Semax Guide: Effects, Dosing, and Research on the Nootropic Neuropeptide
Dr. Sieglinde Klaus
Scientific Editorial Team · Bergdorf Bioscience
Dr. Sieglinde Klaus
Scientific Editorial Team · Bergdorf Bioscience
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide and analog of the adrenocorticotropic hormone ACTH(4-10) that is gaining increasing importance in neuroscience research due to its nootropic, neuroprotective, and neurotrophic properties. Developed at the Moscow Institute of Molecular Genetics, the peptide activates melanocortin receptors (MC3/MC4) and upregulates the expression of BDNF, NGF, and TrkB, without producing the hormonal effects of the full ACTH molecule.
Semax was synthesized in the 1980s at the Institute of Molecular Genetics of the Russian Academy of Sciences as a therapeutic analog of ACTH(4-10). The research group around Myasoedov pursued the goal of preserving the cognitive effects of the natural ACTH fragment while eliminating the undesired hormonal actions. The result was a heptapeptide with the amino acid sequence Met-Glu-His-Phe-Pro-Gly-Pro, in which a C-terminal Pro-Gly-Pro tail substantially increases enzymatic stability compared to the natural ACTH(4-7) fragment Myasoedov et al., 1997. The peptide chain has a molecular weight of approximately 813 Da and presents as a white to cream-colored lyophilized powder that is freely soluble in water. In contrast to ACTH itself, Semax does not influence cortisol production or other adrenal steroids; the biological activity is limited to central mechanisms such as neurotrophin modulation and influences on the dopaminergic and serotonergic systems. This property makes Semax an interesting tool for fundamental research on cognition, neuroprotection, and synaptic plasticity.
The action of Semax is based on several molecular mechanisms running in parallel. First, the peptide binds specifically to receptors in the basal forebrain with a dissociation constant of 2.4 ± 1.0 nM; this binding is time-dependent, calcium-dependent, and reversible Dolotov et al., 2006. Second, Semax activates melanocortin receptors of the subtypes MC3 and MC4, which are expressed in the hippocampus, cortex, and hypothalamus and are involved in the regulation of learning processes, motivation, and neuroprotection. Third, the peptide demonstrably inhibits enkephalinases, by which endogenous opioid peptides are broken down more slowly. A particularly well-documented effect concerns the neurotransmitter system: in a study on rats, the tissue content of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum rose by 25 % two hours after Semax administration, and the extracellular 5-HIAA level increased within one to four hours to up to 180 % of the baseline value Eremin et al., 2005. Additionally, an increase in dopaminergic activity in the mesolimbic system was demonstrated; both neurotransmitter systems play a key role in cognitive processes and mood regulation.
The ability of Semax to upregulate the expression of neurotrophins is among the best-investigated properties of the peptide. Neurotrophins such as BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor) are key proteins for the survival of neurons, synaptic plasticity, and memory formation. After intranasal administration of Semax at a dose of 50 µg/kg in rats, a significant increase in BDNF protein concentration in the basal forebrain was measured within 30 minutes Dolotov et al., 2006. In parallel, Agapova and colleagues showed that Semax stimulates the gene expression of both BDNF and NGF in the hippocampus, frontal cortex, and retina in a time-dependent manner, with the maximum upregulation in the hippocampus reached after three hours Agapova et al., 2007. Particularly significant is the simultaneous activation of the TrkB receptor, the high-affinity receptor for BDNF, since only the co-expression of neurotrophin and receptor triggers an effective neuroprotective signaling cascade Dolotov et al., 2006. These results suggest that Semax coordinately activates the entire neurotrophin signaling network, which explains its neuroprotective properties at the molecular level.
