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 2026-03-21 and is reviewed periodically as new material appears.
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.
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.
Routine characterization relies on reversed-phase high-performance liquid chromatography to establish purity and on mass spectrometry to confirm molecular identity. Electrospray ionization and matrix-assisted laser desorption ionization are both used for mass verification. Amino acid analysis and peptide mapping can detect sequence errors. Common impurities include truncated sequences, methionine sulfoxide formed by oxidation, and deamidated products. Chromatograms are usually recorded near 214 nm, where the peptide backbone absorbs, and purity is reported as the percentage area of the principal peak.
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.
Published research has focused mainly on neurological and cognitive endpoints in animal models, with proposed mechanisms involving brain-derived neurotrophic factor and related signalling pathways. A substantial share of the human data originates from a limited number of research groups, and independent replication in other countries remains sparse. Regulatory status reflects that distribution: the peptide is registered as a medicine in Russia and appears in some neighbouring markets, while elsewhere it is handled as a research chemical without approved therapeutic labelling. Questions about dose-response relationships, long-term effects, and comparability across studies are still open.
Lyophilised powder is normally kept at -20 °C in a desiccated container, with some suppliers recommending -80 °C for long-term archival storage. Repeated freeze-thaw cycles are the most common cause of avoidable loss, so aliquoting before freezing reduces variability between working sessions. Dissolved peptide is far less stable than the dry solid and is usually prepared fresh or held briefly at 4 °C. Aqueous solutions support both hydrolysis of the backbone and oxidation of the N-terminal methionine, and these two routes dominate degradation under ordinary laboratory conditions.
Identity and purity are confirmed with reversed-phase high-performance liquid chromatography, typically monitored at 214 nanometres where the peptide bond absorbs. Mass spectrometry, either electrospray or MALDI-TOF, verifies molecular mass against the theoretical value and detects truncation or adduct formation. Amino acid analysis and peptide mapping provide additional confirmation when required. The most frequently reported impurities are deletion sequences from incomplete coupling, methionine sulfoxide from oxidation, and dimeric species formed through non-covalent aggregation. Impurity profiles depend strongly on the synthesis and purification route chosen by the producer.
In a recent but highly controversial interpretation, it has also been speculated that olfactory receptors might really sense various vibrational energy-levels of a molecule rather than structural motifs via quantum coherence mechanisms. As evidence it has been shown that flies can differentiate between two odorant molecules which only differ in hydrogen isotope (which will drastically change vibrational energy levels of the molecule). Not only could the flies distinguish between the deuterated and non-deuterated forms of an odorant, they could generalise the property of "deuteratedness" to other novel molecules. In addition, they generalised the learned avoidance behaviour to molecules which were not deuterated but did share a significant vibration stretch with the deuterated molecules, a fact which the differential physics of deuteration (below) has difficulty in accounting for. Deuteration changes the heats of adsorption and the boiling and freezing points of molecules (boiling points: 100.0 °C for H2O vs. 101.42 °C for D2O; melting points: 0.0 °C for H2O, 3.82 °C for D2O), pKa (i.e., dissociation constant: 9.71 × 10−15 for H2O vs. 1.95 × 10−15 for D2O, cf. heavy water) and the strength of hydrogen bonding. Such isotope effects are exceedingly common, and so it is well known that deuterium substitution will indeed change the binding constants of molecules to protein receptors. It has been claimed that human olfactory receptors are capable of distinguishing between deuterated and undeuterated isotopomers of cyclopentadecanone by vibrational energy level sensing.
X-ray diffraction studies of microcrystals revealed atomistic details of core region of amyloid, although only for simplified peptides having a length remarkably shorter than that of peptides or proteins involved in disease. The crystallographic structures show that short stretches from amyloid-prone regions of amyloidogenic proteins run perpendicular to the filament axis, consistent with the "cross-β" feature of amyloid structure. They also reveal a number of characteristics of amyloid structures – neighboring β-sheets are tightly packed together via an interface devoid of water (therefore referred to as dry interface), with the opposing β-strands slightly offset from each other such that their side-chains interdigitate. This compact dehydrated interface created was termed a steric-zipper interface. There are eight theoretical classes of steric-zipper interfaces, dictated by the directionality of the β-sheets (parallel and anti-parallel) and symmetry between adjacent β-sheets. A limitation of X-ray crystallography for solving amyloid structure is represented by the need to form microcrystals, which can be achieved only with peptides shorter than those associated with disease. Although bona fide amyloid structures always are based on intermolecular β-sheets, different types of "higher order" tertiary folds have been observed or proposed. The β-sheets may form a β-sandwich, or a β-solenoid which may be either β-helix or β-roll. Native-like amyloid fibrils in which native β-sheet containing proteins maintain their native-like structure in the fibrils have also been proposed.
==== Sovereignty ==== During his tenure as prime minister, Mahathir asserted Malaysia's sovereignty over several features in the Spratly Islands, claiming Swallow Reef in 1983, Ardasier Reef and Mariveles Reef in 1986, and Investigator Shoal and Erica Reef in 1999. His administration cited Malaysia's continental shelf limits and the 1982 UNCLOS as the basis for these claims, while also responding to Vietnam's territorial activities in the region. To strengthen Malaysia's position, Mahathir oversaw the transformation of Swallow Reef into an artificial island with military fortifications, establishing it as a permanent naval outpost. Despite this militarisation, he maintained diplomatic engagement with Beijing, balancing relations with ASEAN claimants and employing a hedging strategy involving China and the United States. Mahathir's foreign policy towards China on the Spratlys was notably pragmatic. While Malaysia pursued its territorial claims, he emphasised dialogue over confrontation. In 1993, he stated that Malaysia had "no problem with China" regarding the Spratlys, and in 1994, he welcomed China's proposal for joint exploration, opposing further internationalisation of the dispute.
