If you have been reading about Neurotrophic signalling 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 2025-10-27. 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.
该化合物于二十世纪八十年代在俄罗斯被开发，相关工作由俄罗斯科学院分子遗传学研究所的研究团队主导。开发目标并非复制 ACTH 的完整激素活性，而是寻找保留其神经作用方向、同时去除促肾上腺皮质激素释放效应的短肽片段。研究记录显示，这一方向促成了多个相关短肽的合成与筛选，而 Semax 是其中被研究最广泛的一个。当地文献常以 Семакс 这一名称指代它。
研究兴趣主要集中在神经营养因子相关的路径上，包括脑源性神经营养因子与神经生长因子的表达变化。部分实验报告称在特定条件下观察到这些因子的水平上升，但具体信号通路和剂量依赖关系仍未完全厘清。多数公开数据来自细胞模型和动物实验，人体对照研究数量有限。因此，该化合物的作用机制在文献中属于活跃讨论，而非已经确立的定论。
| 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 |
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.
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. It was derived from the ACTH(4-10) fragment, a short segment of adrenocorticotropic hormone that lacks the hormonal activity associated with the full-length peptide. Researchers at the Institute of Molecular Genetics in Moscow developed the compound during the 1980s. It has been registered as a pharmaceutical product in Russia and several neighbouring countries, where it is supplied as a nasal solution, and it is also sold internationally as a research chemical.
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.
Laboratory descriptions of the material are consistent across suppliers. It appears as a white to off-white lyophilized powder that dissolves readily in water and in polar organic solvents such as dimethyl sulfoxide. Aqueous solutions are clear and colorless at low concentrations. Because the peptide contains methionine, oxidation at the sulfur atom is a recognized degradation pathway, and handling notes usually call for protected, desiccated storage. Reported purity for research-grade lots is generally above 95 percent as measured by reversed-phase high-performance liquid chromatography.
The compound is registered in Russia as a pharmaceutical product, most commonly formulated as a nasal solution, and has been used in that setting since the 1990s. Outside that jurisdiction it is generally handled as a research chemical rather than an approved medicine. Regulatory status therefore differs sharply between countries, and material sold internationally may not correspond to the Russian pharmaceutical formulation. Documentation with commercial samples is typically limited to a certificate of analysis covering purity and identity, not clinical status or local legal classification.
各国监管态度分化明显。俄罗斯按处方药管理，部分东欧国家留有使用记录；欧盟与美国未批准其作为药物上市，市面流通品通常标注为研究用化学品。身份差异意味着标示含量、纯度与无菌性缺少统一核查。体育领域还牵涉反兴奋剂名录，跨境携带则受目的地药品法规约束。
Semax 是人工设计的七肽，序列为 Met-Glu-His-Phe-Pro-Gly-Pro，骨架取自促肾上腺皮质激素片段 ACTH(4-10)。它于二十世纪八十年代在苏联的分子遗传学研究机构内合成。设计目标是保留该片段与注意力和记忆相关的活性，同时剔除促皮质激素释放等内分泌作用。此后俄罗斯将其登记为药品并进入临床使用。
The post-Arbenz government—a military junta headed by Carlos Castillo Armas—repealed a progressive land reform law, returned nationalized property belonging to the United Fruit Company, set up a National Committee of Defense Against Communism, and decreed a Preventive Penal Law Against Communism at the request of the United States. The non-aligned Indonesian government of Sukarno was faced with a major threat to its legitimacy beginning in 1956 when several regional commanders began to demand autonomy from Jakarta. After mediation failed, Sukarno took action to remove the dissident commanders. In February 1958, dissident military commanders in Central Sumatra (Colonel Ahmad Husein) and North Sulawesi (Colonel Ventje Sumual) declared the Revolutionary Government of the Republic of Indonesia-Permesta Movement aimed at overthrowing the Sukarno regime. They were joined by many civilian politicians from the Masyumi Party, such as Sjafruddin Prawiranegara, who were opposed to the growing influence of the communist Partai Komunis Indonesia. Due to their anti-communist rhetoric, the rebels received arms, funding, and other covert aid from the CIA until Allen Lawrence Pope, an American pilot, was shot down after a bombing raid on government-held Ambon in April 1958. The central government responded by launching airborne and seaborne military invasions of rebel strongholds at Padang and Manado. By the end of 1958, the rebels were militarily defeated, and the last remaining rebel guerilla bands surrendered by August 1961.