The neuroprotective properties of Semax have been intensively studied in the context of cerebral ischemia, a research field with high clinical relevance. In a rat model with permanent occlusion of the middle cerebral artery (pMCAO), Semax enhanced the transcription of BDNF, TrkC, and TrkA three hours after occlusion, as well as NT-3 and NGF 24 hours after occlusion Shadrina et al., 2009. This temporally staggered activation of multiple neurotrophin genes suggests an orchestrated protective mechanism that addresses different phases of the ischemic cascade. At the transcriptome level, a comprehensive study by Filippenkov and colleagues showed that Semax, following ischemia-reperfusion, suppresses the expression of genes associated with inflammatory processes and simultaneously activates genes involved in neurotransmission Filippenkov et al., 2020. Specifically, a reduction of pro-inflammatory cytokines and an upregulation of genes for synaptic vesicle proteins were observed. It is notable that not only Semax itself, but also its main metabolite Pro-Gly-Pro (PGP) exerts neuroprotective transcriptional effects, suggesting an extended biological efficacy beyond the breakdown of the parent peptide.
The dosages described in the literature vary considerably depending on the research model and route of administration. In animal experiments, the standard dose range is 50 to 600 µg/kg intranasal; the majority of published studies on cognitive and neuroprotective effects use 50 µg/kg as the reference dose. In human studies on nootropic potential, dosages of 200 to 600 µg intranasal one to three times daily over periods of 10 to 14 days have been investigated Myasoedov et al., 1997. For acute indications such as ischemic stroke, significantly higher doses of 6 mg twice daily (12 mg total daily dose) intranasal were used in clinical studies, with treatment started within 6 to 12 hours of the event and continued over 5 to 10 days. Intranasal administration is the preferred route, as Semax reaches the rat brain via this path within two minutes; 0.093 % of the introduced radioactivity per gram of brain tissue was detected, of which 80 % belonged to the intact Semax molecule Glazova et al., 2006. Bergdorf Bio offers Semax as 10 mg vials, which allow precise dosing for various research protocols. Order Semax now
The pharmacokinetics of Semax are characterized by a rapid onset of action and a surprisingly long duration of effect, even though the plasma half-life of the peptide itself is only about 2 to 3 minutes. This apparent discrepancy is explained by rapid CNS penetration and the downstream activation of intracellular signaling cascades, which act far beyond the presence of the parent molecule. After intranasal administration, Semax reaches the brain within two minutes, with breakdown occurring mainly via peptidases and the tripeptide metabolite Pro-Gly-Pro being detected as the main breakdown product in biological samples Glazova et al., 2006. Despite the short half-life of the intact peptide, the functional effects on memory and attention last 20 to 24 hours; this is attributed to the long-lasting upregulation of BDNF and NGF, whose protein concentrations remain elevated for hours. Excretion occurs renally. For research practice, this pharmacokinetic profile means that a once- or twice-daily application can be sufficient to maintain constant neurotrophic effects throughout the investigation period. The high water solubility of the lyophilized powder facilitates reconstitution and the preparation of precise dilution series.
The proper storage and handling of Semax is crucial for preserving peptide integrity and the reproducibility of experimental results. Lyophilized Semax should be stored at 2 to 8 °C; for long-term storage over several months, a temperature of -20 °C or below is recommended. At room temperature, the lyophilized powder remains stable for approximately three weeks, which allows temperature-controlled shipping. The main breakdown pathways include the oxidation of the N-terminal methionine residue, hydrolysis of the peptide bond (especially at Pro-Gly bonds), and deamidation. Protective measures include storage under inert gas atmosphere (nitrogen or argon), the addition of antioxidants such as 0.1 % ascorbic acid in reconstituted solutions, and the use of metal-free buffers and containers. After reconstitution with bacteriostatic water, the solution is stable at 2 to 8 °C for approximately 30 days; for longer storage it should be frozen at -18 °C. Repeated freeze-thaw cycles should be avoided, as they significantly reduce peptide stability. The addition of excipients such as trehalose, mannitol, or glycerol (1 to 5 %) can improve the stability of reconstituted solutions during freeze-thaw cycles. Bergdorf Bio ships all Semax vials by cold-chain transport with seamless batch documentation and an accompanying Certificate of Analysis (CoA).
