This is a working overview of elevated plus maze, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-10-19. Anything still debated is marked as such rather than presented as settled.
Quantification in biological matrices relies on liquid chromatography coupled to tandem mass spectrometry with stable-isotope internal standards. Low plasma concentrations and adsorption to container surfaces both complicate measurement. Solid-phase extraction is often needed to reduce matrix interference before injection. Reported limits of quantification differ widely between laboratories, which makes direct comparison of pharmacokinetic results difficult and limits meta-analysis.
Peptide bonds are vulnerable to protease attack, and Selank is no exception. Measured half-life in serum is short, on the order of minutes in several reports, which explains why intranasal administration is the common route described in the literature. Absorption across the nasal mucosa partially bypasses first-pass hepatic metabolism. Quantitative data on human bioavailability remain limited and are difficult to compare across studies.
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 |
|---|---|---|
| Dry storage temperature | -20 C or below | Sealed, desiccated, protected from light |
| Solution stability | Hours to days at 2-8 C | Depends on buffer and microbial load |
| Preferred pH range | Near neutral to slightly acidic | Alkaline pH accelerates hydrolysis |
| Main degradation routes | Hydrolysis and deamidation | No cysteine or methionine in sequence |
| Identity confirmation | Electrospray mass spectrometry | Observed mass compared with 751.9 Da |
Proposed mechanisms centre on modulation of the GABAergic system, with reports of altered expression of genes related to GABA-A receptor subunits and changed monoamine turnover. Some studies describe inhibition of enkephalinase, the enzyme that degrades endogenous enkephalins, which may prolong opioid peptide signalling. Effects on brain-derived neurotrophic factor and on cytokine expression have also been reported. These findings come largely from animal models and small human studies, and the precise primary target remains unresolved.
Published clinical evidence is limited. Most controlled trials were conducted in Russia, enrolled modest numbers of participants, and appeared in Russian-language journals, which restricts independent verification. Reported outcomes include lower anxiety scores, improved attention and memory measures, and changes in fatigue ratings. Reviews written in English note methodological limitations such as small samples and inconsistent endpoints. Whether the compound produces clinically meaningful benefit relative to established anxiolytics is therefore an open question rather than an established finding.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It was designed at the Institute of Molecular Genetics of the Russian Academy of Sciences as a structural analogue of tuftsin, a naturally occurring tetrapeptide fragment of the immunoglobulin heavy chain. The added Pro-Gly-Pro tail was intended to slow enzymatic degradation and extend biological activity. In Russia it is registered as an anxiolytic nasal preparation, while regulators elsewhere have not approved it for clinical use.
Purity assessment relies mainly on reverse-phase high-performance liquid chromatography with ultraviolet detection. Because the peptide lacks a strong chromophore, detection often uses backbone absorbance near 214 nm. Identity is confirmed by mass spectrometry, typically electrospray ionization or matrix-assisted laser desorption, comparing the measured mass against the expected value. Amino acid analysis can verify composition after acid hydrolysis. Diastereomer content and residual counterions are reported less often, although both can influence biological assays.
Lyophilized material is generally stable for extended periods when kept dry at or below minus twenty degrees Celsius. Working solutions are less stable, and common practice is to aliquot and freeze them so that repeated freeze-thaw cycles are avoided. Aqueous solutions are sensitive to pH extremes and to microbial growth, so short-term storage at refrigerator temperature is typical. Oxidation and hydrolysis are the principal degradation routes. Reconstitution with sterile water or a mild buffer is standard, and solutions should be protected from light.
Regulatory treatment varies by jurisdiction. In Russia the compound is a registered prescription product, while in the European Union and the United States it is generally handled as a research chemical without a marketing authorization. Suppliers therefore operate outside pharmaceutical oversight, and buyers rely on supplier documentation for purity and identity claims. Chain of custody and third-party testing are the main verification tools. Analysts note that the absence of a pharmacopoeial monograph for research-grade material limits standardization across vendors.
Dry powder is normally held at -20 degrees Celsius or lower, in a sealed container with desiccant and protection from light. Reconstituted solutions are usually kept at 2 to 8 degrees Celsius for short periods and frozen for longer ones. Proline residues at several positions are generally associated with some resistance to peptidase attack, but chemical stability still declines at neutral to alkaline pH and at elevated temperature. Exact shelf-life figures are product-specific and are not standardised across suppliers.
Identity and purity are usually assessed by reversed-phase high-performance liquid chromatography, with mass spectrometry used to confirm molecular mass and sequence information. Amino acid analysis and peptide mapping may supplement these methods. Certified reference standards are scarce, and many commercial lots are sold as research chemicals without a pharmacopoeial monograph. Regulatory treatment differs by country: Selank is a registered prescription medicine in Russia, while in the European Union and the United States it is not an approved drug and may fall under research-chemical or unapproved-product frameworks.