== Description == Leaves are aromatic, simple and lanceolate, obovate-elliptic or elliptic, size of 5–15 cm × 2–5 cm, coriaceous to thickly coriaceous. The leaves are 5–15 cm × 1.5–5 cm, apex acute, lower side pubescent. Flowers are solitary, bisexual, pink to dark red, axillary or subterminal. The perianth has 7–12 lobes, arranged spirally; 11–20 stamens, arranged spirally, with short, thick filaments; and usually 8 carpels, free, arranged in a single whorl. Flower peduncle size is 1.5–4 cm, tepals number range from seven to twelve, and are broadly elliptic to broadly ovate, anthers size is 1–1.5 mm, pollen grains trisyncolpate. The fruit is a capsule-like follicetum, star-shaped, reddish-brown, consisting of six to eight follicles arranged in a whorl. Each follicle is boat-shaped, 1–2 cm long, rough and rigid, color reddish-brown, with 1 seed, opening along the ventral edge when ripe. carpels size of 10 mm long, boat-shaped; they are hard and wrinkled, containing one seed. Seeds are brown, compressed ovoid, smooth, shiny and brittle with approximate size of 8–9 mm × 6 mm. Differences with similar taxa: Illicium anisatum had smaller fruits that does not form a regular star due to the abortion of some carpels. Also fruit follicles are not swollen in the middle and had a more pointed apex. Also usually had more than 8 follicles and the fruit has weaker odour. The seeds in Illicium anisatum are flat or almost spherical.
== Drug interactions == A significant interaction has also been recorded with allopurinol, and administration of these drugs together should be avoided. Reduction in indinavir and delavirdine plasma levels have been shown to occur when administered simultaneously with didanosine; these drugs should be administered at different times. Ketoconazole, itraconazole, ciprofloxacin should be administered at a different time from didanosine due to interactions with the buffering agent. Administration with drugs with overlapping toxicity, such as zalcitabine and stavudine, is not recommended. Alcohol can exacerbate didanosine's toxicity, and avoiding drinking alcohol while taking didanosine is recommended.
Sources: en.wikipedia.org
Korvezee was the youngest of two daughters of the pastor Willem Korvezee (1858–1913) and his wife Baukje Andringa (1874–1952). Her older sister, Elisabeth “Bets” Korvezee, later became the first female national archivist in the Netherlands. After their father's death in 1913, the family lived in The Hague, where both sisters attended the third municipal HBS, known as the “HBS-voor-jongens” (boys’ HBS), and Antonia showed particular talent for mathematics. She went on to study chemical technology at the Delft Institute of Technology, graduating cum laude in 1922. She then worked as an assistant, first in the department of analytical chemistry and from 1924 to 1938 in the laboratory of Scheffer. Under Frans Everhardus Cornelis Scheffer, she completed her doctorate cum laude in 1930 with a thesis titled “Copper chlorides as a catalyst for the Deacon process.” Between 1930 and 1932, she spent two six-month periods in Paris conducting research on radioactivity in Marie Curie’s laboratory. In 1935, her temporary appointment at Delft was made permanent, and she was appointed lecturer in radioactive decay. Korvezee was passed over for a professorship three times, first nominated in 1936 for the chair of analytical chemistry, and again in 1940 for the chair of physical chemistry despite ranking third in the nomination process.
== External links == The LIVEChart of Nuclides – IAEA AlphaDelta: Stable Isotope fractionation calculator Archived 2011-04-02 at the Wayback Machine National Isotope Development Center Reference information on isotopes, and coordination and management of isotope production, availability, and distribution Isotope Development & Production for Research and Applications (IDPRA) U.S. Department of Energy program for isotope production and production research and development Isosciences Archived 2021-01-18 at the Wayback Machine Use and development of stable isotope labels in synthetic and biological molecules
Lithium-ion Battery at the Encyclopædia Britannica. Degradation Mechanisms and Lifetime Prediction for Lithium-Ion Batteries, NREL, July 2015. Impact of Temperature Extremes on Large Format Li-ion Batteries for Vehicle Applications, NREL, March 2013.
The heightened vigilance of the German garrison as the war entered its final phase made these operations especially hazardous, particularly as they were often attempted at extremely close quarters. On several occasions Rhodesian patrols only narrowly escaped discovery. During one action, two Rhodesian patrols catered for the possibility that Germans might be listening to their transmissions by communicating in Shona, an African language. The LRDG's last actions of the war, in April and May 1945, were to help Tito's partisans capture German-held islands off Dalmatia.
=== Tanks === Centurion – main British early Cold War tank. Conqueror – used from mid 50s to mid 60s to give long range anti-tank support to Centurions. Built to counter IS-3. Chieftain – main British tank of Cold War and mid Cold War. Challenger 1 – Main British tank late Cold War or 1980s.
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.