PDMPs allow pharmacists and prescribers to access patients' prescription histories to identify suspicious use. However, a survey of US physicians published in 2015 found only 53% of doctors used these programs, while 22% were not aware these programs were available. Following the implementation of pill mill laws and prescription drug monitoring programs in Florida, there was a large decline in opioid prescriptions written by high-risk prescribers (those prescribing the top 5th of opioids by volume). The Centers for Disease Control and Prevention (CDC) was tasked with establishing and publishing a new guideline, and was heavily lobbied. A 2018 study by the University of Florida concluded that there is little evidence that drug-monitoring databases are having a positive effect on the number of drug overdoses in the US. Researcher Chris Delcher also concluded that "there was a concurrent rise in fatal overdoses from fentanyl, heroin and morphine" due to ease of availability and lower cost following prescription drug crackdowns. The American Medical Association (AMA) has created an Opioid Task Force for helping physicians to combat the epidemic. The AMA has suggested 6 actions for physicians to take:
However, Gilbert syndrome can arise without TATA box promoter polymorphic variants; in some populations, particularly healthy Southeast and East Asians, Gilbert's syndrome is more often a consequence of heterozygote missense mutations (such as Gly71Arg also known as UGT1A1*6, Tyr486Asp also known as UGT1A1*7, Pro364Leu also known as UGT1A1*73) in the actual gene coding region, which may be associated with significantly higher bilirubin levels. Because of its effects on drug and bilirubin breakdown and because of its genetic inheritance, Gilbert's syndrome can be classed as a minor inborn error of metabolism.
Carbohydrate catabolism is the breakdown of carbohydrates into smaller units. Carbohydrates are usually taken into cells after they have been digested into monosaccharides such as glucose and fructose. Once inside, the major route of breakdown is glycolysis, in which glucose is converted into pyruvate. This process generates the energy-conveying molecule NADH from NAD+, and generates ATP from ADP for use in powering many processes within the cell. Pyruvate is an intermediate in several metabolic pathways, but the majority is converted to acetyl-CoA and fed into the citric acid cycle, which enables more ATP production by means of oxidative phosphorylation. This oxidation consumes molecular oxygen and releases water and the waste product carbon dioxide. When oxygen is lacking, or when pyruvate is temporarily produced faster than it can be consumed by the citric acid cycle (as in intense muscular exertion), pyruvate is converted to lactate by the enzyme lactate dehydrogenase, a process that also oxidizes NADH back to NAD+ for re-use in further glycolysis, allowing energy production to continue. The lactate is later converted back to pyruvate for ATP production where energy is needed, or back to glucose in the Cori cycle. An alternative route for glucose breakdown is the pentose phosphate pathway, which produces less energy but supports anabolism (biomolecule synthesis). This pathway reduces the coenzyme NADP+ to NADPH and produces pentose compounds such as ribose 5-phosphate for synthesis of many biomolecules such as nucleotides and aromatic amino acids.
