If you have been reading about GABA-A modulation 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.
Updated 2025-08-22. Numbers and descriptions here follow the published literature rather than marketing material.
Published clinical work is concentrated in Russian-language journals and generally involves small samples without independent replication. Systematic reviews in English note the shortage of randomised, placebo-controlled trials and the difficulty of verifying methods from translated reports. Outcome measures vary between studies, which complicates pooling of results. Interest in the compound as a cognitive or anxiolytic agent therefore rests on a thinner evidence base than the volume of citations suggests. Replication in well-powered trials with preregistered endpoints would be needed before firm conclusions about efficacy can be drawn.
Proposed mechanisms centre on the GABAergic system. Animal and tissue studies report changes in GABA-A receptor expression and reduced activity of GABA transaminase, the enzyme that degrades GABA. Effects on monoamine turnover, including serotonin and dopamine pathways, are also described, and a separate line of work links the peptide to increased expression of brain-derived neurotrophic factor in hippocampal tissue. Most of these findings come from rodent models and cell preparations. How the individual observations combine into a single coherent mode of action is not settled.
Measuring peptide exposure inside the brain is technically difficult. Selank is degraded rapidly in plasma, and assays must separate intact peptide from fragments, which favors targeted mass spectrometry over immunoassays alone. Reported half-lives are short, on the order of minutes, so effects observed hours later are attributed to downstream signaling rather than to the parent compound. Blood-brain barrier permeability is debated and rarely quantified directly. Gaps include absent dose-response characterization, inconsistent reporting of purity, and almost no pharmacokinetic data from human participants.
Selank is studied chiefly as an animal-model anxiolytic with proposed secondary effects on memory and immune signaling. Reported mechanisms include modulation of the GABA-A receptor complex, inhibition of enkephalin-degrading enzymes, and shifts in monoamine turnover within limbic structures. Some experiments describe increased expression of brain-derived neurotrophic factor in the hippocampus after repeated dosing. No single molecular target has been confirmed, and the peptide does not bind any receptor with the selectivity typical of a conventional small-molecule drug. Mechanism therefore remains a set of hypotheses rather than an established pathway.
Laboratory work relies on standard behavioral paradigms. Rodents are tested in the elevated plus maze, open field, and passive avoidance tasks, with outcomes compared against diazepam or vehicle controls. Intranasal dosing is used most often because it bypasses first-pass metabolism, though intraperitoneal and intravenous routes also appear in published protocols. Biochemical endpoints include tissue BDNF concentrations, cytokine levels, and monoamine metabolites. Human data are limited to small Russian trials reporting reduced anxiety scores; most were not prospectively registered, and few employed independent outcome assessment.
| Property | Value | Notes |
|---|---|---|
| Primary route studied | Intranasal | Also examined parenterally in animal work |
| Reported plasma half-life | Minutes to tens of minutes | Values vary widely between reports |
| Main model systems | Rodent behavioural and cell assays | Human trials are few and small |
| Principal proposed targets | GABA-A receptor, GABA transaminase | Monoamine and neurotrophic pathways also reported |
| Evidence grade | Preliminary | Limited independent replication |
Animal studies have examined behaviour in tests of anxiety, memory retention and stress response, and several report changes in neurotrophic or neurotransmitter-related markers. The human evidence base is much smaller, consisting mainly of short trials conducted in Russia with limited reporting in English-language journals. Sample sizes are modest and outcome measures vary between studies, so the findings are best described as preliminary. Independent replication under modern trial standards has not been widely reported.
Outside its country of origin the compound is generally handled as a research chemical rather than an approved medicine. No regulatory approval from the United States Food and Drug Administration or the European Medicines Agency has been granted for human use. Identity and purity are normally checked by reverse-phase high-performance liquid chromatography, with mass spectrometry used to confirm the molecular mass. Lyophilised material is stored cold and desiccated, and repeated freeze-thaw cycles are avoided.
Published work on this peptide almost always uses intranasal delivery, with drops or a spray applied to the nasal mucosa. Some animal experiments have used subcutaneous or intraperitoneal injection, and a smaller number have compared routes directly. Oral administration is not a focus of the literature, because short peptides of this size are broken down by digestive enzymes and cross intestinal barriers poorly. How much of an intranasal dose reaches the bloodstream intact in humans remains an open question.
