This is a working overview of ACTH(4-10), written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-07-28. Anything still debated is marked as such rather than presented as settled.
The proposed mechanism centres on neurotrophic signalling rather than direct receptor activation. Semax is reported to increase expression of brain-derived neurotrophic factor and nerve growth factor in several brain regions, and to shift the balance between excitatory and inhibitory neurotransmitter systems. Interaction with melanocortin receptors has been suggested because of the parent ACTH fragment. Many of these findings come from rodent studies, and the extent to which they translate to human physiology remains an open question.
Scientific literature on semax is unevenly distributed. A substantial share of published work originates from a small number of laboratories in Russia, while independent replication elsewhere is limited. Human data consist mostly of small trials with short follow-up, and several reported outcomes rely on subjective rating scales. Questions about how much intact peptide reaches the central nervous system after nasal administration, and how long it persists there, are still unresolved. The compound is best described as an active research subject rather than a settled pharmacological agent.
Regulatory status varies sharply by country. Semax is registered for medical use in Russia, where it appears in formularies as a nasal solution, and it also holds registration in a small number of neighbouring states. It has no approval from the United States Food and Drug Administration or the European Medicines Agency, and it is not a scheduled controlled substance in most jurisdictions. Elsewhere it circulates mainly as laboratory material, so purity documentation comes from suppliers rather than from a national pharmacopoeia.
Semax is a synthetic peptide created in the Soviet Union during the early 1980s by researchers working in Moscow. It was built from the short adrenocorticotropic hormone fragment known as ACTH(4-10), and the chain was then extended with three additional amino acids. The resulting molecule was named semax and entered clinical use in Russia in 1994. It is generally described as a nootropic and neuroprotective agent rather than as a hormone analogue.
The parent fragment ACTH(4-10) carries the sequence Met-Glu-His-Phe-Arg-Trp-Gly. Semax replaces the arginine and tryptophan positions with a proline-glycine-proline tail, giving Met-Glu-His-Phe-Pro-Gly-Pro. That change removes residues associated with adrenal stimulation, so the peptide does not drive cortisol release the way full ACTH does. This distinction shapes how the compound is grouped in the literature, where it sits with neuropeptides and peptide neuromodulators rather than with corticosteroids.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C37H51N9O10S | Calculated for the free peptide |
| Molar mass | 813.9 g/mol | Anhydrous free base |
| Peptide class | Synthetic heptapeptide | ACTH(4-10) analogue |
| Parent fragment | ACTH(4-10) | Adrenocorticotropic hormone segment |
| Developmental origin | Institute of Molecular Genetics, Moscow | Work began in the 1980s |
The C-terminal Pro-Gly-Pro extension is not incidental. Proline-rich tails are known to resist several common peptidases, and the published literature attributes the longer half-life of Semax, relative to unmodified ACTH fragments, to this feature. The modification also removes the melanocyte-stimulating and corticosteroidogenic activity that characterizes longer ACTH-derived sequences. Because the molecule is small and hydrophilic, it is typically formulated as an aqueous solution for intranasal or parenteral delivery. Acetylation or amidation at the termini appears in closely related research peptides and shifts the mass by a fixed increment.
Reported pharmacological work centers on neurotrophic signaling, including changes in BDNF and NGF expression in hippocampal tissue in animal models. Human data come largely from studies conducted in Russia, and how well those results generalize to other populations remains an open question. Regulatory status differs sharply by jurisdiction: Semax is a registered prescription medicine in Russia, while it holds no approved marketing status in the United States or the European Union. Outside such jurisdictions it is generally handled as a research chemical, which affects both documentation and quality expectations.
Regulatory status differs sharply between jurisdictions. In Russia the peptide is registered as a prescription nasal preparation, while agencies such as the United States Food and Drug Administration have not approved it for any indication. Products sold elsewhere are typically labeled for laboratory research only, and such labels shift responsibility for safe handling to the purchaser. Because the same name covers pharmaceutical-grade nasal drops and bulk research powder, identity and purity documentation becomes the main practical concern when comparing sources.
