Selank

Selank is a synthetic regulatory peptide derived from the naturally occurring tetrapeptide tuftsin, which itself is a fragment of the heavy chain of immunoglobulin G. By appending a Gly-Pro dipeptide to the C-terminus of tuftsin, researchers at the Institute of Molecular Genetics (Russian Academy of Sciences) created a molecule with significantly enhanced metabolic stability and a broader pharmacological profile encompassing both anxiolytic and nootropic properties. Unlike traditional benzodiazepine-based anxiolytics, Selank does not produce sedation, cognitive impairment, or dependence in preclinical and clinical evaluations. This favorable profile has led to its regulatory approval in Russia for the treatment of generalized anxiety disorder (GAD) and neurasthenia, where it is administered intranasally at 0.15% solution concentrations. Its dual mechanism—modulating both the immune system and central neurotransmitter balance—positions it as a unique compound bridging psychoneuroimmunology. Research interest in Selank extends well beyond anxiolysis. Investigations have demonstrated its capacity to influence gene expression profiles related to GABAergic, serotonergic, and dopaminergic neurotransmission, upregulate brain-derived neurotrophic factor (BDNF), and exert immunomodulatory effects via enkephalin metabolism. These multifaceted actions make Selank a subject of ongoing study in cognitive enhancement, stress resilience, and neuroinflammatory conditions. All information presented here is for educational and research purposes only.

Selank exerts its anxiolytic and nootropic effects through several interconnected neurobiological pathways: **GABAergic Modulation**: Selank has been shown to allosterically modulate GABA-A receptor activity and influence the expression of GABA transporter and receptor subunit genes, enhancing inhibitory neurotransmission without the tolerance and dependence risks associated with direct GABA-A agonists such as benzodiazepines. **Serotonin and Dopamine Regulation**: Preclinical studies demonstrate that Selank modulates the metabolism of serotonin (5-HT) and dopamine in key limbic structures including the hypothalamus and hippocampus. It influences monoamine oxidase activity and serotonin transporter expression, contributing to mood stabilization and anxiolysis. **BDNF Upregulation**: One of Selank's most significant actions is the enhancement of brain-derived neurotrophic factor (BDNF) expression in the hippocampus and cortex. BDNF is critical for synaptic plasticity, long-term potentiation, and neuronal survival, underpinning the peptide's pro-cognitive effects. **Enkephalinase Inhibition**: Selank inhibits enzymes responsible for enkephalin degradation, thereby prolonging the activity of endogenous opioid peptides involved in stress response modulation and emotional regulation without producing classical opioid-like effects. **Immunomodulatory Activity**: As a tuftsin analog, Selank retains and extends the parent molecule's ability to modulate innate and adaptive immune responses, influencing cytokine balance (particularly IL-6 and IFN-α) and potentially linking peripheral immune status to central anxiolytic outcomes.

Clinical and preclinical research has produced a substantial body of evidence supporting Selank's pharmacological profile: **Anxiety and Mood Disorders**: A randomized controlled clinical trial in patients with generalized anxiety disorder demonstrated that intranasal Selank (0.15%) produced significant reductions in Hamilton Anxiety Rating Scale scores comparable to the reference anxiolytic medazepam, without the associated sedation or psychomotor impairment. **Gene Expression Studies**: Microarray analyses of hippocampal tissue in animal models revealed that Selank administration alters the expression of 36 genes related to GABAergic neurotransmission, including upregulation of GABA-A receptor subunit genes and the vesicular GABA transporter, providing a molecular basis for its anxiolytic mechanism. **Cognitive Enhancement**: Preclinical studies using Morris water maze and passive avoidance paradigms have demonstrated that Selank improves spatial learning and memory retention, effects that correlate with increased BDNF mRNA levels in the hippocampus and prefrontal cortex. **Neuroprotective Properties**: Research in models of oxidative stress and neurotoxicity has shown that Selank preserves neuronal viability and reduces markers of apoptosis, effects attributed to BDNF-mediated signaling and antioxidant enzyme induction. **Immunomodulation**: Studies in immunocompromised models demonstrate that Selank restores balanced cytokine profiles and enhances phagocytic activity, consistent with its tuftsin heritage and supporting a role in psychoneuroimmunological interactions.

Research protocols for Selank have utilized the following parameters: **Intranasal Administration**: Clinical studies in Russia have employed a 0.15% solution administered intranasally at doses of approximately 250–300 mcg per nostril, typically three times daily, for a total daily dose of approximately 1500–1800 mcg. **Subcutaneous Administration**: Preclinical research protocols have used subcutaneous doses ranging from 100–500 mcg/kg body weight, administered once or twice daily. **Duration of Use**: Clinical trials have evaluated treatment courses of 10–14 days with reported sustained effects extending beyond the treatment period due to gene expression changes. **Important Considerations**: Selank's short plasma half-life is offset by durable CNS effects mediated through gene expression modulation. These are research reference ranges only; Selank is not approved for human therapeutic use outside of Russia, and optimal dosing for all populations has not been established through comprehensive international clinical trials.

Based on available clinical and preclinical data, Selank demonstrates a favorable safety profile: **Clinical Observations**: In controlled trials, Selank was well tolerated with no significant adverse events reported at standard intranasal doses. Notably absent were sedation, muscle relaxation, and the amnestic effects typical of benzodiazepines. **Reported Effects**: - Mild nasal irritation with intranasal administration (transient) - No evidence of tolerance, physical dependence, or withdrawal symptoms - No significant effects on psychomotor performance or reaction time **Theoretical Considerations**: - As an immunomodulatory peptide, effects in individuals with autoimmune conditions remain insufficiently characterized - Long-term safety data beyond 14-day treatment courses is limited - Drug interaction profiles have not been comprehensively evaluated **Research Limitations**: While the safety data from Russian clinical trials and extensive preclinical research is reassuring, large-scale Phase III trials meeting international regulatory standards have not been completed.