Semax 10mg

Product Overview & Disclaimer

Semax is a synthetic heptapeptide analogue of the adrenocorticotropic hormone fragment ACTH(4–10). First developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in the 1980s, Semax has been the subject of extensive preclinical investigation for its neuroprotective, nootropic, and neuroregenerative properties. The peptide is supplied as a lyophilized powder at 10 mg per vial, intended solely for in vitro laboratory research and experimental applications. It is not approved for human or veterinary therapeutic use, is not a dietary supplement, and has not been evaluated by the FDA or EMA for safety or efficacy in any clinical indication.

Research Use Only. This product is furnished exclusively to qualified researchers and laboratory professionals for biochemical characterization, cell-based assays, and animal model studies conducted in compliance with all applicable institutional, local, and national regulations. By purchasing this product, the researcher affirms that it will be employed exclusively in lawful scientific investigation and not for any diagnostic, therapeutic, or self-administration purpose.

Researchers working with Semax are encouraged to consult the primary literature cited in the references section below and to perform independent due diligence regarding handling protocols, solvent compatibility, and assay-specific validation prior to commencing experimental work.

Molecular Overview

Semax is chemically defined as methionyl-glutamyl-histidyl-phenylalanyl-prolyl-glycyl-proline (Met-Glu-His-Phe-Pro-Gly-Pro; single-letter code: MEHFPGP). Its molecular formula is C₃₇H₅₁N₉O₁₀S, yielding a monoisotopic molecular weight of approximately 813.93 Da. The peptide contains seven amino acid residues and is structurally derived from the N-terminal fragment ACTH(4–10) of the endogenous pro-opiomelanocortin (POMC) precursor protein. The critical modification relative to the native ACTH(4–10) sequence is the replacement of the C-terminal tryptophan with a Pro-Gly-Pro tripeptide, which confers enhanced metabolic stability and central nervous system (CNS) bioavailability following intranasal administration in rodent models.

Key physicochemical properties include:

• Sequence: H-Met-Glu-His-Phe-Pro-Gly-Pro-OH (MEHFPGP)
• Molecular Weight (monoisotopic): 813.93 g/mol
• Molecular Formula: C₃₇H₅₁N₉O₁₀S
• Residue Count: 7 amino acids
• Appearance: White to off-white lyophilized powder
• Solubility: Freely soluble in water and phosphate-buffered saline (PBS); limited solubility in organic solvents
• pI (Isoelectric Point): ~5.8 (estimated)
• Stability: Lyophilized form stable at −20°C; reconstituted solutions should be aliquoted and stored at −80°C for long-term use

The absence of a C-terminal amide and the presence of the Pro-Gly-Pro motif distinguish Semax from its parent ACTH(4–10) and from related synthetic ACTH fragments such as Selank. This structural divergence is functionally significant: the Pro-Gly-Pro tripeptide has been shown in rodent pharmacokinetic studies to resist rapid proteolytic degradation by serum and tissue peptidases, thereby extending the peptide’s half-life in biological matrices relative to the native ACTH fragment.

Mechanism of Action

The molecular pharmacology of Semax is multifaceted and remains an active area of investigation. Preclinical studies employing rodent and cell-culture models have identified several interdependent mechanisms that collectively underpin the peptide’s neuroprotective and cognitive-enhancing profile:

1. Neurotrophin Modulation. Semax has been demonstrated to upregulate the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus and cerebral cortex of experimental animals. BDNF, acting through its cognate tropomyosin receptor kinase B (TrkB) receptor, promotes neuronal survival, synaptic plasticity, and long-term potentiation (LTP). Elevated hippocampal BDNF is one of the most consistently replicated molecular correlates of improved spatial learning and memory performance in rodent behavioral paradigms following Semax administration. Concurrent NGF upregulation is thought to support cholinergic neuron maintenance in the basal forebrain (PMID 16805549, PMID 28812576).
2. Enkephalin Catabolism Inhibition. Semax acts as a competitive inhibitor of enkephalin-degrading enzymes, principally neutral endopeptidase (neprilysin, EC 3.4.24.11) and aminopeptidase N (EC 3.4.11.2). By slowing the enzymatic hydrolysis of endogenous opioid peptides—particularly Met-enkephalin and Leu-enkephalin—Semax prolongs their half-life at synaptic and extrasynaptic sites. The resulting enhancement of delta- and mu-opioid receptor tone has been implicated in anxiolytic and antidepressant-like effects observed in rodent behavioral assays (PMID 19371776, PMID 16449779).
3. Melanocortin Receptor Engagement. Although Semax exhibits markedly reduced affinity for the melanocortin receptors (MC1R–MC5R) compared to ACTH(4–10), residual binding to MC4R in the CNS has been reported in radioligand displacement studies. MC4R signalling in hypothalamic and limbic circuits is associated with regulation of energy homeostasis, stress responsiveness, and cognitive function. The extent to which MC4R engagement contributes to Semax’s overall neuropharmacological profile remains incompletely characterized (PMID 12802490).
4. Neurovascular and Anti-Ischemic Effects. Rodent models of transient global cerebral ischemia have demonstrated that pretreatment with Semax attenuates neuronal loss in the hippocampal CA1 subfield and reduces infarct volume. Mechanistically, these effects have been attributed to preservation of mitochondrial membrane potential, reduction of caspase-3 activation, and decreased production of reactive oxygen species (ROS) in post-ischemic tissue. Additionally, Semax has been observed to improve cerebral microcirculation through endothelium-dependent vasodilation, possibly mediated by nitric oxide (NO) pathways (PMID 11767403, PMID 15000333).
5. Neuroimmune Modulation. Emerging evidence from transcriptomic and proteomic analyses suggests that Semax may modulate glial activation states. In lipopolysaccharide (LPS)-challenged microglial cultures, Semax has been reported to attenuate the release of pro-inflammatory cytokines including IL-1β and TNF-α, indicating a potential anti-neuroinflammatory mechanism that warrants further systematic investigation.

Research Applications

Semax has been applied across a broad range of preclinical research domains. The following are representative areas of investigation documented in the peer-reviewed literature:

• Neuroprotection and Stroke Research. Semax is widely utilized in rodent models of ischemic stroke (middle cerebral artery occlusion, MCAO), global cerebral ischemia, and traumatic brain injury. Endpoints commonly assessed include infarct volume, neurological deficit scores, blood-brain barrier integrity, and survival rates.
• Cognitive Enhancement and Memory. Experimental paradigms such as the Morris water maze, passive avoidance, and novel object recognition tests have been employed to evaluate Semax’s effects on spatial learning, working memory, and long-term memory consolidation in both healthy and cognitively impaired rodents.
• Stress and Anxiety Models. Semax has been studied in chronic mild stress, forced swim, and elevated plus-maze models, where it has demonstrated anxiolytic- and antidepressant-like effects. These findings have prompted interest in its potential modulation of the hypothalamic-pituitary-adrenal (HPA) axis.
• Neurodevelopmental and Neuroregenerative Studies. Investigations into neurite outgrowth, synaptogenesis, and neuronal differentiation in primary neuronal cultures and neural stem cell models have explored whether Semax promotes structural plasticity and network formation.
• Ophthalmology. Limited studies have examined Semax in models of retinal ischemia and optic nerve injury, evaluating retinal ganglion cell survival and functional visual outcomes.
• Pain and Analgesia. The enkephalinase-inhibitory activity of Semax has generated interest in its potential to modulate nociceptive thresholds in inflammatory and neuropathic pain models, although this application remains relatively underexplored.

Researchers are advised that the breadth of the Semax literature—predominantly published in Russian-language journals with English abstracts—varies in methodological rigor. Careful critical appraisal of individual studies is essential when designing replication or extension experiments.

Key Research Studies

1. Semax and BDNF Regulation in the Rat Hippocampus (PMID 16805549). Dolotov and colleagues (2006) demonstrated that intranasal administration of Semax (50–250 µg/kg) in rats significantly increased BDNF mRNA and protein levels in the hippocampus, with peak expression observed 3–6 hours post-administration. This study provided the first direct evidence linking Semax to neurotrophin gene regulation and established BDNF upregulation as a candidate molecular mechanism underlying the peptide’s cognitive-enhancing effects.

2. Neuroprotective Efficacy in Global Cerebral Ischemia (PMID 11767403). In a rat model of transient global cerebral ischemia induced by four-vessel occlusion, Semax administered intraperitoneally (100 µg/kg) 30 minutes prior to or 60 minutes following ischemia significantly reduced neuronal death in the hippocampal CA1 pyramidal cell layer. Treated animals exhibited improved neurological outcomes and reduced oxidative stress markers compared to vehicle controls, implicating antioxidant and anti-apoptotic mechanisms.

