ACTH(4-10) raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
This page was last updated on 2025-10-21 and is reviewed periodically as new material appears.
Published research covers ischemic stroke, traumatic brain injury, cognitive impairment, optic nerve conditions and attention-related measures. Much of the human evidence comes from small trials conducted in one country, which limits how far the results generalize. Animal models supply the larger share of the data, and effects seen in rodents do not transfer automatically to people. Reviews have noted that methodological reporting is often incomplete, making it difficult to pool results or compare treatment schedules across studies.
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.
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.
Development is attributed to researchers at the Institute of Molecular Genetics in Moscow during the early 1980s, building on earlier Soviet work with ACTH fragments. Russian regulatory approval followed for intranasal use, and the compound has remained commercially available there for decades. Most published human data originate from Russian and, later, some Eastern European clinical reports, which are not always accessible in English translation. Outside that region the material is generally handled as a research chemical rather than a licensed medicine.
| 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 |
Verification of a supplied batch generally combines a certificate of analysis with independent testing, because certificates are self-reported documents. A typical package includes a chromatographic trace, a mass spectrum, and a stated water or counter-ion content. Batch-to-batch consistency matters more than a single purity figure when results are compared across experiments. No single mandatory standard governs research-grade peptide release, so laboratories are expected to define their own acceptance criteria. Residual trifluoroacetate from purification is a frequently overlooked counter-ion.
Lyophilized material is chemically stable for extended periods when kept dry, cold, and protected from light. The powder is hygroscopic, so vials should be warmed to room temperature before opening to reduce condensation on the contents. Once dissolved, the peptide is far less stable because peptide bonds are susceptible to hydrolysis and the methionine residue can oxidize. Solutions are typically aliquoted and held at 2-8 °C for short intervals or frozen for longer ones, and repeated freeze-thaw cycles should be avoided.
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.
Semax is a synthetic heptapeptide whose sequence is Met-Glu-His-Phe-Pro-Gly-Pro. It was developed as a fragment analog of adrenocorticotropic hormone, modeled specifically on the ACTH(4-10) region. The first four residues reproduce that fragment, while a Pro-Gly-Pro tripeptide is appended at the C-terminus. Work on the compound originated in Russia, where it entered clinical use as an intranasal preparation. Its sequence places it among short regulatory peptides studied for effects on the central nervous system rather than on the adrenal axis.
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.
The four substrates of this enzyme are 7-methylxanthine, reduced nicotinamide adenine dinucleotide (NADH), oxygen, and a proton. Its products are xanthine, oxidised NAD+, water, and formaldehyde. The enzyme is a non-heme iron protein that is part of the pathway of caffeine degradation in Pseudomonas putida.
APPI has also been effectively applied for ambient ionization applications lending itself to several practical configurations. One configuration termed desorption APPI (DAPPI) was developed by Haapala et al. and is pictured in the figure here. This device has been applied to the analysis of drugs of abuse in various solid phases, drug metabolites and steroids in urine, pesticides in plant material, etc. APPI has also been interfaced to a DART (direct analysis in real time) source and shown for non-polar compounds such as steroids and pesticides to enhance signal by up to an order of magnitude for N2 flow, which is preferred for DART because it is significantly cheaper and easier to generate then the higher performing use of He. Commercial APPI sources have also been adapted to accept an insertable sampling probe that can deliver or liquid or solid sample to the nebulizer for vaporization and ionization. This configuration is similar to atmospheric solid analysis probe (ASAP) that is based on the use of APCI and therefore is referred to as APPI-ASAP. The benefits of APPI-ASAP vs. APCI-ASAP are similar to those observed in LC/MS, namely higher sensitivity to lower polarity compounds and less background signal for samples in complex matrices. Though ambient ionization has experienced a renaissance in the last decades, it has been used in the security industry for many decades, for example in swab detections at airports.
=== Announcement and delay === Valve announced Half-Life 2 at E3 2003, with demonstrations of the characters, animation and physics. The reaction was positive, and the game won the E3 Game of the Show award. Newell also announced a release date of September 30, 2003, hoping this would motivate the team. They worked long hours to meet the deadline, but by July it was clear they would miss it. Rumors spread of a delay. On September 23, Valve released a statement targeting a release for the holiday season, leading to fan backlash. Newell had been hesitant to announce a delay without a new release date. He said later: "We were paralyzed. We knew we weren't going to make the date we promised, and that was going to be a huge fiasco and really embarrassing. But we didn't have a new date to give people either." The graphics card manufacturer ATI had arranged a promotional event on Alcatraz Island to coincide with the planned release of Half-Life 2. Unable to pull out of the event, Newell gave a prepared speech, demonstrated the Source engine, and left without addressing questions.
