Semax [Spray]

What is Semax?

Semax (MEHFPGP) is a synthetic heptapeptide structurally derived from the adrenocorticotropic hormone (ACTH) fragment 4–10, extended with a C-terminal Pro-Gly-Pro (PGP) sequence. It was originally developed at the Institute of Molecular Genetics of the Russian Academy of Sciences as a stable, non-hormonal analog of ACTH that retains central nervous system activity without the adrenal stimulatory properties of the parent hormone.

Chemically, Semax is classified as a neuropeptide and melanocortin analog. Its sequence (Met-Glu-His-Phe-Pro-Gly-Pro) lacks the steroidogenic activity characteristic of full-length ACTH, making it an object of neurobiological investigation. Research interest has centered on its reported interactions with melanocortin receptor subtypes and its modulatory effects on neurotrophin expression in rodent central nervous system models.

Semax is not approved by the Food and Drug Administration (FDA) for any human therapeutic application. It is not a dietary supplement or consumer product. It is intended exclusively for laboratory and research purposes.

All preclinical studies referenced in this document were conducted under institutional oversight consistent with IRB, IACUC, and AWA guidelines. Semax Nasal Spray is supplied by RCDbio exclusively for use under equivalent institutional research compliance frameworks.

Chemical Properties

How Does Semax Nasal Spray Work?

Melanocortin Receptor Interaction. Mechanistically, Semax has been investigated as a modulator of melanocortin receptor subtypes in in vitro and in vivo preclinical systems. Semax has been proposed in some preclinical literature to interact with melanocortin receptor subtypes, with some in vitro preparations suggesting affinity at MC4 and MC5. The precise binding mode — agonism, partial agonism, or antagonism — has not been definitively established across experimental systems, and published receptor binding characterization data for Semax remain limited. MC4 receptor engagement has been linked in the broader melanocortin literature to neurite outgrowth signaling, cognitive function modulation, and inflammatory response attenuation in astrocyte preparations. The full mechanistic characterization of Semax's interaction profile at melanocortin receptor subtypes remains an active area of preclinical investigation.

BDNF/TrkB Pathway Modulation. In rodent hippocampal preparations, Semax exposure has been associated with upregulation of brain-derived neurotrophic factor (BDNF) at both the protein and mRNA level. Specifically, intranasal administration in rat models has been observed to produce increases in BDNF protein expression, tyrosine phosphorylation of TrkB receptors (the high-affinity BDNF receptor), and transcriptional upregulation of BDNF exon III and TrkB mRNA in hippocampal tissue. These observations suggest that Semax Nasal Spray may modulate neurotrophic signaling through TrkB receptor activation in hippocampal neuronal preparations, though the precise upstream mechanism linking melanocortin receptor interaction to BDNF transcriptional changes has not been fully delineated.

C-Terminal PGP Contribution. The Pro-Gly-Pro (PGP) C-terminal extension of Semax has been independently investigated in ischemia-reperfusion models. Data suggest the PGP tripeptide may activate neurotrophin gene transcription in ischemic brain tissue preparations, indicating that this structural element contributes pharmacologically to the compound's observed activity profile and is not merely a metabolic stabilization moiety.

Neuroinflammatory Gene Expression Modulation. In rat models of focal cerebral ischemia (permanent middle cerebral artery occlusion), Semax has been observed to modulate the transcription of genes associated with immune and vascular system function. Genome-wide transcriptomic analyses in rodent ischemia models have identified Semax-induced suppression of proinflammatory cytokine mRNA (including Il1a, Il1b, Il6, Ccl3, and Cxcl2), alongside activation of neurotransmitter-associated gene expression. At the protein level, changes in CREB activation, MMP-9, c-Fos, and JNK expression profiles have been reported following Semax exposure in tMCAO rodent preparations.

Key Research Findings

These findings are derived exclusively from preclinical in vitro and in vivo animal studies. Data from human subjects is limited. Findings are not consistent across all models. This section does not constitute clinical evidence.

