Semax [Nasal Spray]

Description

What is Semax?

Semax is a synthetic heptapeptide structurally based on the ACTH(4–7) tetrapeptide (Met-Glu-His-Phe), extended at the C-terminus with a Pro-Gly-Pro (PGP) stabilisation sequence, making it an analogue of ACTH(4–10) in which the native Arg-Trp-Gly residues at positions 8–10 are replaced by Pro-Gly-Pro to eliminate steroidogenic activity and enhance metabolic stability. The compound’s sequence (Met-Glu-His-Phe-Pro-Gly-Pro; MEHFPGP) carries neither the free N-terminal modification present in N-Acetyl Semax nor the C-terminal amide present in the amidate forms — making it the parent compound in the Semax analogue family from which all terminal-modified derivatives are derived. Semax was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences as a stable, non-hormonal CNS-active melanocortin analogue designed to retain neurological activity without the adrenal-stimulatory properties of full-length ACTH.

Semax has been approved as a registered pharmaceutical in Russia since 1996 for clinical indications including post-stroke recovery, optic nerve atrophy, and cognitive impairment, and is on the Russian List of Vital and Essential Drugs approved by the Russian Federation government on 7 December 2011. It is available in Russia as a 0.1% nasal drop formulation. Despite this approval, Semax has not been evaluated or approved by the United States Food and Drug Administration or the European Medicines Agency for any indication. Research-grade Semax from RCDbio is not a pharmaceutical product and is not approved for any use outside laboratory research contexts.

Semax’s primary investigated pharmacological activities in preclinical models include upregulation of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor TrkB in hippocampal tissue, modulation of dopaminergic and serotonergic neurotransmitter systems, suppression of neuroinflammatory gene expression in cerebral ischaemia-reperfusion rodent models, and melanocortin receptor interactions at MC4 and MC5 subtypes. It is not a dietary supplement and is not intended for human consumption or therapeutic self-administration. All RCDbio research compounds are supplied strictly for laboratory and research purposes only.

Chemical Properties

Property	Detail
Product Type	Synthetic Heptapeptide / Melanocortin Analogue (ACTH(4-7)/PGP) Research Compound
Product Name	Semax
Application	Scientific / Research Use Only
CAS Number	80714-61-0
Molar Mass	813.93 g/mol
Chemical Formula	C37H51N9O10S
PubChem CID	122178
IUPAC Name	(2S)-1-[2-{[(2S)-1-[(2S)-2-{[2-{[(2S)-2-{[(2S)-2-amino-4-methylsulfanylbutanoyl]amino}-4-carboxybutanoyl]amino}-3-(1H-imidazol-5-yl)propanoyl]amino}-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino}acetyl]pyrrolidine-2-carboxylic acid
Amino Acid Sequence	Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP); 7 amino acids; free N-terminus; free C-terminus
Structural Origin	Based on ACTH(4–7) tetrapeptide (Met-Glu-His-Phe) + C-terminal Pro-Gly-Pro extension; analogue of ACTH(4–10) with native positions 8–10 (Arg-Trp-Gly) replaced by Pro-Gly-Pro
Semax Analogue Family	Semax (no modification) → N-Acetyl Semax (N-terminal acetyl) → Semax Amidate (C-terminal amide) → N-Acetyl Semax Amidate (both modifications) → Adamax (N-acetyl + adamantyl C-terminus)
Synonyms	MEHFPGP; H-Met-Glu-His-Phe-Pro-Gly-Pro-OH; ACTH(4-7)PGP; (Pro⁸,Gly⁹,Pro¹⁰)ACTH-(4-10)
Pharmaceutical Status	Approved pharmaceutical in Russia since 1996 (0.1% nasal drop). Not FDA or EMA approved. Research-grade material from RCDbio is not a pharmaceutical product.
Physical Form	Lyophilized white to off-white powder
Solubility	Freely soluble in water; soluble in PBS and aqueous buffers
Storage (Lyophilized)	−20°C; sealed container; protected from light and moisture
Storage (Reconstituted)	4°C; use within 48–72 hours; avoid repeated freeze-thaw cycles
Purity	≥98% (HPLC verified, independent third-party laboratory analysis)
WADA Status	Semax is not explicitly named on the 2026 WADA Prohibited List. As a non-approved research-grade peptide outside its Russian pharmaceutical approval context, S0 (Non-Approved Substances) provisions may apply in sport-adjacent research contexts. Verify at GlobalDRO.com prior to use.