Enzymatic stability motivates the extra three residues at the carboxyl end. Native tuftsin is cleaved quickly by circulating aminopeptidases and carboxypeptidases, which limits its duration of action and its usefulness as a tool compound. Extending the chain with proline-rich segments is a common design tactic because proline constrains the backbone and slows proteolysis. The same Pro-Gly-Pro motif appears in other Russian-developed peptides of the era. Whether the full seven-residue chain is required for activity, or whether it acts mainly as a prodrug releasing tuftsin, remains unresolved.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. Its four N-terminal residues reproduce tuftsin, a tetrapeptide fragment of the immunoglobulin heavy chain, while the C-terminal Pro-Gly-Pro extension is a synthetic addition. The peptide has a molecular mass near 752 daltons and carries a net positive charge at physiological pH because of the arginine and lysine side chains. Published indexes list it under the name Selank and the sequence abbreviation TKPRPGP. Solid-phase peptide synthesis is the standard production route for research quantities.
Regulatory status differs sharply by region. Selank holds a Russian marketing authorization, where it is supplied mainly as nasal drops, while authorities elsewhere have not approved it for medical use. Material sold internationally is therefore usually labeled as a research chemical rather than a medicine. Peer-reviewed publications come predominantly from Russian laboratories, and sample sizes are generally small. Whether the compound produces comparable effects under independent, well-controlled replication remains an open question that the broader literature has not settled.
Selank is a synthetic heptapeptide developed in Russia as a structural analogue of tuftsin, a naturally occurring immunomodulatory tetrapeptide. Its sequence, Thr-Lys-Pro-Arg-Pro-Gly-Pro, keeps the tuftsin core at the N-terminus and appends a Pro-Gly-Pro tail. Researchers at the Institute of Molecular Genetics in Moscow synthesized the compound during the 1990s while searching for peptides with combined anxiolytic and immunomodulatory activity. The added tail was intended to resist enzymatic cleavage and prolong the molecule's presence in circulation.
Type B: onset at age 20 or older and duration of less than 10 years. Type C: onset at age 10–19 or duration of 10–19 years. Type D: onset before age 10 or duration greater than 20 years. Type E: overt diabetes mellitus with calcified pelvic vessels. Type F: diabetic nephropathy. Type R: proliferative retinopathy. Type RF: retinopathy and nephropathy. Type H: ischemic heart disease. Type T: prior kidney transplant. An early age of onset or long-standing disease comes with greater risks, hence the first three subtypes. Two other sets of criteria are available to diagnose gestational diabetes, both based on blood-sugar levels. Criteria for diagnosis of gestational diabetes, using the 100-gram Glucose Tolerance Test, according to Carpenter and Coustan:
== Biochemistry == DTPA is more effective than EDTA to deactivate redox-active metal ions such as Fe(II)/(III), Mn(II)/(IV) and Cu(I)/(II) perpetuating oxidative damages induced in cells by superoxide and hydrogen peroxide. DTPA is also used in bioassays involving redox-active metal ions.
Southern Rhodesia had long been distinctive among British dependencies in that it had financed and developed its own security forces and command structure. After UDI, this posed a particular dilemma for the British government, which considered and rejected various proposals aimed at ending Rhodesia's state of rebellion by force. Harold Wilson once remarked that bringing an end to Rhodesian independence "would not be a case of arresting a subversive individual. It would mean a bloody war, and probably a bloody war turning into a bloody civil war." The formidable nature of the Rhodesian security forces, as well as British fears of a direct South African intervention on behalf of the rogue colony, preempted the further consideration of military options. For much of its existence, Rhodesia maintained a small professional standing army of 3,400 troops, about a third of whom were black volunteers. In the tradition of many colonial armies, it was primarily organised into light infantry battalions trained and equipped for counter-insurgency warfare or internal security actions, and possessed little artillery or armour. The Royal Rhodesian Air Force (RRAF) had 1,000 personnel and six squadrons of aircraft, including forty to fifty Hawker Hunter and de Havilland Vampire strike aircraft and English Electric Canberra light bombers. It also possessed a helicopter squadron, a transport squadron, and a light reconnaissance squadron.
