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Background And Development — Evidence Review

By Editorial Desk · published 2026-02-28 · last reviewed 2026-03-15 · Wiki

This is a working overview of ACTH analog, written for readers who want more than a one-paragraph summary but less than a textbook.

Reviewed 2026-03-15. Anything still debated is marked as such rather than presented as settled.

Background and Development

Semax is a synthetic heptapeptide developed in the Soviet Union during the 1980s by researchers at the Institute of Molecular Genetics in Moscow. It was designed as a truncated analog of adrenocorticotropic hormone, retaining only the fragment spanning residues four through ten. Investigators sought a peptide that would preserve the cognitive effects associated with ACTH while eliminating the hormonal stimulation of the adrenal cortex. The compound entered clinical use in Russia during the following decade.

Russian regulatory authorities approved the peptide for nasal administration, and it remains listed in the national pharmacopoeia under several trade names. Documented indications include acute ischemic stroke, transient ischemic attacks, traumatic brain injury, and certain ophthalmological and neurological conditions. Physicians also prescribe it for cognitive complaints in older patients, although the evidence base for that use is thinner. Outside Russia and a few neighboring states, the substance is not an approved medicine and is sold instead as a research chemical.

Later generations of the molecule include an N-acetylated form and an amidated form, both marketed online alongside the parent peptide. These variants differ in terminal chemistry and stability, and they are frequently discussed in the same breath even though they have not been compared in controlled trials. Supply outside formal healthcare systems comes largely from laboratories that synthesize peptides to order. Purity and identity of these materials vary widely, and no single body oversees the international trade.

化学性质与分析表征

从分子层面看,Semax 是线性七肽,没有二硫键、糖基或脂链修饰,N 端为游离氨基,C 端为游离羧基。分子含组氨酸与谷氨酸侧链,因此在水和甲醇等极性溶剂中溶解良好,在非极性溶剂中溶解有限。计算分子量约为 814 Da,与其质子化离子的质荷比吻合,可用于质谱确认。

稳定性主要由水解与氧化两条路径支配。肽键在中性或弱酸性条件下相对稳定,遇到强碱或长时间高温则明显断裂;甲硫氨酸侧链容易被氧化成亚砜,使主峰前移并拉低实际含量。金属离子、光照和反复冻融会进一步促进降解或聚集。冻干粉在低温避光条件下可存放较长时间,配制后的水溶液通常需要冷藏并尽快用完。

Semax at a glance

PropertyValueNotes
Molecular classSynthetic heptapeptideAnalog of an ACTH fragment
Amino acid lengthSeven residuesMet-Glu-His-Phe-Pro-Gly-Pro
OriginMoscow, 1980sInstitute of Molecular Genetics
Approved regionsRussia and some neighboring statesNot cleared in Western markets
Common trade namesMultiple national brandsSold as a nasal formulation

Semax Background And Mechanism

Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. It was derived from the ACTH(4-10) fragment, a short segment of adrenocorticotropic hormone that lacks the hormonal activity associated with the full-length peptide. Researchers at the Institute of Molecular Genetics in Moscow developed the compound during the 1980s. It has been registered as a pharmaceutical product in Russia and several neighbouring countries, where it is supplied as a nasal solution, and it is also sold internationally as a research chemical.

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.

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Mechanism and Research Context

Published studies examine a fairly narrow set of endpoints. Rodent experiments commonly measure maze learning, infarct volume after induced ischemia, and tissue levels of neurotrophic factors. Clinical reports from Russian centres describe attention, memory and recovery scores in patients after stroke or transient ischemic attack. Most of those human studies are small and few have been repeated by independent groups. Outcome measures differ between studies, which limits direct comparison.

Circulation time for the peptide is short because peptidases cleave it readily. The Pro-Gly-Pro tail is thought to slow breakdown compared with the bare ACTH fragment, but the gain appears modest. Absorption after intranasal dosing is limited, and only a fraction of a dose is expected to reach the central nervous system. Laboratory concentrations therefore sit well above levels achieved systemically, a gap that complicates translation from bench findings to clinical claims.

Semax Peptide Structure and Origin

Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. Its design combines the ACTH(4-7) core fragment with a C-terminal Pro-Gly-Pro extension, a modification intended to improve stability and prolong activity. The molecule is hydrophilic, carries no lipid chains or glycosylation, and has a theoretical mass just over 810 daltons in its free form. All seven residues are proteinogenic amino acids, so no non-natural building blocks appear in the backbone. A free N-terminal methionine and C-terminal proline define the unmodified parent peptide.

The compound was developed during the 1980s at the Institute of Molecular Genetics in Moscow as part of research on fragments of adrenocorticotropic hormone. Early work examined short ACTH-derived sequences that retained neurotrophic effects while lacking the endocrine activity of the full hormone. Semax entered clinical use in Russia during the 1990s, where it received registration for several neurological indications. Outside that region it remained primarily a laboratory research material rather than an approved therapeutic. English-language literature on it grew more slowly and frequently cited the original Russian studies.

Terminology around the compound varies by source. It appears in catalogues and papers as Semax, as the heptapeptide ACTH(4-7)-Pro-Gly-Pro, and under various alphanumeric laboratory codes used by individual suppliers. These names refer to the same sequence but may imply different salt forms, purity grades, or counter-ions. Peptide databases usually list the free base mass, while product descriptions sometimes report acetate or trifluoroacetate salts with a different formula weight. Because naming conventions for research peptides are not standardised across vendors, checking the declared sequence and measured mass is more reliable than relying on a trade name alone.

