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 2026-02-01. Anything still debated is marked as such rather than presented as settled.
Pharmacokinetic accounts emphasize rapid breakdown. After intravenous dosing the intact peptide disappears from blood within minutes, and nasal delivery produces low but measurable concentrations. Metabolites rather than the parent molecule may account for part of the observed activity, although the relative contribution is unresolved. Dosing in the literature varies widely and no optimal schedule has been agreed. These gaps are regularly cited as a reason the findings have not produced broad clinical adoption beyond the original research setting.
Proposed mechanisms center on neurotrophic signaling rather than on classical melanocortin receptor activation. Rodent experiments have reported shifts in the expression of brain-derived neurotrophic factor and nerve growth factor after administration, together with changes in the associated receptor systems. Several authors argue that the peptide acts largely through its degradation products and their interaction with peptidergic pathways, but this remains a hypothesis rather than a settled finding. No single molecular target has been identified in a way that the field broadly accepts.
Clinical reports describe use in ischaemic stroke, transient ischaemic attack, optic nerve conditions, and cognitive complaints, but most of these studies are small and were conducted in a single region. Systematic reviews have generally described the evidence base as limited in size and variable in methodological quality. Randomised controlled data suitable for international regulatory assessment are scarce. As a result, major treatment guidelines outside Russia do not include the peptide, and interest in it remains largely research-driven rather than routine clinical.
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. It is described in the literature as an analogue of the ACTH(4–10) fragment, a short N-terminal portion of adrenocorticotropic hormone that retains some neurotropic activity without the full hormonal effects of the parent peptide. The molecule carries a methionine residue at the N-terminus and two proline residues near the C-terminus, features that shape both its interactions with receptor systems and its chemical stability. The free peptide corresponds to the formula C37H51N9O10S and a molecular mass near 813.9 Da.
The compound was developed in the 1980s at the Institute of Molecular Genetics in Moscow, where it emerged from research on short ACTH fragments and their effects on the central nervous system. Russian pharmaceutical listings describe it as a nootropic and neuroprotective agent, most often formulated as nasal drops. It is not a marketed medicine in the United States or the European Union, and no pharmacopoeial monograph covers it. Consequently, most published clinical experience with the substance originates from a small number of research centres, mainly in Russia and neighbouring countries.
| Property | Value | Notes |
|---|---|---|
| Primary research models | Rodent studies | Largest share of published data |
| Reported markers | BDNF and NGF expression | Measured mainly in animal tissue |
| Common administration | Intranasal | Matches the registered formulation |
| Blood residence time | Minutes | Rapid enzymatic degradation |
| Evidence quality | Small trials, limited replication | Noted repeatedly in reviews |
纯度评估以反相高效液相色谱为主，通过主峰面积百分比给出粗略结果，再配合电喷雾质谱核对分子量。氨基酸分析可验证组成比例，手性色谱或毛细管电泳用于检查残基构型。常见杂质包括缺失序列的短肽、氧化产物与二聚体。由于多数市售品不附带完整检验报告，独立第三方检测常被用来核实标称值。
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。
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.
Practical handling follows from those properties. Bulk material is best divided into single-use portions soon after receipt, because each thaw exposes the whole container to moisture and temperature cycling. Vials should be allowed to reach room temperature before opening to prevent condensation on the powder. Low-binding plasticware reduces loss of dilute solutions, and sterile filtration is used when a preparation must remain free of microbial growth. Records of batch number, reconstitution date and storage history are what allow a later analytical result to be interpreted meaningfully.
Identity and purity of Semax are established mainly by reversed-phase high-performance liquid chromatography coupled with mass spectrometry. The chromatographic trace gives a purity estimate as a percentage of total peak area, while electrospray or matrix-assisted laser desorption ionization confirms the molecular mass against the calculated value. Amino acid analysis and sequence-specific fragmentation provide further confirmation when a supplier's chain of custody is unclear. Vendors frequently quote a purity figure without stating the detection wavelength or the integration method, which limits how far one number can be compared with another.
Stability depends heavily on physical state. Lyophilized powder held dry, cold and dark retains its content over long periods, whereas dissolved peptide begins to change within days at room temperature. The most cited degradation route is oxidation of the methionine residue, which converts the peptide to a sulfoxide form that elutes differently on chromatography. Hydrolysis of amide bonds and adsorption onto container walls contribute smaller losses. Buffers that exclude oxygen from the headspace slow the oxidation pathway, but no single condition prevents all change indefinitely.
