Selank: Mechanism of Action
Mecanismo de Acao
Dual Mechanism: GABA-A Modulation + Enkephalinase Inhibition
Selank possesses um(a) unico(a) dual mecanismo de acao distinguishing it from classical anxiolytics:
1. GABA-A Receptor Positive Allosteric Modulation
Selank acts como um(a) positivo(a) allosteric modulator (PAM) do(a) GABA-A receptor. Its binding site is distinto(a) de the classical benzodiazepine site, though partial overlap may exist.[8] This modulacao aprimora the affinity of o receptor for GABA, increasing inhibitory neurotransmission sem producing sedation, amnesia, or muscle relaxation.[5]
Selank administration significantly alters mRNA levels of GABA receptor subunits — Gabrb3, Gabre (epsilon), and Gabrq (theta) — assim como the GABA transporter Slc6a13 (GAT-2) no(a) frontal cortex. Dramatically, Gabre and Gabrq diminuiu aproximadamente 20-fold at 1 hour, enquanto Hcrt (orexin/hypocretin) diminuiu 25-fold then surged 128-fold by 3 hours.[9] This orexin rebound is hypothesized to explana ausencia de sedation typical of benzodiazepines.
2. Enkephalinase Inhibition
Selank competitively inibe enzymes responsavel por the degradacao of enkephalins (endogenous opioid peptides), incluindo aminopeptidases, carboxypeptidase H, and angiotensin-converting enzyme (ACE). The inhibitory effect has an IC50 of aproximadamente 15–20 μM in human serum assays.[10] This extends the meia-vida of Leu-enkephalin, potentiating the body's natural stress-limiting and analgesic pathways.[11]
BDNF/TrkB Signaling
Selank rapidly elevates expression of Brain-Derived Neurotrophic Factor (BDNF) e seu(sua) receptor TrkB. An increase in Bdnf mRNA is observado(a) no(a) hippocampus as precoce as 90 minutes, with protein levels increasing by 24 hours.[12]
Monoamine Neurotransmitter Modulation
Selank induz region-specific changes in monoamine metabolismo:
- Serotonin: Increased 5-HIAA (metabolite) in hypothalamus and brainstem within 30 minutes to 2 hours[13]
- Norepinephrine: Increased no(a) hypothalamus[13]
- Dopamine: Strain-dependent — diminuiu metabolites in high-anxiety (BALB/c) mice, aumentou in low-anxiety (C57BL/6) mice[13]
Immunomodulacao
Selank modula IL-6 expression, normalizes the Th1/Th2 cytokine balance, and induz interferon-alpha (IFN-α) secretion.[14]
Receptor Selectivity
Importante, radioreceptor assays show que Selank does not directly displace ligands from benzodiazepine, dopamine (D2), serotonin (5-HT2), or opioid (μ, δ) receptors. Its effects on these systems are downstream or allosteric.[8] No entanto, the opioid antagonist naloxone bloqueia Selank's anxiolytic effects, confirming the enkephalin system's involvement.[15]
“Estes produtos não são medicamentos ou fármacos e não foram aprovados pelo FDA dos EUA para prevenir, tratar ou curar qualquer condição médica, enfermidade ou doença.”
Referencias
- Kolomin TA, Shadrina M, Slominsky P, Limborska SA, Myasoedov NF. A New Generation of Drugs: Synthetic Peptides Based on Natural Regulatory Peptides. Neuroscience & Medicine. 2013;4(4):223–252.
- Vyunova TV, Andreeva LA, Shevchenko KV, Myasoedov NF. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity. Protein & Peptide Letters. 2018;25(10):914–923.
- Medvedev VE, Tereshchenko ON, Kost NV, et al. Optimization of o tratamento of anxiety disorders with selank. Zhurnal Nevrologii i Psikhiatrii. 2015;115(6):33–40.
- U.S. Food and Drug Administration. Substancia Farmaceutica a Granels Used in Compounding Under Section 503B. FDA Compounding Database. 2023.
- Zozulya AA, Neznamov GG, Syunyakov TS, et al. Efficacy and possible mechanisms of action of a novo(a) peptide anxiolytic selank no(a) therapy of generalized anxiety disorders and neurasthenia. Zhurnal Nevropatologii i Psikhiatrii. 2008;108(4):38–48.
