Selank / Semax

Selank and Semax are products of a peptide-design program at the Institute of Molecular Genetics, Russian Academy of Sciences. Each began as a short endogenous sequence — tuftsin (Thr-Lys-Pro-Arg) for Selank, and the ACTH(4-10)/ACTH(4-7) melanocortin fragment for Semax — extended with a C-terminal Pro-Gly-Pro (PGP) tripeptide. Reviews of the chemistry (Vyunova et al., 2018; Koroleva & Myasoedov, 2018) describe this 'glyproline' motif as the feature that slows enzymatic degradation and extends the duration of measurable biological activity, allowing intranasal administration in experimental work. Because the two molecules share a design origin, a stabilization strategy, and a common research field (the CNS), they are frequently catalogued and studied together even though they are pharmacologically distinct. PubChem indexes Selank as CID 11765600 (C33H57N11O9) and Semax as CID 9811102 (C37H51N9O10S).

The best-characterized strand of Selank literature examines its relationship to the GABAergic system. Vyunova et al. (2018) used radioligand–receptor ([³H]GABA binding) methods to characterize Selank as a concentration-dependent, subtype-selective positive allosteric modulator at GABA receptors, and examined how Selank can alter the modulatory activity of diazepam and olanzapine — suggesting partially overlapping but non-identical binding contexts. Gene-expression studies extended this picture: Volkova et al. (2016) measured changes in neurotransmission-related gene expression in rat frontal cortex after Selank administration. Filatova et al. (2017) applied an 84-gene GABAergic-neurotransmission panel to IMR-32 neuroblastoma cells, comparing the effects of GABA, Selank, and olanzapine in isolation and combination; they found that combined application of GABA and Selank altered the profile of genes that changed under GABA alone, a pattern consistent with an indirect or allosteric relationship rather than direct transcriptional action by Selank. Kasian et al. (2017) examined Selank together with diazepam in a rodent unpredictable chronic mild stress model using the elevated plus maze as a behavioral endpoint.

A second research line concerns Selank's effect on endogenous peptide-degrading enzymes. Kost et al. (2001) assayed enkephalin-degrading enzyme activity in human serum and demonstrated concentration-dependent inhibition by both Selank and Semax; their pentapeptide fragments also showed inhibition while shorter fragments did not, suggesting a scaffold-length requirement for the activity. Zozulya et al. (2001) examined Selank inhibition of plasma enkephalin hydrolysis in greater depth, framing the enzyme-inhibition finding as a candidate contributor to the behavioral profile observed in preclinical model systems. Reflecting Selank's tuftsin heritage, additional studies have examined cytokine and interferon modulation: Uchakina et al. (2008) studied cytokine and immunomodulatory markers in a study cohort examined for such measures, and Inozemtseva et al. (2008) measured BDNF expression in rat hippocampus after intranasal Selank administration. Clinical-study literature examining Selank in research cohorts characterized by anxiety-spectrum and neurasthenic features is represented by Zozulya et al. (2008) — a comparative study using Hamilton, Zung, and CGI psychometric scales alongside serum enkephalin activity measurement — and Medvedev et al. (2015), which examined study-design parameters in anxiety-disorder research participants.

The most-cited strand of Semax research concerns neurotrophin regulation. Dolotov et al. (2006, Brain Research) measured BDNF and TrkB mRNA and protein expression, including TrkB tyrosine phosphorylation status, in the rat hippocampus after a single intranasal administration. Semax is structured as an ACTH(4-10) analog that retains central melanocortin-receptor (MC3R/MC4R) interactions while lacking adrenal steroidogenic (MC2R) activity. Eremin et al. (2005) used striatal microdialysis to characterize dopaminergic and serotonergic neurochemical parameters — measuring tissue content and extracellular release of serotonin metabolites and examining the relationship of Semax administration to dopaminergic system activity. Inozemtseva et al. (2024) examined ACTH(4-10) analogs including Semax in a rodent chronic unpredictable stress model.

Semax is examined extensively in rodent cerebral-ischemia models. Medvedeva et al. (2014, BMC Genomics) performed a genome-wide transcriptional analysis (Illumina RatRef-12 BeadChip, ~22,226 genes) of ischemized rat cortex after permanent middle cerebral artery occlusion (pMCAO), characterizing which genes were altered by Semax at multiple post-occlusion time points; the affected gene cohort was distributed across immune and vascular functional categories. Reviews (Dergunova et al., 2023; Koroleva & Myasoedov, 2018) situate Semax within a broader melanocortin/neuroprotective-peptide research program. Gusev et al. (1997, 2018) reported clinical observational data examining Semax in stroke research cohorts, measuring electrophysiological and plasma BDNF endpoints as study outcomes.

Controlled co-administration literature examining Selank and Semax as a pair is sparse. The clearest example is Panikratova et al. (2020, Doklady Biological Sciences), a resting-state fMRI study in 52 research participants comparing Selank, Semax, and placebo conditions; the study measured between-group and between-condition differences in functional connectivity involving amygdala and temporal–parahippocampal regions. The two peptides are also mechanistically linked by the shared enkephalinase-inhibition finding from Kost et al. (2001), which assayed both in the same biochemical preparation. Beyond these, most pairing of the two peptides in the literature is narrative or catalogue framing rather than controlled co-administration research examining a defined endpoint.