Sources: en.wikipedia.org
== External links == Clinical trial number NCT02290873 for "A Phase III Study of the Efficacy and Safety of Remimazolam Compared to Placebo and Midazolam in Colonoscopy Patients" at ClinicalTrials.gov Clinical trial number NCT02296892 for "A Phase III Study of Remimazolam in Patients Undergoing Bronchoscopy" at ClinicalTrials.gov Clinical trial number NCT02532647 for "Safety and Efficacy of Remimazolam in ASA III and IV Patients Undergoing Colonoscopy" at ClinicalTrials.gov
== Causes == AMR is driven largely by the misuse and overuse of antimicrobials. They reproduce and spread quickly, and they also can adapt to their environment and change how well they can survive. Yet, at the same time, many people do not have access to essential antimicrobials. This leads to microbes either evolving a defense against drugs used to treat them, or certain strains of microbes that have a natural resistance to antimicrobials becoming much more prevalent than the ones that are easily defeated with medication. Genetic changes can also occur, which would allow the microbe to survive. While antimicrobial resistance does occur naturally over time, the use of antimicrobial agents in a variety of settings both within the healthcare industry and outside of has led to antimicrobial resistance becoming increasingly more prevalent. Although many microbes develop resistance to antibiotics over time through natural mutation, overprescribing and inappropriate prescription of antibiotics have accelerated the problem. During mutation, when replication happens, these mutations help individual microbes survive exposure. It is possible that as many as 1 in 3 prescriptions written for antibiotics are unnecessary. Every year, approximately 154 million prescriptions for antibiotics are written. Of these, up to 46 million are unnecessary or inappropriate for the condition that the patient has.
=== 1940s === During and after World War II, the field of biomedical science saw a new age of technology and treatment methods. For instance in 1941 the first hormonal treatment for prostate cancer was implemented by Urologist and cancer researcher Charles B. Huggins. Huggins discovered that if you remove the testicles from a man with prostate cancer, the cancer had nowhere to spread, and nothing to feed on thus putting the subject into remission. This advancement lead to the development of hormonal blocking drugs, which is less invasive and still used today. At the tail end of this decade, the first bone marrow transplant was done on a mouse in 1949. The surgery was conducted by Dr. Leon O. Jacobson, he discovered that he could transplant bone marrow and spleen tissues in a mouse that had both no bone marrow and a destroyed spleen. The procedure is still used in modern medicine today and is responsible for saving countless lives.
== Isotopomer and isotopologue == Isotopomers (isotopic isomers) are isomers having the same number of each isotopic atom, but differing in the positions of the isotopic atoms. For example, CH3CHDCH3 and CH3CH2CH2D are a pair of structural isotopomers. Isotopomers should not be confused with isotopologues, which are chemical species that differ in the isotopic composition of their molecules or ions. For example, three isotopologues of the water molecule with different isotopic composition of hydrogen are: HOH, HOD and DOD, where D stands for deuterium (2H).
In 1842, John Gorrie created a system capable of refrigerating water to produce ice. Although it was a commercial failure, it inspired scientists and inventors around the world. France's Ferdinand Carre was one of the inspired and he created an ice producing system that was simpler and smaller than that of Gorrie. During the Civil War, cities such as New Orleans could no longer get ice from New England via the coastal ice trade. Carre's refrigeration system became the solution to New Orleans' ice problems and, by 1865, the city had three of Carre's machines. In 1867, in San Antonio, Texas, a French immigrant named Andrew Muhl built an ice-making machine to help service the expanding beef industry before moving it to Waco in 1871. In 1873, the patent for this machine was contracted by the Columbus Iron Works, a company acquired by the W.C. Bradley Co., which went on to produce the first commercial ice-makers in the United States. By the 1870s, breweries had become the largest users of harvested ice. Though the ice-harvesting industry had grown immensely by the turn of the 20th century, pollution and sewage had begun to creep into natural ice, making it a problem in the metropolitan suburbs. Eventually, breweries began to complain of tainted ice. Public concern for the purity of water, from which ice was formed, began to increase in the early 1900s with the rise of germ theory. Numerous media outlets published articles connecting diseases such as typhoid fever with natural ice consumption. This caused ice harvesting to become illegal in certain areas of the country.
