Cognitive & Neurogenic Peptides (Semax, Selank, Dihexa) — References

Mirrored Reference Dossier

Parent Topic: Cognitive & Neurogenic Peptides (Semax, Selank, Dihexa) | References Hub: 02 - Compounds & Molecules References MOC

---

Landmark Peer-Reviewed Studies

1. Dolotov et al. (2006) — Brain Research

• Citation: Dolotov, O. V., Karpenko, E. A., Inozemtseva, L. S., Seredenina, T. S., Levitskaya, N. G., Rozyczka, J., Dubynina, E. V., Novosadova, E. V., Andreeva, L. A., Alfeeva, L. Y., Kamensky, A. A., Grivennikov, I. A., Myasoedov, N. F., & Engele, J. (2006). Semax, an analogue of ACTH(4–10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research, 1117(1), 54–60.
• Identifiers: PMID: 16996037 (PubMed · Europe PMC) | DOI: 10.1016/j.brainres.2006.07.108 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Quantitative RT-PCR, ELISA protein assay, and conditioned passive avoidance behavioral study in male Wistar rats following intranasal administration of Semax ($50\mu \text{g/kg}$).
• Key Quantitative Outcomes: A single intranasal application of Semax increased hippocampal BDNF protein levels by $+1.4\text{-fold}$ ($+40\%,p<0.05$) at 3 and 24 hours, upregulated exon III BDNF mRNA by $+3\text{-fold}$ ($+200\%,p<0.01$), and increased TrkB receptor tyrosine kinase mRNA by $+2\text{-fold}$ ($p<0.01$), directly enhancing conditioned learning retention.

2. Volkova et al. (2016) — Frontiers in Pharmacology

• Citation: Volkova, A., Shadrina, M., Kolomin, T., Andreeva, L., Limborska, S., Myasoedov, N., & Slominsky, P. (2016). Selank administration affects the expression of some genes involved in GABAergic neurotransmission. Frontiers in Pharmacology, 7, 31.
• Identifiers: PMID: 26924987 (PubMed · Europe PMC) | PMCID: PMC4757669 (PMC Full Text) | DOI: 10.3389/fphar.2016.00031 (DOI · SciDB · Scholar)
• Study Design & Sample Size: PCR-array transcriptomic profiling of 84 neurotransmission-related genes in the frontal cortex of Wistar rats at $1\text{ hour}$ and $3\text{ hours}$ following intranasal Selank ($300\mu \text{g/kg}$) vs. GABA ($300\mu \text{g/kg}$).
• Key Quantitative Outcomes: Out of 84 GABAergic and neurotransmission genes analyzed, Selank produced statistically significant ($\ge 2\text{-fold},p<0.05$) expression changes in 45 genes within $1\text{–}3\text{ hours}$ (including ${\text{GABA}}_{\text{A}}$ subunits Gabra6, Gabrb1, Gabrg2, Gabrd and GABA transporters Slc6a1, Slc6a11). A strong positive correlation was found between the transcriptomic shifts induced by Selank and direct GABA ($r=0.72,p<0.001$), confirming allosteric/epigenetic GABAergic modulation.

3. McCoy et al. (2013) — Journal of Pharmacology and Experimental Therapeutics

• Citation: McCoy, A. T., Benoist, C. C., Wright, J. W., Kawas, L. H., Bikbaeva, J. M., & Harding, J. W. (2013). Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. Journal of Pharmacology and Experimental Therapeutics, 344(1), 141–154.
• Identifiers: PMID: 23055539 (PubMed · Europe PMC) | PMCID: PMC3533412 (PMC Full Text) | DOI: 10.1124/jpet.112.199497 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Microsomal metabolic stability, blood-brain barrier permeability, dissociated hippocampal dendritic spine confocal microscopy, and Morris water maze cognitive rescue in scopolamine-treated and aged Sprague-Dawley rats ($N=8\text{–}10/\text{group}$).
• Key Quantitative Outcomes: Dihexa exhibited a plasma stability half-life $>5\text{ hours}$ in rat liver microsomes (and multi-day in vivo retention), stimulated a $+2.5\text{- to }3\text{-fold}$ increase in hippocampal dendritic spines at $10^{-12}\text{ M}$ (1 picomolar)—roughly $10^7\times$ more potent than BDNF—increased VGLUT1/synapsin/PSD-95 functional glutamatergic synapses, and completely reversed spatial memory deficits in both scopolamine-treated and aged cognitively impaired rats via oral ($1.25\text{–}2.0\text{ mg/kg}$) and i.p. delivery ($p<0.001$).

4. Kost et al. (2001) — Bioorganicheskaia Khimiia (Russian Journal of Bioorganic Chemistry)

• Citation: Kost, N. V., Sokolov, O. I., Gabaeva, M. V., Grivennikov, I. A., Andreeva, L. A., Miasoedov, N. F., & Zozulya, A. A. (2001). Semax andba Selank inhibit the enkephalin-degrading enzymes of human serum. Bioorganicheskaia Khimiia, 27(3), 180–183.
• Identifiers: PMID: 11443939 (PubMed · Europe PMC) | DOI: 10.1023/a:1011373002885 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Human serum enzymatic kinetics and clinical anxiety correlation study comparing Selank and Semax against classic peptidase inhibitors (puromycin, bacitracin).
• Key Quantitative Outcomes: Demonstrated that Selank (${\text{IC}}_{50}=20\mu \text{M}$) and Semax (${\text{IC}}_{50}=10\mu \text{M}$) are more potent inhibitors of human serum enkephalin-degrading enzymes than puromycin (${\text{IC}}_{50}>10\text{ mM}$), protecting endogenous Leu-enkephalin from proteolysis and restoring reduced plasma Leu-enkephalin half-life in patients with Generalized Anxiety Disorder.