Selank

Selank is a synthetic heptapeptide, Thr-Lys-Pro-Arg-Pro-Gly-Pro (PubChem CID 11765600). Its first four residues are the tetrapeptide tuftsin, followed by Pro-Gly-Pro (Semenova et al., 2008); tuftsin itself was first reported as a natural phagocytosis-stimulating peptide (Najjar and Nishioka, 1970). Published work on the Selank peptide covers enzyme assays in human plasma, rodent behavior, brain and spleen gene expression, brain-slice electrophysiology and a small number of human studies.

It is not that medicine, it is not intended for any clinical use, and it is not for use in people.

Published work on Selank falls into six areas. Each summary below states the model used. Human studies used a Selank drug preparation, not the research material sold here.

Enkephalin-degrading enzymes and opioid signaling

In human plasma in vitro, Selank inhibited enzymatic hydrolysis of enkephalin with a half-maximal inhibitory concentration of about 15 µM, more potently than the peptidase inhibitors bacitracin and puromycin; the same report described shorter enkephalin half-life in the blood of patients with generalized anxiety disorder (Zozulya et al., 2001).

In human serum, Selank and Semax both inhibited enkephalin-degrading enzymes, and their pentapeptide fragments kept that activity while tri-, tetra- and hexapeptide fragments did not (Kost et al., 2001). In mice, Selank lengthened the plasma half-life of leu-enkephalin and changed open-field behavior in the BALB/c strain but not in C57Bl/6 mice (Sokolov et al., 2002).

GABAergic gene expression and synaptic activity

In rat frontal cortex, Selank or GABA changed the expression of 45 of 84 neurotransmission genes at 1 hour and 22 at 3 hours, with a positive correlation between the two treatments at 1 hour, which the authors read as consistent with allosteric modulation of the GABAergic system (Volkova et al., 2016).

In human IMR-32 neuroblastoma cells, Selank alone did not change mRNA levels of these genes, but with GABA it almost completely suppressed the changes GABA produced, and with olanzapine more genes changed than with olanzapine alone (Filatova et al., 2017). In rat hippocampal slices, Selank increased the amplitude and frequency of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons, with no significant concentration dependence between 1 and 8 µM (Povarov et al., 2017).

Immune and inflammation gene expression

In mouse spleen, a single systemic administration of Selank changed the expression of 34 of 84 inflammation-related genes at 6 and 24 hours, including the immune regulator Bcl6 and its target genes (Kolomin et al., 2011). A time-course study found a 3-fold fall in complement C3 mRNA 30 minutes after Selank and similar changes after its Gly-Pro fragment, suggesting that the dipeptide contributes to the parent peptide's activity (Kolomin et al., 2014).

Rodent behavioral models

In outbred rats under naloxone-precipitated morphine withdrawal, Selank lowered the total withdrawal index by 39.6 percent, attenuated convulsive reactions, ptosis and posture disorders and raised the tactile sensitivity threshold 9-fold, performing slightly below diazepam in the same model (Konstantinopolsky et al., 2022). In rats under unpredictable chronic mild stress, anxiety-related measures in the elevated plus maze after combined Selank and diazepam did not differ from pre-stress values (Kasian et al., 2017).

Stability, metabolism and analytical identification

Studies with uniformly tritium-labeled peptide found that Selank is broken down in blood plasma mainly to Thr-Lys-Pro-Arg-Pro, Thr-Lys-Pro, Arg-Pro and Gly-Pro (Zolotarev et al., 2006). Its Pro-Gly-Pro tail places it among the glyproline peptides, which a review described as about as stable as major pharmacological preparations (Ashmarin et al., 2005). For identity testing, a medicines control laboratory that found Selank and Semax in seized preparations developed and validated a liquid chromatography tandem mass spectrometry screen covering ten such peptides (Vanhee et al., 2020).

Human studies

A randomized comparison in 62 patients with generalized anxiety disorder or neurasthenia assigned 30 to Selank and 32 to medazepam; the authors reported similar changes on anxiety rating scales in both groups and a rise in serum leu-enkephalin half-life in the Selank group, mostly in generalized anxiety disorder (Zozulia et al., 2008). In 52 healthy participants, resting-state functional MRI before and after Selank, Semax or placebo found group differences in connectivity between the right amygdala and right temporal cortex (Panikratova et al., 2020).