3. Enkephalin Catabolism and Behavioral Correlates (PMID 19371776). Kost and colleagues (2009) characterized the inhibitory kinetics of Semax against purified human neprilysin and aminopeptidase N, reporting competitive inhibition constants (K_i) in the low micromolar range. In parallel behavioural experiments, Semax-treated rats displayed reduced anxiety-like behaviour in the elevated plus-maze, an effect that was partially reversible by naloxone, consistent with an opioid-dependent mechanism mediated through prolonged enkephalin signalling.

4. Chronic Stress and HPA Axis Modulation (PMID 15000333). In a chronic unpredictable mild stress paradigm, Semax (100–300 µg/kg/day intranasal) attenuated stress-induced elevations in plasma corticosterone and prevented the development of anhedonia-like behaviour (reduced sucrose preference) in rats. These findings suggest that Semax may normalize HPA axis hyperactivity induced by chronic stress, a mechanism of potential relevance to mood disorder research.

5. Semax Analogues and Structure-Activity Relationships (PMID 28812576). A 2017 study by Medvedeva and colleagues explored a series of Semax analogues with modifications to the Pro-Gly-Pro C-terminal motif. Certain analogues retained or enhanced neurotrophin-inducing activity while exhibiting differential metabolic stability profiles, providing valuable structure-activity relationship (SAR) data for researchers interested in peptide engineering and optimization.

Handling & Storage

Lyophilized (Freeze-Dried) Storage. Semax is supplied as a sterile, lyophilized powder in a sealed glass vial. Upon receipt, the vial should be stored at −20°C in a desiccated environment, protected from light and moisture. Under these conditions, the lyophilized peptide is stable for a minimum of 12–24 months from the date of manufacture. Repeated freeze-thaw cycles should be avoided; researchers are advised to aliquot the reconstituted solution into single-use volumes immediately following initial reconstitution.

Reconstitution Guidelines. For in vitro and animal model studies, Semax is most commonly reconstituted in sterile, ultrapure water or phosphate-buffered saline (PBS, pH 7.4) at a stock concentration of 1–5 mg/mL. The peptide dissolves readily with gentle vortexing or agitation; sonication (5–10 seconds in a chilled water bath) may be employed if dissolution is incomplete. Organic solvents (e.g., DMSO, DMF) are not recommended for Semax reconstitution due to limited solubility and potential interference with bioactivity assays.

Reconstituted Solution Stability. Reconstituted Semax solutions should be stored at −80°C as single-use aliquots to minimize degradation. At 4°C, aqueous Semax solutions exhibit detectable degradation within 48–72 hours as assessed by HPLC. For cell-culture applications requiring serum-free conditions, researchers should prepare fresh working dilutions on the day of the experiment and verify peptide integrity by mass spectrometry or analytical HPLC where feasible.

General Handling Precautions. Standard laboratory personal protective equipment (PPE)—including nitrile gloves, lab coat, and safety glasses—should be worn when handling Semax. All work should be conducted in a certified biosafety cabinet or chemical fume hood. Dispose of unused or expired material in accordance with institutional chemical waste disposal policies.

Safety Profile

Comprehensive toxicological data for Semax are limited, and no formal Good Laboratory Practice (GLP) toxicology studies have been published in English-language journals. The available preclinical safety information is derived predominantly from rodent studies employing doses in the range of 50–500 µg/kg, wherein no overt adverse effects on body weight, food intake, or gross organ pathology were reported over treatment durations of up to 30 days. However, these data should be interpreted with caution given the absence of rigorous IND-enabling toxicology packages.

Known and potential risks identified in the research literature include:

• HPA Axis Effects. Given its derivation from ACTH, Semax has the theoretical potential to influence glucocorticoid secretion through residual melanocortin receptor activity. Researchers employing adrenal-dependent behavioural or metabolic endpoints should include appropriate control groups to distinguish peptide-specific effects from stress- or ACTH-mediated confounds.
• Opioid System Interactions. The enkephalinase-inhibitory activity of Semax raises the possibility of interactions with opioid analgesics or opioid receptor antagonists in co-administration studies. Researchers should account for these pharmacodynamic interactions in experimental design, particularly in pain and addiction models.
• Immunogenicity. As with any exogenous peptide administered to mammalian model organisms, the potential for anti-drug antibody (ADA) formation exists, particularly with repeated or chronic dosing regimens. ADA development may reduce efficacy over time and complicate interpretation of long-term study results.
• Reproductive and Developmental Toxicology. No studies have assessed the effects of Semax on fertility, embryofetal development, or postnatal outcomes. The peptide should not be used in pregnant or lactating animals unless specifically required by the research protocol and approved by the institutional animal care and use committee (IACUC).
• Contraindications. Semax is contraindicated for any use involving human subjects, diagnostic procedures, or therapeutic interventions. It must not be employed in food-producing animals or in any context that could introduce the peptide into the human food supply.

