N-Acetyl Selank

N-Acetyl Selank is an enhanced synthetic heptapeptide derived from the endogenous immune peptide tuftsin, featuring acetylation for improved stability and bioavailability. It functions as a potent anxiolytic and nootropic compound with demonstrated effects on GABAergic, dopaminergic, and serotonergic neurotransmission. Originally developed by the Institute of Molecular Genetics of the Russian Academy of Sciences and approved for anxiety disorder treatment in Russia, it exhibits neuroprotective, immunomodulatory, and cognitive-enhancing properties without the side effects typical of benzodiazepines.

Anxiolytic Effects

N-Acetyl Selank demonstrates pronounced anxiolytic activity comparable to benzodiazepine tranquilizers but without characteristic side effects such as amnesia, withdrawal, or dependence ^[1][2][3]. In clinical trials with 62 patients diagnosed with generalized anxiety disorder (GAD) and neurasthenia, Selank showed anxiolytic effects similar to medazepam while also providing antiasthenic and psychostimulant benefits ^[2]. The peptide enhances the effect of diazepam in reducing anxiety, suggesting it not only modulates GABAA receptors allosterically but also increases the affinity of benzodiazepines to these receptors ^[3]. In comparative studies with phenazepam, Selank demonstrated pronounced anxiolytic and mild nootropic effects with benefits persisting for a week after the last dose ^[14].

Cognitive Enhancement

Selank significantly activates learning processes in rats with initially poor learning ability, with improvements visible after the first dose ^[4]. The peptide induces increased memory trace stability for 30 days when administered during memory consolidation phases ^[17]. It protects against ethanol-induced memory impairment by regulating BDNF content in the hippocampus and prefrontal cortex, demonstrating cognitive-stimulating effects and prevention of alcohol-related memory problems ^[5]. Selank restored cognitive processes disordered by chronic inhibition of the cerebral catecholaminergic system at doses of 300 μg/kg ^[12].

Neuroprotection

The peptide demonstrates significant neuroprotective properties across multiple injury models. It recovers learning and memory impaired by neurotoxic damage to the noradrenergic brain system, including damage from 6-OHDA administration and hypoxic conditions ^[11]. In Parkinson's disease models, Selank decreased anxiety levels in rats with toxic damage to dopaminergic neurons while maintaining efficacy even with substantia nigra damage ^[13]. Administration of Selank corrects measures of integrative brain activity and biogenic amine levels in adult rats resulting from antenatal hypoxia, improving sensory attention by 2-3 fold and learning facilitation by 1.5 times ^[16].

BDNF Regulation

Selank regulates brain-derived neurotrophic factor (BDNF) expression in key brain regions. Intranasal administration rapidly elevates BDNF expression in the rat hippocampus in vivo ^[6]. The peptide prevented ethanol-induced increases in BDNF content in the hippocampus and frontal cortex, confirming involvement of neurotrophin mechanisms related to BDNF production ^[5].

Immunomodulation

Selank exhibits potent immunomodulatory effects, completely suppressing IL-6 gene expression in peripheral blood of patients with depression at concentrations of 10⁻⁷ M while modulating Th1/Th2 cytokine ratios ^[7]. Under conditions of social stress, Selank reduces concentrations of IL-1β, IL-6, TNF-α, and TGF-β1 to near-control values ^[10]. The peptide demonstrates antiviral activity against influenza A/Aichi 2/68 (H3N2), completely suppressing viral reproduction in cell cultures and inducing interferon-alpha expression without affecting IL-4, IL-10, or TNF-α ^[8].

Neurotransmitter Modulation

Selank administration affects the expression of 84 genes involved in GABAergic neurotransmission, with 45 genes showing significant expression changes at 1 hour and 22 genes at 3 hours following administration ^[1]. The peptide activates dopamine receptor Drd5 expression, which plays a key role in memory formation and learning processes through long-term potentiation ^[1]. A single injection activates serotonin metabolism in the hypothalamus and caudal brain stem for 30 minutes to 2 hours, with nootropic effects likely resulting from enhanced 5-HT metabolism ^[17]. In human neuroimaging studies, Selank modulates functional connectivity between the right amygdala and temporal cortex regions ^[18].

Antidepressant Properties

In high doses (1000-2000 μg/kg) after repeated injection, Selank counteracted symptoms of depression in WAG/Rij rats, including increased immobilization in forced swimming tests and anhedonia ^[15]. The neurobiochemical spectrum includes activation of brain monoaminergic systems, dopamine synthesis and turnover, and modulation of tyrosine hydroxylase activity ^[15].

Clinical Safety Profile

Selank has demonstrated an excellent safety profile in clinical trials and experimental studies. Unlike benzodiazepine tranquilizers, Selank does not produce characteristic side effects such as amnesia, withdrawal symptoms, or dependence ^[3][14]. The anxiolytic effect of Selank is comparable to low doses of benzodiazepine tranquilizers, but the action of Selank is not accompanied by the unwanted side effects of those drugs ^[3].

Tolerability

In comparative clinical studies with phenazepam involving 60 patients with phobic-anxiety and somatoform disorders, Selank showed good tolerability and positively influenced patient quality of life ^[14]. The peptide demonstrated pronounced anxiolytic and mild nootropic effects with therapeutic benefits persisting for a week after the last dose ^[14].

Regulatory Status

Selank was approved for human use by the Russian Federation Ministry of Health in 2009 for the treatment of generalized anxiety disorder (GAD). It is currently available by prescription only in Russia and Ukraine. The compound has not been approved by the FDA for use in the United States and remains classified as an experimental peptide in most countries.

Dosing and Administration

Most research studies utilized doses ranging from 300 μg/kg to 2000 μg/kg in animal models ^{[4][11][15][16]}. The peptide has been administered via intranasal, intraperitoneal, and subcutaneous routes in various studies. Intranasal administration has been shown to effectively regulate BDNF expression in the hippocampus and modulate brain neurotransmitter systems ^[6].

Cardiovascular and Respiratory Effects

Studies examining cardiovascular and respiratory system functioning found no significant adverse effects from Selank administration, supporting its overall safety profile.

Immunological Safety

Selank demonstrates immunomodulatory rather than immunosuppressive effects, helping to maintain immune system balance by modulating Th1/Th2/Treg cytokine equilibrium both directly and indirectly via the central nervous system ^[7][8]. The antiviral action mechanism appears to involve selective interferon-alpha induction without affecting other inflammatory cytokines ^[8].

Drug Interactions

Selank has been studied in combination with benzodiazepines, where it enhanced the anxiolytic effects of diazepam while potentially allowing for reduced benzodiazepine dosing and associated side effects ^[3]. This suggests potential utility as an adjunct therapy to reduce benzodiazepine requirements.

Long-term Use

Studies have examined repeated administration over periods ranging from 7 to 30 days, with memory trace stability improvements persisting for 30 days after treatment ^[17]. The anxiolytic effects have been shown to last for at least one week after the final dose ^[14]. No tolerance or dependence has been reported in clinical studies.

Contraindications and Precautions

As an experimental compound not approved in most jurisdictions, comprehensive safety data for special populations (pregnancy, lactation, pediatric use) is limited. The peptide has been primarily studied in adult animal models and adult human populations with anxiety disorders. Individuals should consult healthcare providers before use, particularly those with pre-existing medical conditions or taking other medications.