How Does Semax Work?

Semax has been investigated in preclinical and clinical research systems for interactions across several distinct molecular pathways. Its mechanism of action involves melanocortin receptor modulation, BDNF/TrkB neurotrophin signalling, monoaminergic neurotransmitter system interactions, and neuroinflammatory gene expression modulation.

Melanocortin Receptor Interaction

Semax has been investigated as a modulator of melanocortin receptor subtypes in preclinical in vitro and in vivo systems. The compound has been proposed to interact with MC4 and MC5 receptor subtypes in some preclinical literature; however, the precise binding mode — agonism, partial agonism, or allosteric modulation — has not been definitively established across all experimental systems. MC3 receptor antagonism was not observed in assay preparations, and MC1/MC2 receptor interactions have not been fully characterised. The ACTH(4–7) core of Semax lacks the essential melanocortin receptor-activating His-Phe-Arg-Trp pharmacophore present in full-length ACTH; its melanocortin receptor interaction profile is therefore pharmacologically distinct from parent ACTH and from selective MC receptor agonists.

BDNF/TrkB Pathway Modulation

In rodent hippocampal preparations, intranasal Semax administration has been associated with upregulation of brain-derived neurotrophic factor (BDNF) at both mRNA and protein levels, alongside tyrosine phosphorylation of TrkB — BDNF’s high-affinity receptor. Specifically, Semax exposure in rat models was associated with up to 1.4-fold increases in BDNF protein and 1.6-fold increases in TrkB tyrosine phosphorylation in hippocampal tissue preparations at specific dose and time-point conditions [Dolotov et al., 2006]. The upstream mechanism linking melanocortin receptor interaction to BDNF transcriptional upregulation has not been fully delineated. The PGP C-terminal extension of Semax has been independently proposed to contribute to neurotrophin gene transcription activation, particularly in ischaemic brain tissue models.

Dopaminergic and Serotonergic System Modulation

In rodent neurochemical studies employing in vivo microdialysis and HPLC measurement, Semax (0.15 mg/kg, IP) produced significant increases in striatal 5-HIAA concentrations (+25% tissue content at 2 hours; extracellular 5-HIAA increasing to 180% within 1–4 hours), indicating enhanced serotonin turnover in the striatum [Eremin et al., 2005]. The compound also potentiated amphetamine-induced dopamine release in the striatum when administered prior to D-amphetamine challenge, without itself directly altering tissue dopamine concentrations — suggesting a modulatory rather than direct dopaminergic mechanism.

Neuroinflammatory Gene Expression Modulation

In rodent tMCAO and pMCAO ischaemia-reperfusion model preparations, Semax has been associated with suppression of proinflammatory cytokine mRNA transcripts — including Il1a, Il1b, Il6, Ccl3, and Cxcl2 — in cortical and subcortical tissue [Stavchansky et al., 2021]. At the protein level, Semax administration in ischaemia-reperfusion preparations was associated with CREB upregulation in subcortical structures and downregulation of MMP-9, c-Fos, and JNK in adjacent cortical tissue [Filippenkov et al., 2021]. Genome-wide RNA-Seq analysis in pMCAO rodent preparations identified Semax predominantly enhancing expression of immune-related gene networks, particularly chemokine and immunoglobulin-encoding genes, at 24 hours post-occlusion [Medvedeva et al., 2014].