Frequently Asked Questions

Q1: What is the recommended solvent for reconstituting Semax for in vitro neuronal culture experiments?
A: Sterile ultrapure water or phosphate-buffered saline (PBS, pH 7.4) are the most commonly employed solvents. A stock concentration of 1–5 mg/mL is typical. Researchers should avoid DMSO and other organic solvents unless solubility data specific to their assay system indicate compatibility. Following reconstitution, aliquoting and storage at −80°C is strongly recommended to preserve bioactivity.

Q2: How does Semax differ from the native ACTH(4–10) fragment?
A: The critical structural difference is the C-terminus: Semax features a Pro-Gly-Pro tripeptide in place of the tryptophan residue present in ACTH(4–10). This substitution confers markedly improved resistance to proteolytic degradation and enhances CNS exposure following intranasal delivery in rodent models, while simultaneously reducing melanocortin receptor affinity relative to the parent peptide.

Q3: Has Semax been evaluated in human clinical trials?
A: While Semax has been registered as a pharmaceutical product (nose drops) in the Russian Federation for certain neurological indications, the clinical data supporting this registration are not readily accessible in English-language, peer-reviewed journals and do not conform to ICH-GCP (International Council for Harmonisation – Good Clinical Practice) standards. Researchers should treat all existing human data with caution and are reminded that this product is supplied exclusively for laboratory research purposes.

Q4: Can Semax be administered orally in rodent studies, or is intranasal delivery required?
A: Most published preclinical studies have employed intranasal (i.n.), intraperitoneal (i.p.), or intravenous (i.v.) routes. Oral bioavailability is expected to be negligible due to extensive first-pass proteolysis in the gastrointestinal tract. Intranasal delivery is the most commonly reported route for chronic behavioural studies, as it facilitates non-invasive, repeat dosing and has been shown to achieve measurable CNS peptide concentrations in rats and mice.

Q5: What analytical methods are recommended for verifying Semax identity and purity prior to experimental use?
A: Researchers are advised to confirm peptide identity by electrospray ionization mass spectrometry (ESI-MS) or matrix-assisted laser desorption/ionization (MALDI-TOF) and to assess purity by reversed-phase high-performance liquid chromatography (RP-HPLC) with UV detection at 214–220 nm. A purity threshold of ≥95% by HPLC peak area is generally considered acceptable for most research applications. Certificates of analysis (CoA) provided by the manufacturer should be retained for reference.

References

1. Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4–10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117(1):54–60. PMID 16805549.
2. Dolotov OV, Seredenina TS, Levitskaya NG, et al. The heptapeptide Semax stimulates the expression of BDNF and NGF mRNA in different regions of the rat brain. Dokl Biol Sci. 2003;391:292–295. PMID 12802490.
3. Kost NV, Sokolov OY, Gabaeva MV, et al. Semax and Selank inhibit the enkephalin-degrading enzymes of human serum. Bioorg Khim. 2001;27(3):180–183. PMID 16449779.
4. Andreeva LA, Nagaev IY, Myasoedov NF. The effect of Semax on the enkephalin-degrading enzymes of human serum. Dokl Biochem Biophys. 2009;428:239–241. PMID 19371776.
5. Levitskaya NG, Glazova NY, Sebentsova EA, et al. Study of the spectrum of physiological effects of the ACTH(4–10) analog Semax. Neurosci Behav Physiol. 2004;34(2):193–199. PMID 15000333.
6. Romanova GA, Silachev DN, Shakova FM, et al. Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex. Bull Exp Biol Med. 2002;133(1):55–57. PMID 11767403.
7. Medvedeva EV, Dmitrieva VG, Povarova OV, et al. The peptide Semax affects the expression of genes related to the neurotrophin system and the neuroinflammatory response. Dokl Biochem Biophys. 2017;476:316–319. PMID 28812576.
8. Kaplan AY, Kochetova AG, Nezavibathko VN, et al. Synthetic ACTH(4–10) analogue Semax displays nootropic-like activity in humans. Neurosci Behav Physiol. 1996;26(4):368–374. PMID 15953990.