Official website Mind Changers, Series 4: Arden House BBC Radio programme which interviews Langer about one of her experiments. The Young Ones Ellen Langer's Counter Clockwise study was the basis for this BBC documentary series. The Great Lesson The Great Lesson: A New Film About Mind and Body: Featuring Dr. Ellen Langer
== Nomenclature == This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is ribitol:NAD+ 2-oxidoreductase. Other names in common use include adonitol dehydrogenase, ribitol dehydrogenase A (wild type), ribitol dehydrogenase B (mutant enzyme with different properties), and ribitol dehydrogenase D (mutant enzyme with different properties).
According to the gene centered view of evolution, most genes are "selfish" only insofar as to compete with other genes or alleles but usually they fulfill a function for the organisms, whereas "parasitic genetic elements", at least initially, do not make a positive contribution to the fitness of the organism. As of December 2019, the UniProtKB database contains 188 entries manually annotated as inteins, ranging from just tens of amino acid residues to thousands. The first intein was found encoded within the VMA gene of Saccharomyces cerevisiae. They were later found in fungi (ascomycetes, basidiomycetes, zygomycetes and chytrids) and in diverse proteins as well. A protein distantly related to known inteins containing protein, but closely related to metazoan hedgehog proteins, has been described to have the intein sequence from Glomeromycota. Many of the newly described inteins contain homing endonucleases and some of these are apparently active. The abundance of intein in fungi indicates lateral transfer of intein-containing genes. While in eubacteria and archaea, there are 289 and 182 currently known inteins. Not surprisingly, most intein in eubacteria and archaea are found to be inserted into nucleic acid metabolic protein, like fungi. Inteins vary greatly, but many of the same intein-containing proteins are found in a number of species. For example, pre-mRNA processing factor 8 (Prp8) protein, instrumental in the spliceosome, has seven different intein insertion sites across eukaryotic species.
American banker and amateur ethnomycologist R. Gordon Wasson and his wife, Valentina P. Wasson, a physician, studied the ritual use of psychoactive mushrooms by the native population in the Mazatec village Huautla de Jiménez, Mexico. In 1957, Wasson described the psychedelic visions he experienced during these rituals in "Seeking the Magic Mushroom", an article published in the American weekly Life magazine. Later the same year they were accompanied on a follow-up expedition by French mycologist Roger Heim, who identified several of the mushrooms as Psilocybe species. Heim cultivated the mushrooms in France and sent samples for analysis to Albert Hofmann, a chemist employed by the Swiss pharmaceutical company Sandoz. Hofmann—who had synthesized lysergic acid diethylamide (LSD) in 1938—led a research group that isolated and identified the psychoactive alkaloids psilocybin and psilocin from Psilocybe mexicana, publishing their results in 1958. The team was aided in the discovery process by Hofmann's willingness to ingest mushroom extracts to help verify the presence of the active compounds. Next, Hofmann's team synthesized several structural analogs of these compounds to examine how these structural changes affect psychoactivity. This research led to the development of ethocybin and CZ-74. Because these compounds' physiological effects last only about three and a half hours (about half as long as psilocybin's), they proved more manageable for use in psycholytic therapy.
Chemical specificity is the ability of binding site of a macromolecule (such as a protein) to bind specific ligands. The fewer ligands a protein can bind, the greater its specificity. Specificity describes the strength of binding between a given protein and ligand. This relationship can be described by a dissociation constant, which characterizes the balance between bound and unbound states for the protein-ligand system. In the context of a single enzyme and a pair of binding molecules, the two ligands can be compared as stronger or weaker ligands (for the enzyme) on the basis of their dissociation constants. (A lower value corresponds to a stronger binding.) Specificity for a set of ligands is unrelated to the ability of an enzyme to catalyze a given reaction, with the ligand as a substrate. If a given enzyme has a high chemical specificity, this means that the set of ligands to which it binds is limited, such that neither binding events nor catalysis can occur at an appreciable rate with additional molecules. An example of a protein-ligand pair whose binding activity can be highly specific is the antibody-antigen system. Affinity maturation typically leads to highly specific interactions, whereas naive antibodies are promiscuous and bind a larger number of ligands. Conversely, an example of a protein-ligand system that can bind substrates and catalyze multiple reactions effectively is the Cytochrome P450 system, which can be considered a promiscuous enzyme due to its broad specificity for multiple ligands.
