Selank

Effects measured: Open-label randomized comparison, 30 patients on Selank vs 32 on medazepam. Anxiolytic effect of Selank was reported as similar to medazepam on Hamilton, Zung and CGI scales, and Selank additionally showed antiasthenic and psychostimulant effects that medazepam did not. Patients had reduced serum leu-enkephalin half-life (tau 1/2) at baseline correlating with symptom severity; this normalized/increased during Selank treatment, especially in the GAD subgroup.

Side effects: No specific adverse events are reported in the verified abstract; the authors emphasize Selank lacked the sedative profile of the benzodiazepine comparator.

Sources: Zozulia AA, Neznamov GG, Siuniakov TS, et al. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(4):38-48.

Effects measured: Elevated plus maze, time in open arms. Under chronic stress, Selank alone gave 15.5 s in open arms and diazepam alone 26.9 s, while the Selank + diazepam combination reached 40.8 s (near the pre-stress baseline of ~72.6 s), i.e. the combination was the most effective at restoring open-arm exploration under stress. Without stress, a course of the test drugs actually worsened anxiety indices, but the worsening was least with Selank.

Side effects: No adverse events reported in this study.

Sources: Kasian A, Kolomin T, Andreeva L, Bondarenko E, Myasoedov N, Slominsky P, Shadrina M. Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats. Behav Neurol. 2017;2017:5091027.

Effects measured: Elevated plus maze. In anxiety-prone BALB/c mice, Selank improved exploratory activity and reduced anxiety by both routes, with anxiolytic effect stronger after intraperitoneal injection and nootropic effect stronger after intranasal dosing. Receptor binding differed by route (intraperitoneal raised cortical GABA-site binding ~38 percent; intranasal raised hippocampal NMDA-site binding). In C57BL/6 mice Selank had essentially no behavioral effect by either route, showing strong strain dependence.

Side effects: No adverse events reported in this study.

Sources: Vasil'eva EV, Kondrakhin EA, Salimov RM, Kovalev GI. Comparison of pharmacological effects of heptapeptide selank after intranasal and intraperitoneal administration to BALB/c and C57BL/6 mice. Eksp Klin Farmakol. 2016.

Effects measured: Selank altered [3H]GABA binding to brain membranes acting as a positive allosteric modulator of the GABA receptor system, and could block the modulatory activity of diazepam and olanzapine, indicating overlapping but distinct binding sites. This is the main proposed molecular basis for its benzodiazepine-like anxiolytic effect without classic benzodiazepine binding.

Side effects: Not applicable (in vitro receptor-binding study).

Sources: Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity. Protein Pept Lett. 2018;25(10):914-923.

Effects measured: In vitro at 10^-7 M, Selank fully suppressed IL-6 gene expression in peripheral blood cells of depressed patients (not healthy controls), while raising IL-6 protein concentration in those patient cultures. In vivo, 14 days of Selank shifted the serum Th1/Th2 cytokine balance in GAD/neurasthenia patients, with the changes showing a significant inverse correlation. Authors propose Selank as a candidate immunomodulator in anxiety-asthenic disorders.

Side effects: No adverse events reported in this study.

Sources: Uchakina ON, Uchakin PN, Miasoedov NF, et al. Immunomodulatory effects of selank in patients with anxiety-asthenic disorders. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(5):71-75.