Semax is a synthetic seven-amino-acid peptide whose sequence extends the ACTH(4-10) fragment with a C-terminal proline-glycine-proline tripeptide. The commonly cited sequence is Met-Glu-His-Phe-Pro-Gly-Pro, giving a molecular formula near C37H51N9O10S and a molecular weight close to 813.9 g/mol. It belongs to the broader class of synthetic ACTH fragments studied for central nervous system effects rather than for adrenal steroid stimulation. In practice the material appears as a lyophilized white powder for laboratory work or as a dilute saline solution in clinical settings.
=== Other dermatological conditions === In addition to the approved use for treating acne vulgaris, researchers have investigated off-label applications for dermatological conditions, such as rosacea, psoriasis, and other conditions. Rosacea was reported as responding favorably to doses lower than used for acne. Isotretinoin in combination with ultraviolet light was shown affective for treating psoriasis. Isotretinoin in combination with injected interferon-alpha showed some potential for treating genital warts. Isotretinoin in combination with topical fluorouracil or injected interferon-alpha showed some potential for treating precancerous skin lesions and skin cancer.
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==== MeSH D06.472.040 – adrenal cortex hormones ==== MeSH D06.472.040.502 – 17-ketosteroids MeSH D06.472.040.502.112 – androstenedione MeSH D06.472.040.502.195 – androsterone MeSH D06.472.040.502.497 – estrone MeSH D06.472.040.502.583 – etiocholanolone MeSH D06.472.040.502.620 – dehydroepiandrosterone MeSH D06.472.040.502.620.300 – dehydroepiandrosterone sulfate MeSH D06.472.040.585 – hydroxycorticosteroids MeSH D06.472.040.585.353 – 11-hydroxycorticosteroids MeSH D06.472.040.585.353.118 – aldosterone MeSH D06.472.040.585.353.237 – corticosterone MeSH D06.472.040.585.353.476 – hydrocortisone MeSH D06.472.040.585.353.500 – 18-hydroxycorticosterone MeSH D06.472.040.585.353.825 – tetrahydrocortisol MeSH D06.472.040.585.478 – 17-hydroxycorticosteroids MeSH D06.472.040.585.478.195 – cortisone MeSH D06.472.040.585.478.225 – cortodoxone MeSH D06.472.040.585.478.392 – hydrocortisone MeSH D06.472.040.585.478.782 – tetrahydrocortisol MeSH D06.472.040.585.478.865 – tetrahydrocortisone MeSH D06.472.040.585.611 – desoxycorticosterone MeSH D06.472.040.585.611.400 – 18-hydroxydesoxycorticosterone MeSH D06.472.040.585.745 – pregnenolone MeSH D06.472.040.585.745.500 – 17-alpha-hydroxypregnenolone
==== Phenylethylamine ==== In general, phenylethylamine consists of an aromatic ring connected to an amine group which is 2 carbons away. Each type of phenylethylamine differs by the substitutions at the alpha and beta carbon position. When a methyl group is attached at the alpha position, the compound becomes amphetamines which has the ability to modulate the 5HT-2A serotonin receptors. Eventually, the activated receptors cause hallucinations. To ensure sufficient binding, the agonists must contain a primary amine, methoxy group and hydrophobic functional groups.
Protein phosphatase 1 subunits PP1β and PP1γ have been shown to form functional complexes with OGT. A synthetic phosphopeptide was able to be dephosphorylated and O-GlcNAcylated by an OGT immunoprecipitate. This complex has been referred to as a "yin-yang complex" as it replaces a phosphate modification with an O-GlcNAc modification. PP1γ also exists in a heterotrimer with OGT and URI under high glucose conditions. MYPT1 is another protein phosphatase subunit that forms complexes with OGT and is itself O-GlcNAcylated. MYPT1 appears to have a role in directing OGT towards specific substrates.
Sources: en.wikipedia.org
Guidelines released by the Clinical Pharmacogenomics Implementation Consortium (CPIC) advise against administering codeine to ultrarapid metabolizers, where this genetic information is available. The CPIC also suggests that codeine use be avoided in poor metabolizers, due to its lack of efficacy in this group. Codeine and its salts are readily absorbed from the gastrointestinal tract, and ingestion of codeine phosphate produces peak plasma concentrations in about one hour. Plasma half life is between 3 and 4 hours, and oral/intramuscular analgesic potency ratio is approximately equal to 1:1.5. The most common conversion ratio, given on equianalgesia charts used in the United States, Canada, the UK, Republic of Ireland, the European Union, Russia and elsewhere as 130 mg IM equals 200 mg PO—both of which are equivalent to 10 mg of morphine sulphate IV and 60 mg of morphine sulphate PO. The salt:freebase ratio of the salts of both drugs in use are roughly equivalent, and do not generally make a clinical difference. Codeine is metabolised by O- and N-demethylation in the liver to morphine and norcodeine. Hydrocodone is also a metabolite of codeine in humans. Codeine and its metabolites are mostly removed from the body by the kidneys, primarily as conjugates with glucuronic acid. The active metabolites of codeine, notably morphine, exert their effects by binding to and activating the μ-opioid receptor. People that can metabolize codeine to an extensive degree could result in a 30 mg dose yielding 4 mg of morphine.