Key Research Findings

In preclinical and limited clinical research contexts, Semax has been associated with the following observations:

• BDNF/TrkB upregulation: Up to 1.4-fold increase in BDNF protein and 1.6-fold increase in TrkB tyrosine phosphorylation in rat hippocampal preparations following intranasal Semax at specific dose and time-point conditions [Dolotov et al., 2006].
• Serotonergic modulation: Striatal 5-HIAA tissue content increased +25%, and extracellular 5-HIAA increased to 180% within 1–4 hours following Semax (0.15 mg/kg IP) in rodent microdialysis preparations [Eremin et al., 2005].
• Dopaminergic potentiation: Semax potentiated D-amphetamine-induced striatal dopamine release without directly altering basal dopamine concentrations in rodent preparations [Eremin et al., 2005].
• Neuroinflammatory mRNA suppression: Statistically significant reductions in Il1a, Il1b, Il6, Ccl3, Cxcl2 mRNA observed in rodent tMCAO ischaemia-reperfusion preparations [Stavchansky et al., 2021].
• Ischaemia-reperfusion protein expression: CREB upregulation and MMP-9/c-Fos/JNK downregulation at protein level in cortical and subcortical rodent ischaemia-reperfusion tissue preparations [Filippenkov et al., 2021].

All findings listed above are derived from preclinical in vitro and in vivo rodent model data. Clinical data pertains to the Russian-approved pharmaceutical formulation. No FDA-regulated clinical trial data have been established for research-grade Semax. These observations do not constitute evidence of efficacy or safety for research-grade material in any human condition or organism.

What are the Potential Research Applications of Semax?

In controlled laboratory environments, Semax has been investigated for the following research applications. These are observed in preclinical and in vitro contexts and do not constitute claims of efficacy or safety in any organism.

Neurotrophin Signalling and BDNF Pathway Research Semax is employed as a reference compound in studies characterising BDNF expression dynamics, TrkB receptor activation, and downstream neuroplasticity markers in rodent hippocampal preparations and isolated neuronal cell systems. Research examines the relationship between melanocortin receptor interaction and BDNF transcriptional regulation under normal and stress conditions.

Melanocortin Receptor Pharmacology In receptor binding, cAMP reporter, and competition assay systems, Semax is investigated for its interaction profile at MC4 and MC5 receptor subtypes. Research characterises binding mode, affinity, and downstream signalling consequences of Semax engagement at melanocortin receptors relative to selective MC receptor agonists and the parent ACTH sequence.

Cerebral Ischaemia-Reperfusion and Neuroinflammatory Research In rodent tMCAO and pMCAO model systems, Semax is employed to characterise proinflammatory cytokine mRNA suppression, neuroprotective protein expression profiles, and transcriptome-wide gene network changes under ischaemia-reperfusion conditions. Research examines Semax’s dual role in immune-related gene upregulation and proinflammatory mediator suppression.

Monoaminergic System Pathway Studies. In rodent in vivo microdialysis preparations and isolated brain tissue systems, Semax is employed to characterise its effects on striatal serotonin turnover, dopamine release dynamics, and monoamine metabolite concentrations. Research examines whether ACTH(4–7)-derived peptides constitute a pharmacological class with defined monoaminergic modulation profiles.

Comparative Semax Analogue SAR Studies Semax serves as the unmodified reference compound for the complete analogue series — N-Acetyl Semax, Semax Amidate, N-Acetyl Semax Amidate, Adamax — in SAR investigations characterising how progressive terminal modifications and structural additions alter stability, receptor affinity, CNS bioavailability, and downstream pathway activity profiles.

What are the Potential Side Effects of Semax?

The following observations are from preclinical rodent studies and limited Russian clinical data from the approved pharmaceutical formulation context.

• Generally low acute toxicity profile reported in rodent preclinical studies at doses used in neuroprotection research (0.15–0.5 mg/kg); no LD50 data available in peer-reviewed literature
• Transient changes in cortical nitric oxide (NO) production observed at doses used in global ischaemia rodent models (0.3 mg/kg)
• Immunomodulatory activity observed in transcriptomic studies — upregulation of chemokine and immunoglobulin-encoding gene networks alongside proinflammatory suppression — indicates complex immune system interactions in ischaemic tissue preparations
• No chronic toxicity, reproductive toxicity, or genotoxicity data available in the peer-reviewed literature
• No human safety or tolerability data have been established for research-grade Semax outside the Russian-approved pharmaceutical context. These observations should not be extrapolated to research-grade material or to human or animal outcomes.