• BDNF/TrkB upregulation: Intranasal Semax exposure in rat hippocampal preparations observed to produce up to a 1.4-fold increase in BDNF protein and 1.6-fold increase in TrkB tyrosine phosphorylation levels. [Dolotov et al., 2006; PMID: 16996037]

• Proinflammatory gene suppression: In rat tMCAO ischemia models, Semax exposure is associated with statistically significant reductions in Il1a, Il1b, Il6, Ccl3, and Cxcl2 mRNA expression following ischemia-reperfusion induction. [Filippenkov et al., 2021; PMID: 34201112]

• Neuroprotective protein expression: Semax administration in cerebral ischemia-reperfusion rodent models associated with CREB upregulation in subcortical structures and downregulation of MMP-9, c-Fos, and JNK in adjacent cortical tissue. [Filippenkov et al., 2021; PMID: 34201112]

• Transcriptomic immunomodulation: Genome-wide RNA-Seq analysis in pMCAO rodent models observed Semax predominantly enhancing expression of immune-related gene networks, particularly chemokine and immunoglobulin-encoding genes, at 24 h post-occlusion. [Medvedeva et al., 2014; PMID: 24661604]

• Melanocortin receptor interaction: Semax has been investigated in preclinical preparations for interactions at melanocortin receptor subtypes; mechanistic characterization data remain limited and are not consistent across experimental systems.

What Are the Potential Research Applications of Semax?

Semax Nasal Spray is investigated in preclinical research contexts encompassing the following areas:

• Neurotrophin signaling research: In vitro and in vivo model systems examining BDNF/TrkB pathway dynamics, hippocampal neurotrophin expression, and the downstream consequences of TrkB receptor activation in neuronal cell preparations.

• Melanocortin receptor pharmacology: Receptor competition and binding assays investigating MC4 and MC5 receptor interaction profiles, competitive antagonism mechanisms, and downstream cAMP/adenylyl cyclase signaling.

• Cerebral ischemia-reperfusion models: Rodent tMCAO and pMCAO model systems examining peptide-mediated transcriptomic responses, proinflammatory cytokine suppression, and neuroprotective protein expression patterns.

• Neuroinflammatory pathway investigation: Cell culture and in vivo systems studying peptide modulation of astrocytic and microglial inflammatory mediator expression.

• Neuropeptide delivery pharmacokinetics: Intranasal administration models examining blood-brain barrier penetration, regional brain distribution, and CNS bioavailability of melanocortin-class peptides via the nasal route.

What Are the Potential Side Effects of Semax?

The following observations are derived exclusively from preclinical animal studies. No human clinical safety data has been established for Semax as a research compound.

In rodent models, high-dose Semax exposure has been generally associated with low acute toxicity profiles; no LD50 data in commonly used laboratory rodent species is available in peer-reviewed public literature as of the date of this publication.

Autonomic effects observed in some rodent preparations include transient changes in cortical nitric oxide (NO) production at doses used in global ischemia models (0.3 mg/kg in rat preparations).

No chronic toxicity data in any species has been established. Long-term safety, organ-level toxicity, reproductive toxicity, and genotoxicity data are absent from the peer-reviewed literature.

Immunomodulatory activity observed in transcriptomic studies indicates potential off-target effects on immune cell gene expression in ischemic tissue preparations; the implications of these gene-level changes in non-ischemic systems remain uncharacterized.

Data remains limited. Findings are not consistent across all models.

Risk & Handling

Handling Precautions

Semax Nasal Spray is intended for use by trained laboratory personnel only. The following precautions apply during all handling operations:

• Personal protective equipment (PPE) required: nitrile gloves, laboratory coat, and eye protection at minimum.

• Nasal spray solution should be handled in a clean laboratory environment; avoid aerosol generation during manipulation or transfer of reconstituted solutions.

• Pipetting and aliquoting should be performed with calibrated laboratory equipment; avoid contact with mucous membranes, eyes, or skin during handling.

