enzyme responsible for degrading endogenous enkephalins, thereby preserving endogenous opioid peptide tone. This neuro-immune interface represents a distinctive feature linking anxiolytic and immunomodulatory activities.

Clinical Evidence

The clinical evidence base for Selank is predominantly derived from Russian research institutions. While the peptide has demonstrated consistent anxiolytic and nootropic effects across multiple studies, the evidence has important limitations that prescribers should understand:

Anxiolytic Efficacy

Russian Phase II/III clinical trials demonstrated anxiolytic efficacy comparable to medazepam (a benzodiazepine) in patients with generalized anxiety disorder and adjustment disorders. Key findings include significant reductions in Hamilton Anxiety Rating Scale (HAM-A) scores, with onset of effect within the first week of intranasal administration and sustained benefit throughout 14-day treatment courses. Notably, no sedation, cognitive impairment, or dependence was observed.

Nootropic Effects

Preclinical studies demonstrate improved learning and memory in multiple animal models, including conditioned avoidance reflexes and spatial memory tasks. Clinical observations in Russian studies report improvements in attention, working memory, and cognitive flexibility during Selank treatment courses. These effects are attributed to the combined BDNF upregulation and monoaminergic modulation.

Immunomodulatory Effects

Clinical studies in patients with anxiety-asthenic disorders showed normalization of immune parameters including T-lymphocyte subsets and cytokine profiles following Selank treatment. The immunomodulatory effects are consistent with the well-characterized activity of the parent peptide tuftsin and may contribute to the overall therapeutic benefit in patients with stress-related immune dysregulation.

Evidence Limitations

• All clinical trials were conducted in Russia and are not registered on ClinicalTrials.gov
• Most publications are in Russian-language journals with limited English-language indexing
• Sample sizes are generally small (20-60 patients per study)
• No placebo-controlled RCTs meeting ICH-GCP standards have been published
• No FDA, EMA, or MHRA regulatory review has been conducted
• Long-term safety data (beyond 6-month follow-up) are limited

Dosing Protocols

Administration Guidelines

Intranasal Administration

• Clear nasal passages before administration
• Tilt head slightly forward; do not tilt backward
• Insert dropper tip just inside the nostril without touching nasal mucosa
• Administer prescribed number of drops
• Breathe gently through the nose to distribute solution
• Avoid blowing nose for at least 5 minutes after administration
• Alternate starting nostril between doses

Subcutaneous Injection

• Reconstitute lyophilized powder with bacteriostatic water per pharmacy instructions
• Inject subcutaneously in the abdominal area, rotating injection sites
• Store reconstituted solution refrigerated at 2-8°C
• Use reconstituted solution within 14 days

Regulatory Status

Selank occupies a complex regulatory position that varies significantly by jurisdiction:

• Russia: Approved as an anxiolytic/nootropic intranasal spray (0.15% solution) since 2009. Available by prescription.
• United States: NOT FDA-approved. Listed on the FDA safety-risk list for compounding substances. Not scheduled under the Controlled Substances Act. Compounding availability may be restricted.
• European Union: Not evaluated by the EMA. Not approved in any EU member state.
• Other jurisdictions: Not approved by MHRA (UK), TGA (Australia), or Health Canada.

Patient Counseling Points

• Selank is not FDA-approved. Explain the evidence base and its limitations, including reliance on Russian clinical data.
• Anxiolytic effects typically begin within the first week but full benefit develops over 7-14 days of regular use.
• Unlike benzodiazepines, Selank does not cause sedation, cognitive impairment, or physical dependence in published studies.
• Intranasal administration requires proper technique for optimal absorption — provide demonstration.
• Report any unusual nasal symptoms (persistent irritation, bleeding, congestion) during intranasal use.
• Complete the prescribed course duration (typically 14-21 days); do not discontinue prematurely.
• Inform all treating providers that you are using Selank, particularly if taking anxiolytics, antidepressants, or immunosuppressants.
• Store reconstituted/opened solution in the refrigerator and discard after 14 days.