Bowfin eggs are adhesive, and attach to aquatic vegetation, roots, gravel, and sand. After hatching, larval bowfin do not swim actively in search of food. During the 7-9 days required for yolk-sac absorption, they attach to vegetation by means of an adhesive organ on their snout, and remain protected by the parent male bowfin. Bowfin aggressively protect their spawn from the first day of incubation to a month or so after the eggs have hatched. When the fry are able to swim and forage on their own, they form a school and leave the nest accompanied by the parent male bowfin, which slowly circles them to prevent separation. Bowfin reach sexually maturity at 2-3 years of age. They can live up to 30 years in captivity.
== See also == Control engineering Instrument and control engineering Functional safety Safety integrity level Oil refinery Piping and instrumentation diagram Process flow diagram Process manufacturing
Sources: en.wikipedia.org
=== CNO-I === The first proposed catalytic cycle for the conversion of hydrogen into helium was initially called the carbon–nitrogen cycle (CN-cycle), also referred to as the Bethe–Weizsäcker cycle in honor of the independent work of Carl Friedrich von Weizsäcker in 1937–38 and Hans Bethe. Bethe's 1939 papers on the CN-cycle drew on three earlier papers written in collaboration with Robert Bacher and Milton Stanley Livingston and which came to be known informally as Bethe's Bible. It was considered the standard work on nuclear physics for many years and was a significant factor in his being awarded the 1967 Nobel Prize in Physics. Bethe's original calculations suggested the CN-cycle was the Sun's primary source of energy. This conclusion arose from a belief that is now known to be mistaken, that the abundance of nitrogen in the sun is approximately 10%; it is actually less than half a percent. The CN-cycle, named as it contains no stable isotope of oxygen, involves the following cycle of transformations:
It is not clear if this term refers to IRP, rectal mucosal prolapse, or a mucosal prolapse which does not protrude externally. Mucosal prolapse has been defined as infolding of less than 3 mm of the thickness of the rectal wall. If the thickness of the prolapsed segment is more than 3 mm, the term intussusception is used.
=== Nuclear weapons === The Little Boy gun-type atomic bomb dropped on Hiroshima on August 6, 1945, was made of highly enriched uranium with a large tamper. A tamper is a layer of dense material surrounding the fissile material that delays its thermal expansion, keeping it supercritical for longer.The nominal spherical critical mass for an untampered 235U nuclear weapon is 56 kilograms (123 lb), which would form a sphere 17.32 centimetres (6.82 in) in diameter. The material must be 85% or more of 235U and is known as weapons grade uranium, though for a crude and inefficient weapon 20% enrichment is sufficient (called weapon(s)-usable). Even lower enrichment can be used, but this results in the required critical mass rapidly increasing. Use of a large tamper, implosion geometries, trigger tubes, polonium triggers, tritium enhancement, and neutron reflectors can enable a more compact, economical weapon using one-fourth or less of the nominal critical mass, though this would likely only be possible in a country that already had extensive experience in engineering nuclear weapons. Most modern nuclear weapon designs use plutonium-239 as the fissile component of the primary stage; however, HEU (highly enriched uranium, in this case uranium that is 20% or more 235U) is frequently used in the secondary stage as an igniter for the fusion fuel.
== Medical use == Exenatide is used to treat type 2 diabetes as an add-on to metformin, a biguanide, or a combination of metformin and a sulfonylurea, or thiazolidinediones such as pioglitazone. A 2011 Cochrane review showed a HbA1c reduction of 0.20% more with exenatide 2 mg compared to insulin glargine, exenatide 10 μg twice daily, sitagliptin and pioglitazone. Exenatide, lead to greater weight loss than glucagon-like peptide analogues. Due to shorter duration of studies, this review did not allow for long-term positive or negative effects to be assessed.
Sources: en.wikipedia.org
== Management == Nitroglycerin can be used immediately to dilate the venous system and reduce the circulating blood volume, therefore reducing the work and oxygen demand of the heart. In addition, nitroglycerin causes peripheral venous and artery dilation reducing cardiac preload and afterload. These reductions allow for decreased stress on the heart and therefore lower the oxygen demand of the heart's muscle cells. Antiplatelet drugs such as aspirin and clopidogrel can reduce platelet aggregation at the unstable atherosclerotic plaque, as well as combining these with an anticoagulant such as a low molecular weight heparin, can reduce clot formation.