Risk & Handling

Handling Precautions

Semax should only be handled by trained laboratory personnel. Appropriate PPE is required: nitrile gloves, laboratory coat, and eye protection at minimum. When working with lyophilized powder, use within a laminar flow cabinet. Avoid aerosol generation during reconstitution. The methionine residue at position 1 is susceptible to oxidative modification under aerobic conditions — minimise exposure to atmospheric oxygen during handling and storage.

Exposure Risks

Risk Tier: MODERATE

Semax is a pharmacologically active CNS peptide with characterised activity at melanocortin receptors and BDNF/TrkB, dopaminergic, and serotonergic systems. Accidental systemic exposure may produce CNS pharmacological effects in tissues expressing these targets. The compound has a generally low acute toxicity profile in preclinical preparations, but its multi-pathway CNS activity warrants handling with caution appropriate to a MODERATE biological hazard tier. No human safety or tolerability data has been established for research-grade Semax.

Storage

• Lyophilized form: Store at −20°C in original sealed, light-protected container with desiccant; stable for up to 24 months under these conditions
• Reconstituted form: Store at 4°C; use within 48–72 hours of reconstitution
• Do not subject to repeated freeze-thaw cycles; the Met1 residue oxidation risk increases with each cycle
• Protect from prolonged light and heat exposure
• Avoid storage conditions that may promote Met1 oxidation — consider nitrogen overlay for working solutions requiring extended storage

Frequently Asked Questions

Q: What is Semax and what is it investigated for in research? A: Semax (MEHFPGP) is a synthetic heptapeptide based on ACTH(4–7) with a C-terminal Pro-Gly-Pro extension, approved as a pharmaceutical in Russia since 1996. It is investigated in preclinical research contexts for BDNF/TrkB pathway modulation, melanocortin receptor interaction, monoaminergic neurotransmitter system effects, and neuroinflammatory gene expression modulation in cerebral ischaemia-reperfusion models. Research-grade Semax from RCDbio is not the pharmaceutical product and is intended strictly for laboratory research purposes.

Q: What is the correct structural description of Semax in relation to ACTH? A: Semax is correctly described as based on the ACTH(4–7) tetrapeptide (Met-Glu-His-Phe) with a C-terminal Pro-Gly-Pro extension — making it an analogue of ACTH(4–10) in which the native positions 8–10 residues (Arg-Trp-Gly) are replaced by Pro-Gly-Pro. It is not “ACTH(4–10) extended with PGP” — ACTH(4–10) already has its own positions 8–10. This distinction is important for accurate mechanistic interpretation and differentiates Semax from true ACTH(4–10) receptor pharmacology.

Q: Is Semax FDA-approved? A: No. Semax has been approved as a pharmaceutical in Russia since 1996 and is on the Russian List of Vital and Essential Drugs. It has not been evaluated or approved by the FDA or EMA for any indication. Research-grade Semax from RCDbio is not a pharmaceutical product.

Q: What dopaminergic and serotonergic effects has Semax demonstrated in preclinical models? A: In rodent in vivo microdialysis studies, Semax (0.15 mg/kg IP) significantly increased striatal 5-HIAA tissue content (+25%) and produced extracellular 5-HIAA increases to 180% within 1–4 hours, indicating enhanced serotonin turnover. The compound potentiated D-amphetamine-induced striatal dopamine release without directly altering basal dopamine concentrations — indicating a modulatory mechanism rather than direct dopamine release [Eremin et al., 2005]. These findings are from rodent in vivo preclinical preparations.

Q: How does Semax differ from its analogues N-Acetyl Semax and N-Acetyl Semax Amidate? A: Semax (H-MEHFPGP-OH) has free N-terminus and free C-terminus — the baseline compound with no terminal protection. N-Acetyl Semax (Ac-MEHFPGP-OH) adds N-terminal acetylation only, providing aminopeptidase resistance while leaving the C-terminus susceptible to carboxypeptidase. N-Acetyl Semax Amidate (Ac-MEHFPGP-NH2) adds both N-terminal acetylation and C-terminal amidation, providing dual-terminus exopeptidase protection. Each modification extends stability progressively; the base Semax compound is the primary reference for all analogues.