==== Cytochrome P450 modulation ==== It has been reported that bicalutamide may have the potential to inhibit the enzymes CYP3A4 and, to a lesser extent, CYP2C9, CYP2C19, and CYP2D6, based on in vitro research. However, no relevant inhibition of CYP3A4 has been observed in vivo with bicalutamide at a dose of 150 mg (using midazolam as a specific marker of CYP3A4 activity). In animals, bicalutamide has been found to be an inducer of certain cytochrome P450 enzymes. However, dosages of 150 mg/day or less have shown no evidence of this in humans. Bicalutamide has been identified as a strong CYP27A1 (cholesterol 27-hydroxylase) inhibitor in vitro. CYP27A1 converts cholesterol into 27-hydroxycholesterol, an oxysterol that has multiple biological functions including direct, tissue-specific activation of the ER (it has been characterized as a selective estrogen receptor modulator) and the liver X receptor. 27-Hydroxycholesterol has been found to increase ER-positive breast cancer cell growth via its estrogenic action, and hence, it has been proposed that bicalutamide and other CYP27A1 inhibitors may be effective as adjuvant therapies to aromatase inhibitors in the treatment of ER-positive breast cancer. In addition to CYP27A1, bicalutamide has been found to bind to and inhibit CYP46A1 (cholesterol 24-hydroxylase) in vitro, but this has yet to be assessed and confirmed in vivo.
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Spinal cord The part of the central nervous system housed within the vertebral column. It transmits signals between the brain and the rest of the body and controls reflexes. Split-brain A condition resulting from surgical severing of the corpus callosum, often performed to treat severe epilepsy. Reveals the functional specialization of brain hemispheres. Stellate cell A star-shaped neuron, often GABA-ergic, found in regions like the cerebellum and somatosensory cortex. Stiles–Crawford effect A phenomenon in visual perception where light rays entering the eye near the center of the pupil are more effective in eliciting a visual response than those entering near the edge. Striatum A major component of the basal ganglia, involved in movement, reward, and procedural learning. Composed of the caudate nucleus and putamen. Stroke A condition where poor blood flow to the brain results in cell death. Symptoms depend on the affected brain region and may include paralysis, speech impairment, and memory loss. Subarachnoid space The area between the arachnoid mater and the pia mater, filled with cerebrospinal fluid that cushions the brain and spinal cord. Substantia nigra A midbrain structure involved in movement and reward. Degeneration of dopaminergic neurons here leads to Parkinson's disease. Sulcus A groove on the surface of the cerebral cortex that separates adjacent gyri. Prominent sulci define major brain lobes and landmarks. Superior colliculus A structure in the midbrain involved in visual processing and control of eye movements. Part of the tectum.
Sources: en.wikipedia.org
Semax is based on the ACTH(4-10) fragment, a seven-amino-acid segment of adrenocorticotropic hormone. The synthetic peptide retains the core sequence while removing regions associated with endocrine activity. This modification is intended to isolate effects on the nervous system.
It is registered for clinical use in Russia and a few other countries, typically as a nasal drop formulation. It does not hold approval from the United States Food and Drug Administration or the European Medicines Agency. Outside those markets it is generally handled as a research chemical.
The compound was developed in Moscow and the earliest studies were conducted there, so the primary literature is largely in Russian-language journals. Translation and indexing have been incomplete, which limits access for outside researchers. Independent groups have since published some work, but the total volume remains modest.
Registered medical products are most often 0.1% nasal drops. Research suppliers ship lyophilized powder, usually in milligram quantities, which is dissolved before use. The active peptide is the same in both cases; presentation and excipients differ.