Everything below concerns ACTH(4–10). We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2025-11-14. Where a claim depends on a specific study, the study is described rather than over-claimed.
Development took place during the 1980s at institutes of the Russian Academy of Sciences, where peptide fragments of ACTH were screened for cognitive and neuroprotective effects. The compound received regulatory approval in Russia as a nasal preparation, marketed for conditions such as ischemic stroke, transient ischemic attacks, and optic nerve disorders. Registration in other countries has not followed. Most published clinical reports originate from a small number of Russian research groups, and independent replication outside that setting remains limited. The regulatory status therefore differs sharply between Russia and the rest of the world.
Laboratory work points toward modulation of neurotrophic signaling, particularly expression of brain-derived neurotrophic factor and nerve growth factor in hippocampal tissue. Studies also describe effects on monoamine turnover, inflammatory mediators, and oxidative markers. These observations come mainly from animal models and cultured cells, so the causal chain in humans is not firmly established. Whether the reported molecular changes translate into measurable clinical benefit is an open question. Reviews generally present the mechanism as plausible rather than demonstrated.
Clinical evidence consists largely of small trials with modest sample sizes, often without independent replication. Reported endpoints include cognitive scores, recovery after stroke, and visual function, but study designs vary widely and few trials meet contemporary reporting standards. Systematic reviewers have noted a high risk of bias in several of these reports. No large multicenter trial conducted outside Russia has been published. The compound is therefore best described as investigational in most jurisdictions, with its clinical role still unresolved.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Sequence | Met-Glu-His-Phe-Pro-Gly-Pro | Heptapeptide; ACTH(4-10) analog extended at C-terminus |
| Molecular mass | ~813.9 Da | Free peptide, unmodified |
| Appearance | White to off-white powder | Typical lyophilized solid |
| Solubility | Soluble in water and saline | Also soluble in common aqueous buffers |
| Storage (solid) | -20 °C, desiccated | Protect from moisture and repeated thawing |
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.
Pharmacological accounts link semax to melanocortin signalling and to modulation of neurotrophic factor expression, particularly brain-derived neurotrophic factor and nerve growth factor. Much of this evidence comes from rodent studies using intranasal delivery, a route chosen because it allows peptides to reach the central nervous system with limited systemic exposure. Whether the same mechanisms operate in humans at comparable magnitude remains an open question. The precise receptor or receptors responsible for the reported behavioural and neuroprotective effects have not been conclusively identified.
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.
Biosynthesis of morphine in the opium poppy begins with two tyrosine derivatives, dopamine and 4-hydroxyphenylacetaldehyde. Condensation of these precursors yields the primary intermediate higenamine (norcoclaurine). Subsequent action of four enzymes yields the tetrahydroisoquinoline reticuline, which is converted into salutaridine, thebaine, and oripavine. The enzymes involved in this process are the salutaridine synthase, salutaridine:NADPH 7-oxidoreductase and the codeinone reductase. Researchers are attempting to reproduce the biosynthetic pathway that produces morphine in genetically engineered yeast. In June 2015 the S-reticuline could be produced from sugar and R-reticuline could be converted to morphine, but the intermediate reaction could not be performed. In August 2015 the first complete synthesis of thebaine and hydrocodone in yeast was reported, but the process would need to be 100,000 times more productive to be suitable for commercial use.
=== Ancient world === Prehistoric medicine incorporated plants (herbalism), animal parts, and minerals. In many cases these materials were used ritually as magical substances by priests, shamans, or medicine men. Well-known spiritual systems include animism (the notion of inanimate objects having spirits), spiritualism (an appeal to gods or communion with ancestor spirits); shamanism (the vesting of an individual with mystic powers); and divination (magically obtaining the truth). The field of medical anthropology examines the ways in which culture and society are organized around or impacted by issues of health, health care and related issues. The earliest known medical texts in the world were found in the ancient Syrian city of Ebla and date back to 2500 BCE. Other early records on medicine have been discovered from ancient Egyptian medicine, Babylonian Medicine, Ayurvedic medicine (in the Indian subcontinent), classical Chinese medicine (Alternative medicine) predecessor to the modern traditional Chinese medicine), and ancient Greek medicine and Roman medicine. In Egypt, Imhotep (3rd millennium BCE) is the first physician in history known by name. The oldest Egyptian medical text is the Kahun Gynaecological Papyrus from around 2000 BCE, which describes gynaecological diseases. The Edwin Smith Papyrus dating back to 1600 BCE is an early work on surgery, while the Ebers Papyrus dating back to 1500 BCE is akin to a textbook on medicine.