• Dispose of all biological waste and spent solutions in accordance with institutional biosafety protocols and applicable local regulations.

Exposure Risks

Risk Tier: MODERATE

Semax is a biologically active synthetic peptide with demonstrated activity at melanocortin receptor subtypes and modulation of neurotrophin expression in CNS-relevant cell systems. No human safety data has been established. Acute toxicity data in preclinical species is limited; no LD50 data is publicly available in peer-reviewed literature. The compound's CNS-active profile warrants handling caution consistent with a MODERATE biological hazard tier. Chronic toxicity, reproductive toxicity, and genotoxicity have not been investigated.

Storage

• Lyophilized: Store at −20°C in a desiccated, airtight container protected from light and moisture. Stable for up to 24 months under these conditions.

• Reconstituted / Nasal Spray: Maintain at 2–8°C. Use within 28 days of preparation. Do not freeze the reconstituted solution. Protect from direct light exposure.

• Freeze-thaw: Repeated freeze-thaw cycling of the lyophilized powder is not recommended and may reduce peptide integrity. Aliquot prior to first use to minimize freeze-thaw exposure.

• Supplied in sterile, sealed amber glass or HDPE spray container as appropriate to preserve photostability.

FAQs

Q1: What is the reported plasma half-life of Semax in preclinical research models?
Semax is a relatively short-lived peptide in plasma; enzymatic degradation by enkephalinase and other proteases has been proposed as a clearance pathway in preclinical pharmacokinetic studies. Precise plasma half-life values vary by species, route, and preparation. The PGP C-terminal extension has been reported to confer some resistance to proteolytic degradation relative to the parent ACTH(4-10) fragment, though definitive half-life data from standardized laboratory models remain limited in publicly available literature. All pharmacokinetic data referenced is from preclinical animal studies; no human pharmacokinetic data has been established.

Q2: What is the recommended storage duration for the Semax Nasal Spray research solution?
Reconstituted Semax nasal spray solution should be stored at 2–8°C and used within 28 days of preparation. Lyophilized peptide stock should be maintained at −20°C, desiccated and protected from light, where it is stable for up to 24 months from the manufacturing date when stored correctly.

Q3: Is Semax stable after reconstitution?
Reconstituted peptide solutions are susceptible to degradation via hydrolysis and proteolytic activity over time. Stability is optimized by storing at 2–8°C in a sealed container protected from light. Repeated warming and cooling of the reconstituted solution should be avoided. Addition of bacteriostatic agents (e.g., benzyl alcohol) per institutional protocols may extend working solution stability; researchers should validate stability under their specific laboratory conditions.

Q4: What preclinical toxicity observations have been reported for Semax?
Available preclinical data from rodent in vivo studies indicate a generally low acute toxicity profile at doses used in neuroprotection research (0.15 – 0.5 mg/kg in rodent preparations). No LD50 data is available in peer-reviewed literature. Chronic toxicity, genotoxicity, reproductive toxicity, and organ-specific toxicity data are absent from the published record. No human safety data has been established.

Q5: Does Semax interact with opioid receptor systems?
Semax has been proposed in some preclinical literature to interact with enkephalin-degrading enzymes (enkephalinase inhibition), which could indirectly modulate endogenous opioid tone in in vitro systems. Direct binding to classical opioid receptors (MOR, KOR, DOR) has not been established in peer-reviewed receptor characterization studies. The mechanism of enkephalinase interaction, if present, remains incompletely characterized.

Q6: Is the Semax Nasal Spray formulation suitable for cell culture work?
The nasal spray formulation contains the active peptide in an aqueous buffered vehicle. Researchers intending to use the preparation in cell culture applications should verify excipient compatibility with their specific cell system. For highly sensitive cell preparations, it is advisable to confirm buffer composition from the Certificate of Analysis (COA) and assess potential cytotoxicity of excipients under their laboratory conditions. Visit RCD Bio to explore our full research compound catalog.