- Kozlovskii II, Danchev ND. The optimizing action do(a) synthetic peptide Selank on a conditioned ativo(a) avoidance reflex in rats. Neuroscience and Behavioral Physiology. 2003;33(7):639–643.
- Kolomin TA, Agapova T, Agniullin YV, et al. Changes no(a) Transcription Profile do(a) Hippocampus in Response to Administration do(a) Tuftsin Analog Selank. Neuroscience and Behavioral Physiology. 2014;44(8):849–855.
- V'yunova TV, Andreeva LA, Shevchenko KV, et al. Peptide regulacao of specific ligand-receptor interactions of GABA com o(a) plasma membranes of nerve cells. Neurochemical Journal. 2014;8(4):259–264.
- Volkova A, Shadrina M, Kolomin T, et al. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Frontiers in Pharmacology. 2016;7:31.
- Kost NV, Sokolov OY, Gabaeva MV, et al. Semax and Selank Inhibit the Enkephalin-Degrading Enzymes of Human Serum. Russian Journal of Bioorganic Chemistry. 2001;27(3):180–183.
- Zozulya AA, Kost NV, Sokolov OY, et al. The Inhibitory Effect of Selank on Enkephalin-Degrading Enzymes como um(a) Possible Mechanism of Its Anxiolytic Activity. Bull Exp Biol Med. 2001;131(4):315–317.
- Inozemtseva LS, Karpenko EA, Dolotov OV, et al. Intranasal administration of o peptideo Selank regula BDNF expression no(a) rat hippocampus in vivo. Doklady Biological Sciences. 2008;421:241–243.
- Narkevich VB, Kudrin VS, Klodt PM, et al. Effects of Selank on monoamine neurotransmitters no(a) brain of BALB/c and C57BL/6 mice. Bull Exp Biol Med. 2008;145(1):68–71.
- Uchakina ON, Uchakin PN, Miasoedov NF, et al. Immunomodulatory effects of selank in patients with anxiety-asthenic disorders. Zhurnal Nevrologii i Psikhiatrii. 2008;108(5):71–75.
- Kozlovskii II, Andreeva LA, Kozlovskaya MM. The role do(a) endogenous opioid system no(a) anxiolytic action of Selank. Bull Exp Biol Med. 2012;153(5):728–730.
- Kolik LG, Nadorova AV, Kozlovskaya MM. Efficacy of Peptide Anxiolytic Selank during Modeling of Withdrawal Syndrome in Rats with Stable Alcoholic Motivation. Bull Exp Biol Med. 2014;157(1):61–65.
- Konstantinopolsky MA, Kolik LG, Chernyakova IV. Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats. Bull Exp Biol Med. 2022;173(6):730–733.
- Mukhina AY, et al. Effects of Selank on intestinal microbiota and stress-induziu changes. Russian Journal of Physiology. 2019/2020.
- Kasian A, Kolomin T, Andreeva L, et al. Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats. Behavioural Neurology. 2017;2017:5091027.
- Kolik LG, Nadorova AV, Antipova TA, Durnev AD. Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content. Bull Exp Biol Med. 2019;167(5):641–644.
- Medvedev VE, Tereshchenko ON, Israelian AI, et al. A comparison do(a) anxiolytic effect and tolerability of selank and phenazepam. Zhurnal Nevrologii i Psikhiatrii. 2014;114(7):17–22.
- Semenova TP, Kozlovskii II, Zakharova NM, Kozlovskaya MM. Experimental optimization of learning and memory processes by selank. Eksperimental'naia i Klinicheskaia Farmakologiia. 2010;73(8):2–5.
- Filatova E, Kasian A, Kolomin T, et al. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells. Frontiers in Pharmacology. 2017;8:89.
- Kolomin TA, Shadrina M, Andreeva LA, et al. Expression of inflamacao-related genes in mouse spleen under tuftsin analog Selank. Regulatory Peptides. 2011;170(1-3):18–23.
- Andreeva LA, Nagaev IY, Mezentseva MV, et al. Antiviral properties of structural fragments of o peptideo Selank. Doklady Biological Sciences. 2010;431:79–82.
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Este conteudo e fornecido apenas para fins educacionais e informativos. Os produtos sao fornecidos apenas para estudos in vitro e nao sao medicamentos, drogas ou suplementos. Nao aprovado pela FDA para prevenir, tratar ou curar qualquer condicao.