Inside the body with Selank

The Russian label reports absolute bioavailability of 92.8% after intranasal administration, detection in plasma at 30 seconds, rapid distribution to tissues and penetration into brain tissue. These figures come from the manufacturer's registered label; the underlying study was not located, and no independent human pharmacokinetic paper was found. Researchers chose the intranasal route in rat studies because it is considered efficient for delivering peptides to the central nervous system.[src][src]

The Pro-Gly-Pro extension was designed to improve metabolic stability and give a longer duration of action than tuftsin. The Russian label states that plasma concentration declines progressively over about 5 to 5.5 minutes and that neither unchanged drug nor metabolites are found in 24-hour urine, attributed to rapid degradation by tissue peptidases. This is a label statement, not a formally reported half-life. The fragment Gly-Pro has been reported to reproduce some Selank effects on gene expression in mouse spleen, so fragments may contribute to activity (animal data).[src][src][src]

In radioligand binding on rat brain plasma membranes, Selank acted as a positive allosteric modulator of [3H]GABA binding, with a combined effect with some benzodiazepines that was not simply additive, and it could block the modulatory activity of diazepam and olanzapine in that assay (Vyunova et al., 2018). Intranasal Selank in male Wistar rats changed expression of 29 of 77 analysed neurotransmission genes in frontal cortex at 1 h and 17 at 3 h (45 and 22 when Selank and GABA results are pooled), and changes at 1 h correlated positively with those after GABA itself (Volkova et al., 2016). In human IMR-32 neuroblastoma cells Selank alone did not change GABAergic gene mRNA levels but altered the effect of GABA and olanzapine on them (2017). All of this is animal or in vitro; direct GABA-A receptor modulation in humans has not been demonstrated.[src][src][src]

In blood plasma in vitro, Selank inhibited enkephalin hydrolysis in a concentration-dependent way (IC50 15 microM) and was more potent than bacitracin and puromycin; patients with generalized anxiety disorder, but not panic disorder or agoraphobia, had a shortened enkephalin half-life and reduced total enkephalinase activity in blood (Zozulya et al., 2001). In the 62-patient GAD/neurasthenia study, leu-enkephalin half-life was reduced at baseline, correlated with anxiety, asthenia and autonomic symptoms, and rose during Selank treatment, mostly in patients with GAD (Zozulia et al., 2008). This is an association in small studies; a causal route to the clinical effect is not proven.[src][src]

In outbred rats drinking 10% ethanol for 30 weeks, intraperitoneal Selank for 7 days prevented ethanol-induced memory and attention disturbances in the object recognition test and prevented the ethanol-induced increase of BDNF content in hippocampus and frontal cortex measured ex vivo (Kolik et al., 2019). Effects on BDNF have not been shown in humans.[src]

In mouse spleen after a single intraperitoneal injection, Selank changed expression of 34 of 84 inflammation-related genes, with Bcl6 altered by Selank and its fragments (Kolomin et al., 2011). In human blood, 14 days of Selank in patients with GAD and neurasthenia was associated with shifts in the Th1/Th2 cytokine balance, and in vitro Selank suppressed IL-6 gene expression in blood cells from patients with depression but not from healthy controls, while the same abstract reports a rise in IL-6 concentration in patients' blood-cell cultures with Selank (Uchakina et al., 2008). These are small studies with no clinical immune endpoints.[src][src]

In 62 patients with GAD and neurasthenia, Selank (n=30) and medazepam (n=32) had similar anxiolytic effects on Hamilton, Zung and CGI scales, and Selank additionally showed antiasthenic and psychostimulant effects (Zozulia et al., 2008). In 60 patients with phobic-anxiety and somatoform disorders, a comparison with phenazepam reported pronounced anxiolytic and mild nootropic effects of Selank, with the anxiolytic effect lasting a week after the last administration; the abstract gives no comparative figures (Medvedev et al., 2014). In 70 patients (40 on Selank plus phenazepam, 30 on phenazepam alone), the combination gave an earlier effect on HDRS and fewer phenazepam side effects than phenazepam alone (Medvedev et al., 2015). Blinding and placebo control are not described in the abstracts, and no replication outside Russia was found. In rats, Selank plus diazepam gave the largest reduction in anxiety under chronic mild stress (Kasian et al., 2017; animal only).[src][src][src][src]