Q: How should research-grade Semax be stored? A: Lyophilized Semax should be stored at −20°C in a sealed, light-protected container with desiccant; stable for up to 24 months under these conditions. Once reconstituted, store at 4°C and use within 48–72 hours. The methionine residue at position 1 is susceptible to oxidative modification — minimise atmospheric oxygen exposure and avoid repeated freeze-thaw cycles.

Q: What toxicity observations have been reported for Semax in preclinical studies? A: Semax has demonstrated a generally low acute toxicity profile in rodent preclinical studies at research-relevant doses (0.15–0.5 mg/kg). No LD50 data is available in peer-reviewed literature. No chronic toxicity, genotoxicity, or reproductive toxicity data have been published. No human safety or tolerability data has been established for research-grade Semax. Observations should not be extrapolated to human or animal outcomes.

Related Research Compounds

Researchers investigating Semax may also be interested in the following compounds currently available for laboratory research at RCDbio:

• N-Acetyl Semax Amidate — The fully terminal-protected Semax analogue (Ac-MEHFPGP-NH2); investigated for enhanced metabolic stability through dual-terminus exopeptidase protection, serving as the high-stability reference in Semax analogue comparative pharmacokinetic research.
• Selank — A synthetic heptapeptide (TKPRPGP) developed by the same Russian institute as Semax; commonly investigated alongside Semax in comparative neuropeptide CNS pharmacology, GABAergic modulation, and BDNF pathway research.
• Adamax — A Semax-derived nonapet combining N-acetyl Semax with an Ala-Gly spacer and adamantyl C-terminal modification; investigated for enhanced CNS bioavailability and metabolic stability relative to parent Semax.

All products listed are for laboratory and research purposes only.

References

1. Dolotov, O. V., Karpenko, E. A., Inozemtseva, L. S., Seredenina, T. S., Levitskaya, N. G., Rozyczka, J., Dubynina, E. V., Novosadova, E. V., Andreeva, L. A., Alfeeva, L. Y., Kamensky, A. A., Grivennikov, I. A., Myasoedov, N. F., & Engele, J. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research, 1117(1), 54–60. https://pubmed.ncbi.nlm.nih.gov/16996037/

2. Eremin, K. O., Kudrin, V. S., Saransaari, P., Oja, S. S., Grivennikov, I. A., Myasoedov, N. F., & Rayevsky, K. S. (2005). Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochemical Research, 30(12), 1493–1500. https://pubmed.ncbi.nlm.nih.gov/16362768/

3. Stavchansky, V. V., Denisova, A. E., Filippenkov, I. B., Sudarkina, O. Y., Gubsky, L. V., Myasoedov, N. F., Limborska, S. A., & Dergunova, L. V. (2021). The Peptide Drug ACTH(4-7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain. Genes, 12(6), 867. https://pubmed.ncbi.nlm.nih.gov/34097675/

4. Filippenkov, I. B., Stavchansky, V. V., Denisova, A. E., Yuzhakov, V. V., Sevan’kaeva, L. E., Sudarkina, O. Y., Dmitrieva, V. G., Gubsky, L. V., Myasoedov, N. F., Limborska, S. A., & Dergunova, L. V. (2021). Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. International Journal of Molecular Sciences, 22(12), 6179. https://pubmed.ncbi.nlm.nih.gov/34201112/ 

Disclaimer

Semax is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

The Food and Drug Administration has not approved Semax for any indication. This product is not approved for human or veterinary use. Researchers must comply with all applicable local, state, and federal laws and regulations governing the purchase and use of research compounds. By purchasing, you agree to our Terms and Conditions. RCDbio reserves the right to refuse sales to unauthorized individuals.

ATTENTION: All RCDbio products are strictly for LABORATORY AND RESEARCH PURPOSES ONLY. They are not intended for human consumption, veterinary use, or any other non-research application. For queries, complaints, or support, contact support@rcdbio.co