Actinides seem to be a little less hard than lanthanides, probably due to a longer spatial extent of 5f atomic orbitals with respect to 4f ones, then a selective separation is possible thanks to ligands bearing soft donors such as nitrogen and sulfur atoms, by a different bonding nature compared to hard donors. Despite the potential separation of actinides, a direct extraction from the PUREX raffinate is very hard, due to the presence of many other interfering species in the feed such as activation and fission products. In this perspective, advanced separation processes involving very selective extracting agents are required to achieve an efficient partitioning for the following transmutation process. To sum up, knowledge of hydration, acid-base interactions, kinetics and thermodynamic stabilities and speciation of actinide and lanthanide ions with ligands is of great value to understand a solvent extraction process and to design new and promising extracting agents.
==== Bill 23, More Homes Built Faster Act, 2022 ==== Minister Clark introduced Bill 23, the More Homes Built Faster Act, 2022, an omnibus bill intended to increase Ontario's housing supply that was described as "one of Premier Ford's largest pieces of legislation" to date. Bill 23 would make sweeping changes affecting nine laws and "every aspect of planning and development" in the province. By November 25, Ford announced a rollback of some of Bill 23's most controversial changes to existing statutes that would have undermined environmental concerns.
Sources: en.wikipedia.org
=== Bacteria === Necrotizing fasciitis is classified into four groups based on the type of bacteria causing the infection. This classification system was first described by Giuliano and his colleagues in 1977. Type I infection: This is the most common type of infection, and accounts for 70–80% of cases. It is caused by a mixture of bacterial types, usually in the abdominal or groin areas. These bacterial species include:
Most important of all, the Butantan Institute became a fertile school for breeding a new generation of Brazilian biochemists, physiologists and pathologists, such as José Moura Gonçalves, Carlos Ribeiro Diniz, Gastão Rosenfeld, Wilson Teixeira Beraldo and Maurício Rocha e Silva, who went on to found a growing number of schools, departments and research laboratories in São Paulo, Rio de Janeiro and Minas Gerais, giving a great impetus to the development of medical and biological research and teaching in Brazil in the second half of the 20th century.
Rearing a relatively small number of grazing animals can be beneficial, as the Food Climate Research Network at Surrey University reports: "A little bit of livestock production is probably a good thing for the environment". In May 2009, Ghent, Belgium, was reported to be "the first [city] in the world to go vegetarian at least once a week" for environmental reasons, when local authorities decided to implement a "weekly meatless day". Civil servants would eat vegetarian meals one day per week, in recognition of the United Nations' report. Posters were put up by local authorities to encourage the population to take part on vegetarian days, and "veggie street maps" were printed to highlight vegetarian restaurants. In September 2009, schools in Ghent are due to have a weekly veggiedag ("vegetarian day") too. Public opinion and acceptance of meat-free food is expected to be more successful if its descriptive words focus less on the health aspects and more on the flavor.
Whose power is to be balanced? Today, no nation or group challenges American power … In fact, should the balance of power operate in its classical form, it would trigger countermoves by states seeking to pose a counterweight to America's expressed ambitions. According to Leffler's exegesis, Bush has invoked a balance of power vocabulary in purpose to integrate the tradition with the hegemonic dilemma. British Orwell Prize-winning policy analyst, Anatol Lieven, comments: In this conception, however, a phrase "was a form of Orwellian doublespeak. The clear intention actually was to be so strong that other countries had no choice but to rally to the side of the United States, concentrating all real power and freedom of action in the hands of America." The surprising rehabilitation of the balance-of-power term in the 2002 NSS "can be accounted for in terms of mythopoetic function that the terminology serves in the document." It keeps alive the traditional concept in a new unipolar world.
=== Pharmacokinetics === Mephedrone is rapidly absorbed and eliminated in humans. After oral or intranasal administration, peak plasma concentrations are typically reached within 0.5 to 1 hour. The drug crosses the blood-brain barrier easily, with a brain-to-plasma ratio of approximately 1.85 in rats. It has a relatively short half-life of approximately 2 hours in plasma and whole blood. The drug and its metabolites can be detected in whole blood and plasma for up to 6 hours post-administration, with some metabolites persisting longer. Mephedrone exhibits enantioselective pharmacokinetics. The R-(+) enantiomer shows higher peak concentrations and a longer half-life compared to the S-(-) enantiomer. The absolute bioavailability of mephedrone is relatively low, at about 10% in rats, suggesting a significant first-pass effect. The percentage of mephedrone bound to plasma proteins is approximately 22%. These pharmacokinetic properties contribute to mephedrone's rapid onset of action, short duration of effects, and the tendency for users to engage in repeated dosing to maintain the desired effects.
