If you have been reading about neurotrophic signaling and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-05-22. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
Scientific literature on semax is unevenly distributed. A substantial share of published work originates from a small number of laboratories in Russia, while independent replication elsewhere is limited. Human data consist mostly of small trials with short follow-up, and several reported outcomes rely on subjective rating scales. Questions about how much intact peptide reaches the central nervous system after nasal administration, and how long it persists there, are still unresolved. The compound is best described as an active research subject rather than a settled pharmacological agent.
Solid semax is typically supplied as a lyophilised powder that is hygroscopic and sensitive to moisture, light, and repeated temperature cycling. Long-term storage of the dry peptide is generally recommended at approximately -20 degrees Celsius, while shorter working periods may use refrigeration at 2 to 8 degrees Celsius. Vials should remain tightly closed and desiccated when brought to room temperature, because condensation can damage the material before it is weighed. Dividing a batch into aliquots is preferable to thawing one container repeatedly.
Dissolution is normally performed in water, phosphate-buffered saline, or normal saline, since the peptide is freely soluble in aqueous media and is rarely handled with strong organic solvents. Solution pH should be kept near neutral, because extreme acidity or alkalinity accelerates backbone hydrolysis and encourages oxidation of the methionine side chain. Once dissolved, the material is less stable than the dry powder and is commonly divided into single-use portions and frozen. Buffers containing primary amines, such as Tris, are often avoided because of possible side reactions.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C37H51N9O10S | Calculated for the free peptide |
| Molar mass | 813.9 g/mol | Anhydrous free base |
| Peptide class | Synthetic heptapeptide | ACTH(4-10) analogue |
| Parent fragment | ACTH(4-10) | Adrenocorticotropic hormone segment |
| Developmental origin | Institute of Molecular Genetics, Moscow | Work began in the 1980s |
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.
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.
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.
== Biomarkers of disease == It is important to acknowledge the biomarkers of third-hand smoke because they theoretically indicate the severity and presence of disease. In a recent study involving mice, THS biomarkers were discovered after four weeks of initial exposure at equivalent levels to those found in the homes of people who smoke. Researchers used a system that mimicked exposure to humans and sought out biomarkers found in serum, liver, and brain tissues in the mice. The mice were then exposed to THS at varying months and as early as one month, they began to show signs of increased circulating inflammatory cytokines, tumor necrosis factor, granulocyte macrophage colony stimulating factor, and an increase in the stress hormone epinephrine. Damage from THS exposure continued after two, four, and six months. Such damages included oxidative stress and molecular damage. In a small controlled study of healthy nonsmoking adults, acute dermal exposure to third-hand smoke increased urinary biomarkers of oxidative damage to DNA, lipids and proteins and altered the plasma proteome in a pattern similar to that observed in cigarette smokers, including activation of pathways associated with inflammatory skin disease. Some of the mice also became hyperglycemic and hyperinsulinimic, which could mean that insulin resistance could be a consequence of long-term exposure. This study implies that increased exposure time to THS can have dramatic effects.
== Deaths == 28 March – Paul O'Grady, comedian, actor and drag queen (born 1955) 22 April – Len Goodman, ballroom dancer and television personality (born 1944) 26 November – Terry Venables, football player and manager (born 1943)
=== 1870s === 1869/1870: American beekeeper Ellen Smith Tupper became the first female editor of an entomological journal. 1870: Katharine Murray Lyell was a British botanist, author of an early book on the worldwide distribution of ferns, and editor of volumes of the correspondence of several of the era's notable scientists. 1870: American engineer and chemist Ellen Swallow Richards became the first American woman to earn a degree in chemistry. 1870: Russian chemist Anna Volkova became the first female member of the Russian Chemical Society. 1874: Russian chemist Julia Lermontova became the first Russian woman to receive a PhD in chemistry. 1875: Hungarian archaeologist Zsófia Torma excavated the site of Turdaș-Luncă in Hunedoara County, today in Romania. The site, which uncovered valuable prehistoric artifacts, became one of the most important archaeological discoveries in Europe. 1876–1878: American naturalist Mary Treat studied insectivorous plants in Florida. Her contributions to the scientific understanding of how these plants caught and digested prey were acknowledged by Charles Darwin and Asa Gray. 1878: English entomologist Eleanor Anne Ormerod became the first female Fellow of the Royal Meteorological Society. A few years afterwards, she was appointed as Consulting Entomologist to the Royal Agricultural Society.