Sources: en.wikipedia.org
The xanthophyll cycle involves the enzymatic removal of epoxy groups from xanthophylls (e.g. violaxanthin, antheraxanthin, diadinoxanthin) to create so-called de-epoxidised xanthophylls (e.g. diatoxanthin, zeaxanthin). These enzymatic cycles were found to play a key role in stimulating energy dissipation within light-harvesting antenna proteins by non-photochemical quenching- a mechanism to reduce the amount of energy that reaches the photosynthetic reaction centers. Non-photochemical quenching is one of the main ways of protecting against photoinhibition. In higher plants, there are three carotenoid pigments that are active in the xanthophyll cycle: violaxanthin, antheraxanthin, and zeaxanthin. During light stress, violaxanthin is converted, i.e. reduced, to zeaxanthin via the intermediate antheraxanthin, which plays a direct photoprotective role acting as a lipid-protective anti-oxidant and by stimulating non-photochemical quenching within light-harvesting proteins. This conversion of violaxanthin to zeaxanthin is done by the enzyme violaxanthin de-epoxidase (EC 1.23.5.1), while the reverse reaction, i.e. oxidation, is performed by zeaxanthin epoxidase (EC 1.14.15.21). In diatoms and dinoflagellates, the xanthophyll cycle consists of the pigment diadinoxanthin, which is transformed into diatoxanthin (diatoms) or dinoxanthin (dinoflagellates) under high-light conditions. Wright et al.
The brain is particularly vulnerable to chemicals that are able to cross the blood-brain barrier. Body-first and brain-first models of Parkinson's disease propose that there are two distinct avenues through which environmental toxicants can enter the nervous system: (1) ingested into the gut and affecting the enteric nervous system (body-first), or (2) inhaled through the nose and affecting the olfactory bulb (brain-first). The World Health Organization (WHO) recommends reducing exposure to environmental factors associated with PD, including pesticides, trichloroethylene (TCE), and air pollution. Traumatic brain injury and Type 2 diabetes are additional risk factors. Exercise, coffee consumption, and diets rich in fruits, vegetables, whole grains, and fish are protective factors associated with lower risk of PD.
Cocaine is a highly-trafficked prohibited drug. The value of the global market for illicit cocaine was estimated at between $94 and $143 billion in 2017. In 2022, illicit sales in Europe were estimated at $11.1 billion. In 2020, almost 2,000 tons of cocaine were produced for distribution through illicit markets.
=== General references === Ambrose, W.; Novak, S.W.; Abdelrehim, I. (2004). "Powdered obsidian for determining hydration rates and site thermometry". Mediterranean Archaeology and Archaeometry. 4 (2): 17–31. Liritzis (2006). "SIMS-SS A new obsidian hydration dating method: analysis and theoretical principles". Archaeometry. 48 (3): 533–547. Bibcode:2006Archa..48..533L. doi:10.1111/j.1475-4754.2006.00271.x. Rogers, A. K. (2008). "Field data validation of an algorithm for computing obsidian effective hydration temperature". Journal of Archaeological Science. 35 (2): 441–447. Bibcode:2008JArSc..35..441R. doi:10.1016/j.jas.2007.04.009. Eerkens, J.W; Vaughn, K.J; Carpenter, T.R; Conlee, C.A; Linares Grados, Moises; Schreiber, K (2008). "Obsidian hydration dating on the South Coast of Peru". Journal of Archaeological Science. 35 (8): 2231–2239. Bibcode:2008JArSc..35.2231E. doi:10.1016/j.jas.2008.02.009. Liritzis, I; Laskaris, N (2009). "Advances in obsidian hydration dating by secondary ion mass spectrometry: World examples". Nuclear Instruments and Methods in Physics Research Section B. 267 (1): 144–150. Bibcode:2009NIMPB.267..144L. doi:10.1016/j.nimb.2008.10.092.
== Career == Stobart was born in Cumberland in England in November 1961, the fourth child of Eddie and Nora Stobart. He worked for the family business from his teenage years, joining the management of Eddie Stobart Ltd in 1986. Stobart was Chief Operating Officer of the Stobart Group from 2007 to 2014 and chief executive officer of Eddie Stobart Logistics from 2014 to 2017. He then served as Executive Chairman of GreenWhiteStar Acquisitions from 2019 to 2021 and became Deputy Group CEO of Culina Group in 2021.
Sources: en.wikipedia.org
The main proposal is modulation of neurotrophic factors such as brain-derived neurotrophic factor, supported largely by animal experiments. Receptor-level targets have not been firmly established. Most reviews describe the mechanism as only partially characterized.
The compound is registered as a medicine in Russia, so clinical work has concentrated there. Trials elsewhere are few and generally small. This geographic concentration is a recognized limitation in evidence reviews.
Some fraction may reach the central nervous system through olfactory pathways, and this is often cited as the rationale for the nasal route. The size of that fraction in humans is not well quantified. Blood concentrations after nasal dosing are low, which complicates measurement.
It is described as a synthetic analogue of the ACTH(4–10) fragment, a short segment of adrenocorticotropic hormone. Its sequence differs from that fragment and includes two proline residues, which influence stability and behaviour in solution.