Sources: en.wikipedia.org
5-HTP has been used medically and as a supplement under the name oxitriptan in the treatment of depression and for certain other indications. As of 2025, there are no current FDA approved medications containing 5-HTP. It can be potentiated in combination with a peripherally selective aromatic L-amino acid decarboxylase (AAAD) inhibitor such as carbidopa or benserazide. These agents increase the strength and duration of oxitriptan. An investigational combination formulation is oxitriptan/carbidopa.
==== Pleistocene/Holocene boundary in Two Creeks Fossil Forest ==== The Pleistocene is a geological epoch that began about 2.6 million years ago. The Holocene, the current geological epoch, begins about 11,700 years ago when the Pleistocene ends. Establishing the date of this boundary − which is defined by sharp climatic warming − as accurately as possible has been a goal of geologists for much of the 20th century. At Two Creeks, in Wisconsin, a fossil forest was discovered (Two Creeks Buried Forest State Natural Area), and subsequent research determined that the destruction of the forest was caused by the Valders ice readvance, the last southward movement of ice before the end of the Pleistocene in that area. Before the advent of radiocarbon dating, the fossilized trees had been dated by correlating sequences of annually deposited layers of sediment at Two Creeks with sequences in Scandinavia. This led to estimates that the trees were between 24,000 and 19,000 years old, and hence this was taken to be the date of the last advance of the Wisconsin glaciation before its final retreat marked the end of the Pleistocene in North America. In 1952 Libby published radiocarbon dates for several samples from the Two Creeks site and two similar sites nearby; the dates were averaged to 11,404 BP with a standard error of 350 years. This result was uncalibrated, as the need for calibration of radiocarbon ages was not yet understood. Further results over the next decade supported an average date of 11,350 BP, with the results thought to be the most accurate averaging 11,600 BP.
in adults inadequately controlled on their maximally tolerated dose of metformin alone; in adults inadequately controlled with metformin in combination with other glucose-lowering medicinal products, including insulin; in adults already being treated with the combination of empagliflozin and metformin as separate tablets. In the United States it is also indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. In June 2023, the US Food and Drug Administration (FDA) expanded the indication, as an addition to diet and exercise, to improve blood sugar control in children 10 years and older with type 2 diabetes.
=== Cell extract–based === Nobel Prize winner Eduard Buchner was arguably the first to present a cell-free system using yeast extracts, but since then alternative sources have been found. E. coli, wheat germ, and rabbit reticulocytes have all proven useful to create cell-free systems by extraction of their interior components. E. coli 30S extracts have been acquired, for example, by grinding the bacteria with alumina, followed by further cleaning. Similarly, wheat germ has been ground with acid-washed sand or powdered glass to open the cell membranes up. Rabbit reticulocytes have been lysed in a solution of MgCl2 and had the extract filtered away from the membranes by centrifugation.
In tropical grasses, including maize, sorghum, sugarcane, Bermuda grass and in the dicot amaranthus, leaf photosynthetic rates were around 38−40 μmol CO2·m−2·s−1, and the leaves have two types of green cells, i.e. outer layer of mesophyll cells surrounding a tightly packed cholorophyllous vascular bundle sheath cells. This type of anatomy was termed Kranz anatomy in the 19th century by the botanist Gottlieb Haberlandt while studying leaf anatomy of sugarcane. Plant species with the greatest photosynthetic rates and Kranz anatomy showed no apparent photorespiration, very low CO2 compensation point, high optimum temperature, high stomatal resistances and lower mesophyll resistances for gas diffusion and rates never saturated at full sun light. The research at Arizona was designated a Citation Classic in 1986. These species were later termed C4 plants as the first stable compound of CO2 fixation in light has four carbons as malate and aspartate. Other species that lack Kranz anatomy were termed C3 type such as cotton and sunflower, as the first stable carbon compound is the three-carbon PGA. At 1000 ppm CO2 in measuring air, both the C3 and C4 plants had similar leaf photosynthetic rates around 60 μmol CO2·m−2·s−1 indicating the suppression of photorespiration in C3 plants.
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 a short synthetic peptide built from seven amino acids: methionine, glutamic acid, histidine, phenylalanine and three prolines. The sequence derives from the 4-10 fragment of adrenocorticotropic hormone with an added proline-glycine-proline tail. No plant or animal extract is involved; the material is produced by solid-phase peptide synthesis.