Sources: en.wikipedia.org
==== Biomolecular mechanisms ==== Chronic use of amphetamine at excessive doses causes alterations in gene expression in the mesocorticolimbic projection, which arise through transcriptional and epigenetic mechanisms. The most important transcription factors that produce these alterations are Delta FBJ murine osteosarcoma viral oncogene homolog B (ΔFosB), cAMP response element binding protein (CREB), and nuclear factor-kappa B (NF-κB). ΔFosB is the most significant biomolecular mechanism in addiction because ΔFosB overexpression (i.e., an abnormally high level of gene expression which produces a pronounced gene-related phenotype) in the D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and regulates multiple behavioral effects (e.g., reward sensitization and escalating drug self-administration) involved in addiction. Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression. It has been implicated in addictions to alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others. ΔJunD, a transcription factor, and G9a, a histone methyltransferase enzyme, both oppose the function of ΔFosB and inhibit increases in its expression. Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).
=== Fat === In 1949, purified insulin was shown to regenerate fat in diabetics with lipoatrophy. In 1976, after 82 days of consecutive injections into a scar, purified insulin was shown to safely regenerate fat and completely regenerate skin in a non-diabetic. During a high-fat diet, and during hair follicle growth, mature adipocytes (fats) are naturally formed in multiple tissues. Fat tissue has been implicated in the inducement of tissue regeneration. Myofibroblasts are the fibroblast responsible for scar and in 2017 it was found that the regeneration of fat transformed myofibroblasts into adipocytes instead of scar tissue. Scientists also identified bone morphogenetic protein (BMP) signalling as important for myofibroblasts transforming into adipocytes for the purpose of skin and fat regeneration.
=== Hydroxykynureninuria === Also known as kynureninase deficiency, this extremely rare inherited disorder is caused by the defective enzyme kynureninase which leads to a block in the pathway from tryptophan to nicotinic acid mononucleotide (NaMN). As a result, tryptophan is no longer a source of niacin, hence not producing NAD, leading to pellagra (niacin deficiency). Both B6-responsive and B6-unresponsive forms are known. Patients with this disorder excrete excessive amounts of xanthurenic acid, kynurenic acid, 3-hydroxykynurenine, and kynurenine after tryptophan loading and are said to suffer from tachycardia, irregular breathing, arterial hypotension, cerebellar ataxia, developmental retardation, coma, renal tubular dysfunction, renal or metabolic acidosis, and even death. The only biochemical abnormality noted in affected patients was a massive hyperkynureninuria, seen only during periods of coma or after intravenous protein loading. This disturbance was temporarily corrected by large doses of vitamin B6. The activity of kynureninase in the liver was markedly reduced. The activity was appreciably restored by the addition of pyridoxal phosphate.
== History == The first use of epitope tagging was described by Munro and Pelham in 1984. The FLAG-tag was the second example of a fully functional, improved epitope tag, published in the scientific literature. and was the only epitope tag to be patented. It has since become one of the most commonly used protein tags in laboratories worldwide. Unlike some other tags (e.g. myc, HA), where a monoclonal antibody was first isolated against an existing protein, then the epitope was characterized and used as a tag, the FLAG epitope was an idealized, artificial design, to which monoclonal antibodies were raised. The FLAG-tag's sequence was optimized for compatibility with proteins it is attached to, in that FLAG-tag is more hydrophilic than other common epitope tags and therefore less likely to reduce the activity of proteins to which FLAG-tag is appended. In addition, N-terminal FLAG tags can be removed readily from proteins once they have been isolated, by treatment with the specific protease, enterokinase (enteropeptidase). The third report of epitope tagging, (HA-tag), appeared about one year after the Flag system had been first shipped.
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.
不是。Semax 是完全人工合成的七肽，自然界中没有对应的已知肽段。它的设计灵感来自促肾上腺皮质激素片段 ACTH(4-10)，但序列经过了替换和延长。