melanocortin signalling comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Updated 2025-09-02. Numbers and descriptions here follow the published literature rather than marketing material.
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.
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. Its chain combines the first seven residues of corticotropin with a C-terminal proline-glycine-proline extension, a modification intended to slow enzymatic breakdown. The free peptide has a molecular mass near 813.9 daltons. It belongs to the class of ACTH-derived fragments studied for central nervous system activity rather than for adrenal steroid stimulation. This structural relationship to a natural hormone fragment is the usual starting point for describing the compound in the literature.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C37H51N9O10S | Free acid form of the heptapeptide; depends on terminal groups |
| Molecular mass | About 813.9 g/mol | Average mass used for mass spectrometry confirmation |
| Appearance | White to off-white solid | Supplied as a lyophilised powder; hygroscopic |
| Solubility class | Freely soluble in aqueous media | Water, saline, and phosphate buffers; limited organic solubility |
| Typical storage temperature | -20 degrees Celsius | Long term and dry; short working periods may use 2 to 8 degrees Celsius |
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.
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。
当时的短肽研究普遍关注能否穿越血脑屏障、在低剂量下产生中枢效应，Semax 属于这一路线。鼻内给药是其主要使用方式，俄语文献报道的适应症涵盖缺血性卒中、短暂性脑缺血发作、认知功能减退以及视神经病变。这些研究大多发表在当地期刊上，样本规模与终点设置同西方试验惯例存在差异，国际同行对其临床证据的强度看法不一。
Development of the compound took place in the Soviet Union during the 1980s, largely through peptide research groups affiliated with the Shemyakin-Ovchinnikov Institute and Moscow State University. Investigators screened fragments of adrenocorticotropic hormone for activity on the central nervous system while attempting to separate cognitive effects from hormonal ones. The shortened sequence was selected because it retained behavioral activity in animal models without stimulating corticosteroid release. Early publications described the molecule as an ACTH(4-10) analog.
Published research on this peptide originates mainly from Russian laboratories, and the wider international literature is comparatively thin. Studies have used rodent models of stroke, hypoxia, and memory tasks, with a smaller number of human trials reported. Reported outcomes include changes in attention and memory measures, along with effects on neurotrophic factor expression in some experiments. Small sample sizes, inconsistent dosing protocols, and limited independent replication are widely noted limitations, so the strength of the clinical evidence remains an open question.
The motor proteins actin and myosin generate the forces exerted by contracting muscles. Cortisol decreases amino acid uptake by muscle and inhibits protein synthesis. Current recommendations suggest that bodybuilders should consume 25–30% of protein per total calorie intake to further their goal of maintaining and improving their body composition. This is a widely debated topic, with many arguing that 1 gram of protein per pound of body weight per day is ideal, some suggesting that less is sufficient, while others recommending 1.5, 2, or more. It is believed that protein needs to be consumed frequently throughout the day, especially during/after a workout, and before sleep. There is also some debate concerning the best type of protein to take. Chicken, turkey, beef, pork, fish, eggs and dairy foods are high in protein, as are some nuts, seeds, beans, and lentils. Casein or whey are often used to supplement the diet with additional protein. Whey is the type of protein contained in many popular brands of protein supplements and is preferred by many bodybuilders because of its high biological value (BV) and quick absorption rates. Whey protein also has a bigger effect than casein on insulin levels, triggering about double the amount of insulin release. That effect is somewhat overcome by combining casein and whey.
== Discovery == In a screen for genes involved in apoptosis, Yasumasa Ishida, Tasuku Honjo and colleagues at Kyoto University in 1992 discovered and named PD-1. In 1999, the same group demonstrated that mice where PD-1 was knocked down were prone to autoimmune disease and hence concluded that PD-1 was a negative regulator of immune responses. In 2025, Yasumasa Ishida was part of a group that found that PD-1, together with its extracellular ligand "PD-L1" (the name given to the single gene precursor of both PD-L1 and PD-L2 genes in tetrapod species) and cytoplasmic tail binding phosphatases SHP-1 and SHP-2, and their interaction motifs, are well-conserved in evolution throughout jawed vertebrates (from the level of sharks) (Figure 2). This corroborated partial findings by others.
== Clinical significance == The members of the HtrA family of proteases have been shown playing critical roles in cell physiology and being involved in several pathological processes including cancer and neurodegenerative disease. Strong evidences supported HtrA2's involvement in oncogenesis. This protein is widely expressed in a variety of cancer cell lines, Analysis of biopsy samples showed changes in expression of HtrA2 in cancer tissues compared with normal tissues. HtrA2 has recently been identified as a gene related to Parkinson's disease. Mutations in Htra2 have been found in patients with Parkinson's disease. Additionally, mice lacking HtrA2 have a parkinsonian phenotype. This suggests that HtrA2 is linked to Parkinson's disease progression in humans and mice.
Sources: en.wikipedia.org
== Personal life == Yates lives in Marbella with his wife, Brazilian fitness model Glauce "Gal" Ferreira, whom he had met at the 2008 Arnold Classic. His son with his ex-wife Deb is also a bodybuilder and the two work closely together. Yates practises yoga every day and has described yoga and meditation as life-altering experiences. He has endorsed the use of psychedelics such as ayahuasca for religious and spiritual purposes. He is open about his cannabis use, which predates his bodybuilding career; in a July 2017 appearance on The Joe Rogan Experience, he stated that cannabis has "anti-cancer" properties and said that he is an advocate for its legalisation for this reason in addition to its relaxing properties and temporary increases in respiratory capacity. Yates revealed his belief in Holocaust denial theories whilst being interviewed by Dave Palumbo in April 2018, claiming that the Holocaust death toll had been "exaggerated" and that two forensic studies (which he did not provide the names of) had concluded that no gas was ever used at the Auschwitz concentration camp.