The purity of a research peptide is a critical quality parameter that directly influences the validity of experimental results. For reproducible research results with Semax, a purity of at least 98 % is recommended; Bergdorf Bio supplies Semax with an HPLC-verified purity of ≥99 %. Analysis is performed by reversed-phase HPLC (RP-HPLC), the gold standard for purity determination of synthetic peptides. Possible impurities include truncated sequences from solid-phase synthesis, deletion and insertion variants, and oxidation products of the N-terminal methionine. A Certificate of Analysis (CoA) should, in addition to the HPLC purity value, also contain the mass spectrum (MS) for confirmation of the correct molecular mass. When interpreting research results, it should be noted that even small impurities of 1 to 2 % may contain biologically active fragments that can distort the result; this applies in particular to studies on neurotrophin expression, in which even nanomolar concentrations trigger effects. Bergdorf Bio provides complete documentation with HPLC chromatogram and mass spectrum for each batch, which ensures cross-batch comparability. The GMP-compliant production and batch traceability make it possible to assign experimental results precisely to a specific production batch.
Semax is frequently discussed in the context of other neuropeptides, particularly Selank, another peptide developed at the Moscow Institute. While Semax is an ACTH(4-10) analog and acts primarily through melanocortin receptors and neurotrophin modulation, Selank is a tuftsin analog (Thr-Lys-Pro-Arg-Pro-Gly-Pro) that primarily develops anxiolytic and immunomodulatory effects through the endogenous opioid system and GABAergic mechanisms. Both peptides share the stabilizing C-terminal Pro-Gly-Pro tail. The most important difference lies in the primary action profile: Semax shows stronger nootropic and neuroprotective effects with pronounced BDNF upregulation, while Selank acts primarily as an anxiolytic and modulates the expression of GABA receptor subunits. In research practice, the peptides are used purposefully depending on the question: Semax for studies on cognition, neuroprotection, and synaptic plasticity; Selank for investigations on anxiety behavior and immune regulation. A combination of both peptides has been examined in some research protocols, but the available data are limited. The amino acid sequence, molecular weight (Semax: approx. 813 Da; Selank: approx. 751 Da), and receptor specificity differ fundamentally, which is why a direct substitution of one for the other in research protocols would not be appropriate.
The available research literature on Semax indicates a favorable safety profile, with the data primarily originating from animal studies and a limited number of human studies. In preclinical studies, rats showed no significant behavioral abnormalities or histopathological changes at doses of up to 600 µg/kg intranasal. The peptide influences neither the cortisol level nor other adrenal steroids, since it has no affinity for ACTH receptors in the adrenal gland. In human studies, no severe side effects were reported at the investigated dosages of 200 to 600 µg intranasal; occasionally, mild nasal irritation and transient headaches were documented Myasoedov et al., 1997. It is important to emphasize that long-term safety with repeated administration has not yet been comprehensively characterized, and the existing human studies predominantly originate from Russian literature, whose access and evaluation can be limited. Researchers should bear in mind when interpreting the safety data that most results were obtained in murine models and that a direct extrapolation to other species is not automatically justified. The peptide is intended exclusively for research purposes.
No. Semax is marketed exclusively as a research substance and is not intended for human consumption. In Russia, approved pharmaceutical formulations exist, but their regulatory status does not transfer to the EU or other jurisdictions.
Lyophilized Semax is reconstituted by slowly adding bacteriostatic water (0.9 % benzyl alcohol) to the inner wall of the vial. The solution should not be shaken but mixed by gentle swirling. After reconstitution, the peptide is stable at 2 to 8 °C for approximately 30 days.
The research literature contains protocols that use Semax in combination with Selank or other neuropeptides. Since interactions are not comprehensively characterized, every combination should be validated in a controlled experimental design.
All Semax vials are shipped by temperature-controlled cold-chain transport. From an order value of 250 €, shipping within the EU is free; the delivery time is 5 to 9 working days. Each shipment includes a Certificate of Analysis with HPLC purity value and mass spectrum.
Bergdorf Bio supplies Semax with ≥99 % HPLC-verified purity and complete batch documentation. Every batch is traceable, and the Certificate of Analysis includes HPLC chromatogram, mass spectrum, and details on the amino acid sequence.