Predominance of Nootropic or Anxiolytic Effects of Selank, Semax, and Noopept Peptides Depending on the Route of Administration to BALB/c and C57BL/6 Mice
Vasileva EV, Kondrakhin EA, Abdullina AA, Salimov RM, Kovalev GI
Neurochemical Journal (2020)
The Zakusov Institute's mouse-strain replication of the Manchenko 2010 route-dissociation finding, extended to three peptides (Selank, Semax, Noopept) across two routes (i.p. vs i.n.) and two genetic backgrounds (BALB/c, C57BL/6). In BALB/c — but not in C57BL/6 — anxiolytic efficacy is higher after intraperitoneal injection while nootropic efficacy is higher after intranasal administration.
This is the mouse-strain replication of the Manchenko 2010 route-dissociation paper, conducted at the V.V. Zakusov State Institute of Pharmacology — the same Russian neuropharmacology institute that produced the Zozulya 2008 Selank GAD trial and is institutionally distinct from the Ashmarin / Manchenko / Glazova / Levitskaya group at the Institute of Molecular Genetics and the Moscow State University Faculty of Biology that synthesized Semax and Selank.
Vasileva, Kondrakhin, Abdullina, Salimov, and Kovalev compared three peptides (Selank, Semax, and Noopept) across two routes of administration (intraperitoneal and intranasal) in two inbred mouse strains (BALB/c and C57BL/6), with two output domains: anxiolytic and nootropic / exploratory effects measured in the elevated-plus-maze test, and downstream receptor effects measured as the density of NMDA-receptor binding sites and metabotropic-glutamate-group-II (mGluII) receptor binding sites in cortical brain tissue.
The headline result reproduces the Manchenko 2010 route-dissociation finding in mice with a refinement: the dissociation is strain-dependent. In BALB/c mice — a high-anxiety background — all three peptides via both routes reduced anxiety and improved exploration, but with the route asymmetry the Manchenko program first reported: anxiolytic effect was stronger after intraperitoneal injection, nootropic / exploratory effect was stronger after intranasal administration. In C57BL/6 mice — a low-anxiety background — the same peptides via both routes did not reliably change exploratory behavior or anxiety, with the exception of intraperitoneal Semax, which produced an anxiogenic effect that was absent (or weaker) after intranasal administration.
This is the closest available external replication of the Manchenko route-dissociation result for Semax in the literature. It also extends the route-asymmetry pattern to Selank for the first time in a peer-reviewed Russian/English publication, and it surfaces a strain-by-route interaction (BALB/c vulnerable; C57BL/6 resistant) that the original Manchenko 2010 rat-model paper could not characterize. The receptor-binding readouts (NMDA, mGluII) provide a candidate molecular substrate for the strain-dependence — in C57BL/6 mice, i.p. Semax and i.n. Noopept reduced NMDA-receptor density, and i.p. Noopept and Semax (either route) reduced mGluII-receptor density in cortex, with no parallel behavioral signal.
The full body text of Neurochemical Journal 14(3):268-278 was not directly accessible to the agent-pipeline extraction pass; the structured extraction below is reconstructed from the Springer English-translation abstract, the secondary-source verbatim quotations of that abstract, the program's adjacent papers using the same paradigm (Vasileva 2018 PMID 29787664 on Selank only; Vasileva 2021 Russ J Biol Chem on subchronic Noopept and Semax cortical GABAA-receptor density; Vasileva 2023 on glycine-site NMDA-receptor effects), and the citation of this paper in the companion Manchenko 2010 entry. Specific per-strain × per-route × per-peptide elevated-plus-maze entry counts, percent-open-arm time, and receptor-binding Bmax / Kd values are present in the paper's tables but were not retrievable in this pass.
Structural caveats that apply to the underlying study:
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Strain × dose mismatch. The three peptides were administered at fixed doses each — Selank 300 µg/kg/day, Semax 0.6 mg/kg/day (600 µg/kg/day), Noopept 1 mg/kg/day. The Manchenko 2010 program documented inverted-U dose-response curves for Semax in rats; whether the chosen mouse doses sit at the peak of those curves for either strain is not directly addressed. A null result in C57BL/6 could reflect a strain-specific shift of the dose-response envelope rather than a strain-specific absence of effect.
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Single-paradigm anxiety readout. The elevated-plus-maze is one of several rodent anxiety paradigms; cross-paradigm replication (open field, light-dark box) is not present in this paper. The strain-dependence pattern reported here is paradigm-dependent in principle, even if it tracks broader BALB/c-vs-C57BL/6 anxiety-background differences from the literature.
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Receptor-binding endpoint specificity. The receptor-density readouts are total binding-site density in cortical homogenate, not synaptic density or functional coupling. A change in NMDA or mGluII binding-site density may not translate directly into a change in glutamatergic neurotransmission strength.
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Inventor-institute lineage. The Zakusov Institute is institutionally distinct from the Ashmarin/Manchenko group at Moscow State University that synthesized Semax and Selank, but both are within the Russian peptide neuropharmacology ecosystem and share program-level priors. The Vasileva / Kondrakhin / Kovalev group has continued publishing on these peptides in 2021, 2023, and 2024 with related receptor-binding paradigms — the body of work is internally consistent but not yet independently replicated in a Western laboratory.
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Sex of animals not extracted from abstract. Adjacent papers from the same group use male mice; sex of animals in this specific study was not directly retrievable.
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