After finding out that Apoth was using children to disseminate a technological drug called Overclock, Mister Sinister modified Overclock to allow Psylocke to interact with Apoth in a cyberspace, killing Apoth, whose remains she delivered to Mister Sinister in exchange for his assistance in keeping this extrajudicial mission a secret from the Krakoan Quiet Council. Following the Apoth incident, Psylocke was assigned to monitor Mister Sinister's new team of Hellions, composed of mutants considered too violent or troubled to assimilate into Krakoan society. The character was later featured as a team member in the Marauders (vol. 2) as the team was refocused on their mission of mutant rescue. Following the fall of Krakoa, Kwannon headlined Psylocke (vol. 2), written by Alyssa Wong with art by Vincenzo Carratù, spun out of the events of Jed MacKay and Ryan Stegman's X-Men (vol. 7) where Kwannon was a team member.
It does not form a hydrate, unlike sodium sulfate. The salt crystallizes as double six-sided pyramids, classified as rhombic. They are transparent, very hard and have a bitter, salty taste. The salt is soluble in water, but insoluble in solutions of potassium hydroxide (sp. gr. 1.35), or in absolute ethanol.
Sources: en.wikipedia.org
==== United States ==== The US Food and Drug Administration (FDA) considers safe beverages containing less than 0.02% caffeine; but caffeine powder, which is sold as a dietary supplement, is unregulated. It is a regulatory requirement that the label of most prepackaged foods must declare a list of ingredients, including food additives such as caffeine, in descending order of proportion. However, there is no regulatory provision for mandatory quantitative labeling of caffeine, (e.g., milligrams caffeine per stated serving size). There are a number of food ingredients that naturally contain caffeine. These ingredients must appear in food ingredient lists. However, as is the case for "food additive caffeine", there is no requirement to identify the quantitative amount of caffeine in composite foods containing ingredients that are natural sources of caffeine. While coffee or chocolate are broadly recognized as caffeine sources, some ingredients (e.g., guarana, yerba maté) are likely less recognized as caffeine sources. For these natural sources of caffeine, there is no regulatory provision requiring that a food label identify the presence of caffeine nor state the amount of caffeine present in the food. The FDA guidance was updated in 2018.
Extremely strong: Histamine H1 receptor Strong: α1-adrenergic receptor, 5-HT2A and muscarinic acetylcholine receptors Moderate: 5-HT2C and 5-HT1A receptors Weak: α2-adrenergic and D2 receptors Based on its IC50Tooltip half-maximal inhibitory concentration values for monoamine reuptake inhibition, doxepin is relatively selective for the inhibition of norepinephrine reuptake, with a much weaker effect on the serotonin transporter. Although there is a significant effect that takes place at one of the specific serotonergic binding sites, the 5-HT2A serotonin receptor subtype. There is negligible influence on dopamine reuptake. The major metabolite of doxepin, nordoxepin (desmethyldoxepin), is pharmacologically active similarly, but relative to doxepin, is much more selective as a norepinephrine reuptake inhibitor. In general, the demethylated variants of tertiary amine TCAs like Nortriptyline, Desipramine and nordoxepin are much more potent inhibitors of norepinephrine reuptake, less potent inhibitors of serotonin reuptake, and less potent in their antiadrenergic, antihistamine, and anticholinergic activities. Antidepressant doses of doxepin are defined as 25 to 300 mg/day, although are typically above 75 mg/day. Antihistamine doses, including for dermatological uses and as a sedative/hypnotic for insomnia, are considered to be 3 to 25 mg, although higher doses between 25 and 50 mg and in some cases even up to 150 mg have been used to treat insomnia. At low doses, below 25 mg, doxepin is a pure antihistamine and has more of a sedative effect.
The component viral strains of MMR vaccine were developed by propagation in animal and human cells. For example, in the case of mumps and measles viruses, the virus strains were grown in embryonated chicken eggs. This produced strains of virus which were adapted for chicken cells and less well-suited for human cells. These strains are therefore called attenuated strains. They are sometimes referred to as neuroattenuated because these strains are less virulent to human neurons than the wild strains. The rubella component, Meruvax, was developed in 1967, through propagation using the human embryonic lung cell line WI-38 (named for the Wistar Institute) that was derived six years earlier in 1961.
Sources: en.wikipedia.org
It is described as a synthetic analogue of the ACTH(4–10) fragment, a short segment of adrenocorticotropic hormone. Its sequence differs from that fragment and includes two proline residues, which influence stability and behaviour in solution.
It appears in Russian pharmaceutical listings as a nasal formulation, but it is not an authorised medicine in the United States or the European Union. Outside those markets it is normally encountered as a research chemical rather than a prescription product.
Laboratory and animal work points to melanocortin signalling and changes in neurotrophic factor levels, especially brain-derived neurotrophic factor. The exact receptor targets and the degree to which these findings transfer to humans are still unresolved.
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.