Reference notes

=== APOA-I: A Possible Novel Biomarker for Metabolic Side Effects in First Episode Schizophrenia === The authors of this study sought to determine the effect on metabolism of the drug risperidone in schizophrenia patients. After discovering that risperidone did have negative metabolic side effects, they tested membrane proteins for glucose and lipid transport in control and experimental groups by MALDI-TOF and fingerprinting. Results showed altered fingerprints and therefore altered levels of folding in the proteins. So, they concluded that risperidone negatively effects glucose and lipid transport proteins in the cell membranes of patients.

== Clinical significance == CTGF is associated with wound healing and virtually all fibrotic pathology. It is thought that CTGF can cooperate with TGF-β to induce sustained fibrosis and to exacerbate extracellular matrix production in association with other fibrosis-inducing conditions. Overexpression of CTGF in fibroblasts promotes fibrosis in the dermis, kidney, and lung, and deletion of Ctgf in fibroblasts and smooth muscle cells greatly reduces bleomycin-induced skin fibrosis. In addition to fibrosis, aberrant CTGF expression is also associated with many types of malignancies, diabetic nephropathy and retinopathy, arthritis, and cardiovascular diseases. Several clinical trials are now ongoing that investigate the therapeutic value of targeting CTGF in fibrosis, diabetic nephropathy, and pancreatic cancer. CTGF (CCN2) has recently been implicated in mood disorders, notably in the postpartum period; these effects may be mediated by its effects on myelination

An acid dye is a dye that is typically applied to a textile at low pH. They are mainly used to dye wool, not cotton fabrics. Some acid dyes are used as food colorants, and some can be used to stain organelles for medical microscopy. Acid dyes are anionic, soluble in water and are essentially applied from acidic bath. They possess acidic groups, such as SO3H and COOH and are applied on wool, silk and nylon when an ionic bond is established between a protonated –NH2 group of the fibre and acid group of the dye. Overall wash fastness is poor, although lightfastness is quite good. As dye and fibre contain opposite electrical natures, strike rate and uptake of acid dye on these fibres is faster; electrolyte at higher concentration is added to retard dye uptake and to form levelled shades. Acid generates cations on fibre and temperature helps to substitute the negative part of the acid with anionic dye molecules.

Sources: en.wikipedia.org

Notes from published material

The most expensive process was to preserve the body by dehydration and protect against pests, such as insects. Almost all of the actions Herodotus described served one of these two functions. First, the brain was removed from the cranium through the nose; the gray matter was discarded. Modern mummy excavations have shown that instead of an iron hook inserted through the nose as Herodotus claims, a rod was used to liquefy the brain via the cranium, which then drained out the nose by gravity. The embalmers then rinsed the skull with certain drugs that mostly cleared any residue of brain tissue and also had the effect of killing bacteria. Next, the embalmers made an incision along the flank with a sharp blade fashioned from an Ethiopian stone and removed the contents of the abdomen. Herodotus does not discuss the separate preservation of these organs and their placement either in special jars or back in the cavity, a process that was part of the most expensive embalming, according to archaeological evidence. The abdominal cavity was then rinsed with palm wine and an infusion of crushed, fragrant herbs and spices; the cavity was then filled with spices including myrrh, cassia, and, Herodotus notes, "every other sort of spice except frankincense", also to preserve the person. The body was further dehydrated by placing it in natron, a naturally occurring salt, for 70 days. Herodotus insists that the body did not stay in the natron longer than 70 days.

Blood pressure ≥140/90 mmHg Dyslipidemia: TG ≥1.695 mmol/L and HDL-C ≤0.9 mmol/L (men), ≤1.0 mmol/L (women) Central obesity: waist:hip ratio >0.90 (men); >0.85 (women), or BMI >30 kg/m2 Microalbuminuria: urinary albumin excretion ≥20 μg/min or albumin:creatinine ≥30 mg/g

Sex differences in hormone levels may induce women to respond differently than men to nicotine. When women undergo cyclic changes or different hormonal transition phases (menopause, pregnancy, adolescence), there are changes in their progesterone levels. Therefore, females have an increased biological vulnerability to nicotine's reinforcing effects compared to males, and progesterone may be used to counter this enhanced vulnerability. This information supports the idea that progesterone can affect behavior. Similar to nicotine, cocaine also increases the release of dopamine in the brain. The neurotransmitter is involved in the reward center and is one of the main neurotransmitters involved with substance abuse and reliance. In a study of cocaine users, it was reported that progesterone reduced craving and the feeling of being stimulated by cocaine. Thus, progesterone was suggested as an agent that decreases cocaine craving by reducing the dopaminergic properties of the drug.

Sources: en.wikipedia.org

Frequently asked questions

Where was Semax developed?

It originated at the Institute of Molecular Genetics in Moscow during the 1980s. The work was carried out by a Russian research group that specialized in peptide neuropharmacology.

Is Semax an approved medication anywhere?

It is registered as a medicine in Russia and has been used clinically there for decades. No regulatory agency in Western Europe or North America has approved it for any indication.

What is the relationship to ACTH?

Semax corresponds to the four-to-ten fragment of adrenocorticotropic hormone. Because it omits the first three residues, it lacks the adrenal-stimulating action of the full hormone.

用什么方法确认分子量?

电喷雾或基质辅助激光解吸电离质谱是常用手段,测得的质子化离子质荷比可换算为分子量。结果与理论值落在合理误差内,才支持结构一致的判断。

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