== Veterinary use == In the 17th century Robert Boyle investigated opium as a poison by giving opium to a dog. This experiment is the earliest documented use of an opioid in a domestic animal. In 1659, Christopher Wren and Boyle induced stupor in a dog via intravenous administration. Friedrich Wilhelm Adam Sertürner after isolating morphine from opium administered an aqueous alcoholic solution of morphine to four dogs and a mouse — one dog died and the others experienced sedation, convulsion, and emesis. Frederick Hobday was the first to report the varied effects of morphine in different species: in 1908 Hobday reported that morphine causes delirium in cats and horses but for dogs it induced anaesthesia. Hobday proposed that dogs be given 1/16th of a grain per pound to induce analgesia and anaesthesia in dogs. Despite the understanding of morphine's use in dogs it was not considered useful for other animals and in 1917, Howard Jay Milks wrote that morphine did not induce analgesia in animals other than dogs. Milks did report that 2 to 5 grains of morphine induced sedation in horses. Most research afterwards was more concerned with adverse effects of morphine as opposed to analgesic potential and opioids were not frequently used until the 1980s in veterinary practice, when an increased awareness of providing analgesia began to occur. Common routes for administration of opioids in veterinary medicine are intra-articular, intravenous, subcutaneous, intramuscular, intranasal, and transdermal. Common opioids in veterinary medicine are: morphine, fentanyl, and buprenorphine.
In addition to CYP2B6, CYP2A6 may be involved in the metabolism of selegiline to a lesser extent. Birth control pills containing the synthetic estrogen ethinylestradiol and a progestin like gestodene or levonorgestrel have been found to increase peak levels and overall exposure to oral selegiline by 10- to 20-fold. High levels of selegiline can lead to loss of MAO-B selectivity and inhibition of MAO-A as well. This increases susceptibility to side effects and interactions of non-selective monoamine oxidase inhibitors (MAOIs), such as tyramine-induced hypertensive crisis and serotonin toxicity when combined with serotonergic medications. However, this study had a small sample size of four individuals as well as other methodological limitations. The precise mechanism underlying the interaction is unknown, but is likely related to cytochrome P450 inhibition and consequent inhibition of selegiline first-pass metabolism by ethinylestradiol. In contrast to birth control pills containing ethinylestradiol, menopausal hormone therapy with estradiol and levonorgestrel did not modify peak levels of selegiline and only modestly increased overall exposure (+59%). Hence, menopausal hormone therapy does not pose the same risk of interaction as ethinylestradiol-containing birth control pills when taken together with selegiline. Overall exposure to selegiline with oral selegiline has been found to be 23-fold lower in people taking anticonvulsants known to strongly activate drug-metabolizing enzymes. The anticonvulsants included phenobarbital, phenytoin, carbamazepine, and amobarbital.
Sources: en.wikipedia.org
This work hinged on his demonstration that red blood cell glutathione was unstable to oxidative stress. Later, he was to develop an assay for glutathione that was widely used in studies of red cell oxidative metabolism. He was later transferred to Camp Detrick in Frederick, Maryland (1954–1955), where he studied Q fever. He was honorably discharged from the Army with the rank of captain. Beutler then joined the faculty of the Department of Medicine at the University of Chicago, where he studied iron metabolism and red blood cell metabolism. In 1959, he became chairman of the Department of Medicine of the City of Hope National Medical Center in Duarte, California, and in 1979 assumed the chairmanship of the Department of Clinical Research at the Scripps Clinic and Research Foundation. Three years later, he was asked to become Chairman of a merged department (the Department of Molecular and Experimental Medicine) at Scripps, which later became The Scripps Research Institute in La Jolla, CA. He maintained his position as Chairman until his 80th birthday, only a few days before his death. Not long after moving to California, Beutler made one of his most important contributions. A new colleague at the City of Hope and ultimately a lifelong friend, Susumu Ohno had recently demonstrated that the histologically observable Barr body present in the nuclei of mammalian female cells was a hyperchromatic X chromosome. Beutler immediately recognized that this might account for the variable expression of X-linked genes in females heterozygous for X-linked mutations.
