Selank: A Research Guide to the Published Literature

Selank is a synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) derived from the endogenous immunopeptide tuftsin, and a narrative review of tuftsin and its analogues catalogued this structural family and the anti-tumour, anti-inflammatory and antimicrobial activities reported for its derivatives across the published literature [1]. Much of the mechanistic interest in Selank has centred on the GABAergic system. In a radioligand–receptor study using isolated brain cell plasma membranes, Selank altered [3H]GABA binding in a manner consistent with positive allosteric modulation, and its combined action with certain benzodiazepines differed from either substance alone, leading the authors to propose partially overlapping but non-identical binding sites [2]. In an electrophysiological experiment on rat hippocampal slices, application of Selank increased the amplitude and discharge rate of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons, with a transient decrease preceding the increase in some cells and no significant concentration dependence across the range tested [3]. Gene-expression work has produced a mixed mechanistic picture. In cultured IMR-32 neuroblastoma cells, Selank alone did not change the mRNA levels of 84 genes involved in GABAergic neurotransmission, but it suppressed most of the expression changes produced by GABA and broadened the set of genes altered by olanzapine [4]. In rat frontal cortex measured by real-time PCR, administration of Selank or GABA was followed by significant changes in the expression of 45 of 84 neurotransmission-related genes at one hour and 22 genes at three hours, with the two compounds showing correlated one-hour profiles [5]. In mouse spleen, Selank and its Gly-Pro fragment shifted the expression of the inflammation-related genes C3, Casp1, Il2rg and Xcr1 over a short time course after a single intraperitoneal injection, with largely overlapping profiles for the peptide and the dipeptide [6]. Rodent behavioural studies form the largest block of the literature. In an elevated plus maze protocol using unpredictable chronic mild stress in rats, Selank given alone produced the largest reduction in the elevated anxiety indices induced by the course of test substances, while the Selank-plus-diazepam combination was the condition that most reduced anxiety indices under chronic stress [7]. In an active avoidance conditioning model, repeated pre-session administration of Selank increased correct responses and decreased errors in rats with initially low learning ability, with effects appearing after the first administration and increasing over repeated sessions; the time course was compared with that of piracetam [8][9]. In depression-related models, repeated administration of Selank counteracted increased immobility in the forced swimming test and reduced sucrose preference in WAG/Rij rats, while single administration shortened immobility in BALB/c mice, with no substantial effect on control Wistar rat behaviour [10]. Neurotrophin signalling has been examined in rats. Intranasal administration of Selank was reported to regulate BDNF expression in the rat hippocampus in vivo [11]. In outbred rats given 10% ethanol as their only fluid for 30 weeks, intraperitoneal Selank was associated with better object-recognition performance during withdrawal and prevented the ethanol-induced rise in BDNF content in hippocampus and frontal cortex in ex vivo measurements [12]. Related withdrawal models report that a single injection of Selank removed elevated anxiety indices in the elevated plus maze and social interaction tests and prevented mechanical allodynia during 48-hour alcohol withdrawal, without changing ethanol consumption [13], and that in naloxone-precipitated morphine withdrawal it lowered the total withdrawal index by 39.6%, attenuated convulsive reactions, ptosis and posture disorders, and raised the tactile sensitivity threshold, remaining slightly below diazepam on these measures [14]. Stress-physiology endpoints outside the brain have also been measured in rodents. In Wistar rats subjected to chronic foot-shock stress, Selank reduced the intensity of stress-induced hepatocyte hydropic degeneration and restored the nucleus/cytoplasm ratio on morphometric analysis [15]. In a sensory-contact "social" stress model in rats, stress raised serum IL-1β, IL-6 and TGF-β1, and Selank administration lowered IL-1β, IL-6, TNF-α and TGF-β1 toward control values [16]. Antiviral properties of structural fragments of Selank have been reported separately [17]. Human data are limited. A resting-state fMRI study in 52 healthy participants compared Selank, Semax and placebo before and after injection and identified condition- and group-dependent differences in functional connectivity between the right amygdala and right temporal cortical regions [18]. A randomised clinical study in patients with anxiety-spectrum disorders compared phenazepam monotherapy with phenazepam combined with selank and reported an earlier onset of change on HDRS and fewer recorded side effects of the benzodiazepine in the combination arm [19]. A 2026 narrative review placing selank among neuroactive peptides of interest in orthopaedics noted that the mechanistic literature for this class is largely preclinical and that clinical trials are currently lacking [20].