=== Da–Di === Jeff Dahn (born 1957), Canadian materials chemist noted for significant contributions to lithium-ion batteries John Dalton (1766–1844), British chemist, physicist and meteorologist, whose work laid the foundations of modern atomic theory and stoichiometric chemistry Marie Maynard Daly (1921–2003), American biochemist who studied the chemistry of histones, protein synthesis, the relationships between cholesterol and hypertension, and uptake of creatine by muscle cells Carl Peter Henrik Dam (1895–1976), Danish biochemist, winner of the 1943 Nobel Prize in Physiology or Medicine for discovering vitamin K and its role in human physiology Samuel J. Danishefsky (born 1936), American organic chemist, natural product total synthesis, 1995/6 Wolf Prize in Chemistry Raymond Davis, Jr.
== Early life and career == Cantelmo was a high school valedictorian. He graduated from Yale University with a degree in molecular biophysics and biochemistry. He worked for about 35 years in the pharmaceutical industry, specializing in high-performance liquid chromatography (HPLC). According to his own accounts and those of family members, he ran three HPLC companies. The last of these was GL Sciences. He left that position prior to the events of 2019. GL Sciences has stated it has no association with Cantelmoism or the use of illegal drugs. Cantelmo had a history of mental health difficulties and prior suicide attempts. He had also used other substances, including mescaline, LSD, and methamphetamine, at earlier points in his life.
Sources: en.wikipedia.org
Codtrace. Archived 1 February 2016 at the Wayback Machine. fishbase.org – Scientific Names for Gadus Fisheries Heritage website, Newfoundland and Labrador (archived) Long term trends in Norwegian cod fisheries – the pioneers Species factsheet on cod from the UK Sea Fish Industry Authority (PDF, 2MB) "Cod" . New International Encyclopedia. 1905.
== Further reading == Perkins, D. H. (1984-12-01). "Proton Decay Experiments". Annual Review of Nuclear and Particle Science. 34 (1): 1–50. Bibcode:1984ARNPS..34....1P. doi:10.1146/annurev.ns.34.120184.000245. ISSN 0163-8998. Luciano Maiani (8 February 2006). The problem of proton decay (PDF). Third NO-VE International Workshop on Neutrino Oscillations in Venice. Venice. Nath, Pran; Fileviez Pérez, Pavel (April 2007). "Proton stability in grand unified theories, in strings and in branes". Physics Reports. 441 (5–6): 191–317. arXiv:hep-ph/0601023. Bibcode:2007PhR...441..191N. doi:10.1016/j.physrep.2007.02.010. S2CID 119542637. Dev, P. S. B.; et al. (2022-09-26), "Searches for Baryon Number Violation in Neutrino Experiments: A White Paper", Journal of Physics G: Nuclear Physics, 51 (3): 033001, arXiv:2203.08771, Bibcode:2024JPhG...51c3001D, doi:10.1088/1361-6471/ad1658
=== Gender dysphoria === Many international guidelines and institutions require persistent, well-documented gender dysphoria as a pre-requisite to starting gender-affirmation therapy. Gender dysphoria refers to the psychological discomfort or distress that an individual can experience if their sex assigned at birth is incongruent with that person's gender identity. Signs of gender dysphoria can include comorbid mental health stressors such as depression, anxiety, low self-esteem, and social isolation. Not all gender nonconforming individuals experience gender dysphoria, and measuring a person's gender dysphoria is critical when considering medical intervention for gender nonconformity.
=== Modern era === In the 16th century Aquileia fell under the Habsburg County of Gorizia (later the Princely County of Gorizia and Gradisca), a part of the Holy Roman Empire. The patriarchal diocese was finally officially suppressed in 1751, and the sees of Udine and Gorizia were established from its territory. During the Napoleonic Wars Aquileia was annexed to the Napoleonic Kingdom of Italy by the 1807 Treaty of Fontainebleau. It returned to Austrian control in 1815 following the Congress of Vienna, initially as part of the Kingdom of Illyria, then the reconstituted Gorizia and Gradisca (part of the Austrian Littoral). Following the Austro-Hungarian defeat in World War I, Aquileia passed to the Kingdom of Italy in 1920 (Treaty of Rapallo).
Sources: en.wikipedia.org
Semax is based on the ACTH(4-10) fragment, a seven-amino-acid segment of adrenocorticotropic hormone. The synthetic peptide retains the core sequence while removing regions associated with endocrine activity. This modification is intended to isolate effects on the nervous system.
It is registered for clinical use in Russia and a few other countries, typically as a nasal drop formulation. It does not hold approval from the United States Food and Drug Administration or the European Medicines Agency. Outside those markets it is generally handled as a research chemical.
The compound was developed in Moscow and the earliest studies were conducted there, so the primary literature is largely in Russian-language journals. Translation and indexing have been incomplete, which limits access for outside researchers. Independent groups have since published some work, but the total volume remains modest.
Dry powder is usually kept at about -20 degrees Celsius for long-term storage and at 2 to 8 degrees Celsius for short working periods. Containers should stay sealed and protected from light and moisture to limit degradation.