The active site can be characterized into two sub-sites denoted as S1’ and S1. The S1’ sub-site is the hydrophobic pocket of the enzyme, and Tyr-248 acts to ‘cap’ the hydrophobic pocket after substrate or inhibitor is bound (SITE). The hydrogen bonding from the hydroxyl group in Tyr-248 facilitates this conformation due to interaction with the terminal carboxylates of substrates that bind. Substantial movement is required for this enzyme and induced fit model explains how this interaction occurs. A triad of residues interact to the C-terminal carboxylate through hydrogen bonding:
=== Column technology === Early gas chromatography used packed columns, made of block 1–5 m long, 1–5 mm diameter, and filled with particles. The resolution of packed columns was improved by the invention of capillary column, in which the stationary phase is coated on the inner wall of the capillary.
A 1986 study published in the American Journal of Public Health claimed that, citing World Bank data, the Soviet model provided a better quality of life and human development than market economies at the same level of economic development in most cases. Some scholars on the left have posited that the end of the Soviet Union and communism as a global force allowed neoliberal capitalism to become a global system, which has resulted in rising economic inequality. In her 2012 book The Communist Horizon, Jodi Dean argued that there is a double standard among all sides of the political spectrum, including conservatives, liberals, and social democrats, in how communism and capitalism are perceived nearly two decades after the dissolution of the Soviet Union. Dean stated that the worst excesses of capitalism are often minimized, while communism is often equated only with the Soviet Union, and experiments in Eastern Europe, Latin America, Africa, and Asia are often ignored, with an emphasis placed on the Stalin era and its violent excesses including gulags, purges, droughts and famines, and almost no consideration for the industrialization and modernization of the Soviet economy, the successes of Soviet science (such as the Soviet space program), or the rise in the standard of living for the once predominantly agrarian society.
In John Gould's Handbook to the Birds of Australia, first published in 1865, he lamented the loss of the emu from Tasmania, where it had become rare and has since become extinct; he noted that emus were no longer common in the vicinity of Sydney and proposed that the species be given protected status. In the 1930s, emu killings in Western Australia peaked at 57,000, and culls were also mounted in Queensland during this period due to rampant crop damage. In the 1960s, bounties were still being paid in Western Australia for killing emus, but since then, wild emus have been granted formal protection under the Environment Protection and Biodiversity Conservation Act 1999. Their occurrence range is between 4,240,000 and 6,730,000 km2 (1,640,000–2,600,000 sq mi), and a 1992 census suggested that their total population was between 630,000 and 725,000. Their population trend is thought to be stable and the International Union for Conservation of Nature assesses their conservation status as being of least concern. The isolated emu population of the New South Wales North Coast Bioregion and Port Stephens is listed as endangered by the New South Wales Government. Although the population of emus on mainland Australia is thought to be higher now than it was before European settlement, some local populations are at risk of extinction. The threats faced by emus include the clearing and fragmentation of areas of suitable habitat, deliberate slaughter, collisions with vehicles and predation of the eggs and young.
Sources: en.wikipedia.org
Semax is a synthetic seven-amino-acid peptide derived from a fragment of corticotropin. It is used in Russia as a nasal preparation, while elsewhere it is studied as a research compound. It is not approved as a medicine in most countries.
Its sequence corresponds to the 4-10 region of corticotropin extended by three residues. This fragment lacks the region responsible for adrenal steroid release, so it is explored for neural rather than hormonal effects. The relationship explains the compound's classification among ACTH-derived peptides.
It holds approval in Russia for several neurological indications as a nasal spray or drop formulation. Regulatory agencies in the United States and the European Union have not approved it. Products sold elsewhere are generally labeled for research use only.
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.