In February 2023, Reuters reported that President Lula would meet with General Secretary of the Chinese Communist Party Xi Jinping during a four-day trip to China on 28 March to hold talks about trade, including green economy, digital inclusion, reindustrialization and the Russia-Ukraine War. On 17 March 2023, Itamaraty confirmed Lula's trip to China, adding that he would also meet with Chinese premier Li Qiang and National People's Congress chairman Zhao Leji. A week later, New Development Bank (NDB), whose headquarters are in Shanghai, elected Brazilian former president Dilma Rousseff as its new CEO after president Lula made his official appointment. On 24 March, however, due to health issues Lula canceled his trip which was later rescheduled for 11–14 April. As part of a separate high-level business forum between Brazilian and Chinese officials and hundreds of business people in Beijing, both countries announced on 29 March they were starting to trade in their own currencies (the Real and the Renmimbi) instead of in the US dollar. In April 2023, President Lula, who was accompanied by many of his cabinet ministers, Brazilian state governors and lawmakers, met with Chinese deputy foreign minister Xie Feng upon their arrival in Shanghai, where Lula also attended Brazilian former president Dilma Rousseff inauguration as the new NDB CEO, visited a Huawei center and spoke with several Chinese chairpeople including BYD CEO Wang Chuanfu and China Communications Construction Company (CCCC) CEO Wang Tongzhou.
=== Hereditary transthyretin-mediated amyloidosis === Inotersen received FDA approval for the treatment of hereditary transthyretin-mediated amyloidosis in October 2018. The application for inotersen was granted orphan drug designation. It was developed by Ionis Pharmaceuticals and licensed to Akcea Therapeutics. Patisiran (sold under Onpattro) was developed by Alnylam Pharmaceuticals, and also approved for use in the US and EU in 2018 with orphan drug designation. Its mechanism-of-action is the active substance of small interfering RNA (siRNA), which allows it to interfere with and block the production of transthyretin. As such, it was the first FDA-approved siRNA therapeutic.
Inhalation of tobacco smoke causes several immediate responses within the heart and blood vessels. Within one minute, the heart rate begins to rise, increasing by as much as 30 percent during the first 10 minutes of smoking. Carbon monoxide in tobacco smoke exerts negative effects by reducing the blood's oxygen-carrying ability. Smoking also increases the chance of heart disease, stroke, atherosclerosis, and peripheral artery disease. Several ingredients of tobacco lead to the narrowing of blood vessels, increasing the likelihood of a blockage, and thus a heart attack or stroke. According to a study by an international team of researchers, people under 40 are five times more likely to have a heart attack if they are smokers. Exposure to tobacco smoke is known to increase oxidative stress in the body by various mechanisms, including depletion of plasma antioxidants such as vitamin C. Research by American biologists has shown that cigarette smoke also influences the process of cell division in the cardiac muscle and changes the heart's shape. Smoking tobacco has also been linked to Buerger's disease (thromboangiitis obliterans), the acute inflammation and thrombosis (clotting) of arteries and veins of the hands and feet. Although cigarette smoking causes a greater increase in the risk of cancer than cigar smoking, people who smoke cigars still have an increased risk for many health problems, including cancer, when compared to people who do not smoke.
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Sources: en.wikipedia.org
Reports describe modulation of GABA signalling, changes in monoamine turnover and effects on neurotrophic factor expression. These observations come mainly from animal and cell studies. A single unifying mechanism has not been demonstrated.
The peptide enters plasma rapidly and is broken down by ordinary proteases into amino acids and shorter fragments. Reported half-lives are short. Whether meaningful amounts of the intact molecule reach the brain is an open question.
Most clinical reports are small, published in Russian and not independently replicated. English-language reviews highlight the absence of large randomised trials. Conclusions about efficacy should be treated as provisional.
Intranasal administration predominates in both animal and human research because it avoids hepatic first-pass metabolism. Injectable and intraperitoneal routes appear in animal work mainly for comparison.