Selank is a hydrophilic peptide and dissolves readily in water and in aqueous buffers. The lyophilised powder is typically a white to off-white solid. Because short peptides are prone to hydrolysis and oxidation, handling benefits from limiting exposure to heat, moisture and strong light. Working solutions are commonly prepared in sterile water or saline, and repeated freeze-thaw cycles are avoided to reduce aggregation and loss of activity. These practices reflect general laboratory convention rather than published stability specifications.
== Cold CNO cycles == Under typical conditions found in stars, catalytic hydrogen burning by the CNO cycles is limited by proton captures. Specifically, the timescale for beta decay of the radioactive nuclei produced is faster than the timescale for fusion. Because of the long timescales involved, the cold CNO cycles convert hydrogen to helium slowly, allowing them to power stars in quiescent equilibrium for many years.
=== Discontinued === 2-BUMP – monoamine oxidase B (MAO-B) inhibitor [238] A-77636 – dopamine D1 receptor agonist [239] Acamprosate/baclofen (PXT-864) – combination of acamprosate (various actions) and baclofen (GABAB receptor agonist) [240] Adrogolide (ABT-431; DAS-431; A-86929 O,O′-diacetate) – dopamine D1 receptor agonist (prodrug of A-86929) [241] AP-001 – various actions [242] Apomorphine inhalation (VR-004; VR-040; VR-400) – non-selective dopamine receptor agonist and other actions [243] Apomorphine intranasal – non-selective dopamine receptor agonist and other actions [244] Apomorphine subcutaneous (ND-0701) – non-selective dopamine receptor agonist and other actions [245] Apomorphine transdermal patch – non-selective dopamine receptor agonist and other actions [246] Arimoclomol (BRX-345; Miplyffa; OR-01; OR-04) – undefined mechanism of action [247] Arundic acid (Arocyte Injection; Cereact Capsule; MK-0724; ONO-2506; Proglia) – various actions [248] Atomoxetine (LY-139603; Strattera; Tomoxetine) – norepinephrine reuptake inhibitor (NRI) [249] AVE-8112 (AVE8112; AVE-8112A) – phosphodiesterase PDE4 inhibitor [250] AX-201 (AX201) – nerve growth factor (NGF) stimulant [251] Bifeprunox (DU-127090) – serotonin 5-HT1A receptor agonist and dopamine D2 receptor agonist [252] BP-897 – dopamine D3 receptor agonist [253] Carbidopa/levodopa (AP-09004; AP-CD/LD) – combination of carbidopa (aromatic L-amino acid decarboxylase (AAAD) inhibitor) and levodopa (dopamine precursor) [254] CEP-1347 (KT-7515) – mitogen-activated protein kinase inhibitor and mixed-lineage kinase inhibitor [255] CERE-120 (AAV-NRTN; AAV-NTN; AAV2-neurturin; AAV2-NTN; neurturin gene therapy) – gene therapy, nerve tissue protein modulator, and neurturin agonist [256] Cinpanemab (BIIB-054) – monoclonal antibody against α-synuclein [257] CVXL-0107 – glutamate release inhibitor [258] Dactolisib (BEZ-235; NVP-BEZ-235; NVP-BEZ235-ANA; NVP-BEZ235-NX; RTB-101) – 1-phosphatidylinositol 3 kinase inhibitor and mTOR inhibitor [259] Davunetide intranasal (AL-108; NAP; NAPVSIPQ) – various actions [260] Dihydrexidine (DAR-0100) – dopamine D1 receptor agonist [261] Dihydrexidine (IP-202) – dopamine D1 and D5 receptor agonist [262] DNS-7801 – undefined mechanism of action [263] Embryonic neural cell therapy-Parkinson's Disease - CellFactors (Parkinson's disease cell therapy) – dopaminergic cell replacement [264] Emlenoflast (inzomelid; IZD-174; MCC-7840) – NLR family pyrin domain containing 3 (NLRP3) inhibitor [265] Entacapone (Comtan; Comtess; OR-611) – catechol O-methyltransferase (COMT) inhibitor [266] Ethyl eicosapentaenoic acid (AMR-101; Ethyl-EPA; LAX-101; Miraxion; Vascepa; Vazkepa) – various actions [267] Etrabamine (14-839JL; JL-14839) – dopamine D2 receptor agonist [268] Ezaladcigene resoparvovec (AAV-AADC; AV-201; GZ-404477; NBIb-1817) – gene transference and aromatic-L-amino-acid decarboxylase (AAAD) replacement [269] Fipamezole (BVF-025; JP-1730) – α2-adrenergic receptor antagonist [270] Florbenazine F18 (18F-DTBZ; 18F-AV-133; 18F-FP-dihydrotatetrabenazine; AV-133) – vesticular monoamine transporter 2 (VMAT2) inhibitor and radiopharmaceutical – diagnosis [271] Foliglurax (PXT-2331; PXT002331) – metabotropic glutamate mGlu4 receptor positive allosteric modulator [272] FRM-0334 (EVP-0334) – class I and class II histone deacetylase inhibitor [273] GYKI-52895 – dopamine reuptake inhibitor (DRI) [274] Levetiracetam (Keppra; L-059; SIB-S1; UCB-059; UCB-22059; UCB-L059) – synaptic vesicle glycoprotein 2A (SV2A) modulator [275] Lu-AA47070 (LU-AA-47070) – adenosine A2A receptor antagonist [276] Methylthioninium chloride (MTC; methylene blue; TRx-0014; TRx-014) – various actions [277] Naxagolide (L-647339) – dopamine D2 and D3 receptor agonist [278] Nebicapone (BIA-3202) – catechol O-methyltransferase (COMT) inhibitor [279] Nitecapone (OR-462) – catechol O-methyltransferase (COMT) inhibitor Nitisinone (NTBC; Orfadin; SC-0735; SYN-118) – 4-hydroxyphenylpyruvate dioxygenase inhibitor and dopamine release stimulant [280] NPT-088 (NPT088) – immunoglobulin fusion general amyloid interaction motif (GAIM) based dimer [281] NPT-189 (NPT189) – immunoglobulin fusion protein [282] NW-1048 – monoamine oxidase B (MAO-B) inhibitor [283] NYX-458 – ionotropic glutamate NMDA receptor positive allosteric modulator [284] ODM-103 – catechol O-methyltransferase (COMT) inhibitor [285] Omigapil (CGP-3466; SNT-317; TCH-346) – glyceraldehyde 3 phosphate dehydrogenase (GAPDH) inhibitor [286] OPM-201 (S-221237) – leucine-rich repeat kinase 2 (LRRK2) inhibitor [287] OSU-6162 (OSU6162; PNU-9639; PNU-96391; PNU-96391A) – serotonin 5-HT2A receptor partial agonist (non-hallucinogenic), dopamine D2 receptor partial agonist, and sigma σ1 receptor ligand (so-called "monoaminergic stabilizer") [288] Paliroden (SR-57667; SR-57667B) – nerve growth factor (NGF) stimulant [289] Pardoprunox (SLV-308; SME-308) – dopamine D2 and D3 receptor partial agonist, serotonin 5-HT1A receptor full agonist, and other actions [290] Parkinson's disease gene therapy - Oxford BioMedica (AXO Lenti PD; OXB-101; OXB-102; ProSavin) – gene transference [291] Pegipanermin (DN-TNF; INB-03; LIVNate™; Quellor™; soluble tumour necrosis factor inhibitor; XENP1595; XENP345; XPro 1595; XPro595; XProTM) – tumour necrosis factor alpha (TNFα) inhibitor and immunostimulant [292] PF-06412562 (CVL-562) – dopamine D1 and D5 receptor partial agonist [293] Piclozotan (SUN-4057; SUN-N-4057) – serotonin 5-HT1A receptor agonist – dyskinesia in Parkinson's disease [294] Preclamol ((–)-3-PPP) – dopamine D2 receptor partial agonist [295] Preladenant (MK-3814; privadenant; SCH-420814) – adenosine A2A receptor antagonist [296] Proxison – synthetic flavonoid-based antioxidant [297] Quinelorane (LY-163502) – dopamine D2 receptor agonist [298] Raseglurant (ADX-10059) – metabotropic glutamate mGlu5 receptor negative allosteric modulator [299] Razpipadon (CVL-871; PF-6669571; PF-06669571; PW-0464) – dopamine D1 receptor agonist [300] Renzapride (ATL-1251; AZM-112; BRL-24924) – serotonin 5-HT3 receptor antagonist and serotonin 5-HT4 receptor agonist [301] Research programme: Alzheimer's and Parkinson's disease diagnostic agents - Bayer HealthCare Pharmaceuticals/TauRx – undefined mechanism of action – diagnosis [302] Research programme: AMC therapeutics - Animuscure – undefined mechanism of action [303] Research programme: Ig fusion GAIM dimers - Proclara Biosciences (NPT-288; NPT-007; NPT-014; NPT-289) – various actions [304] Research programme: Parkinson's disease therapeutics - Araclon Biotech (AB-03) – undefined mechanism of action [305] Research programme: Parkinson's disease therapies - Neose/Neuronyx – undefined mechanism of action [306] Research programme: Parkinson's disease therapies - Proteome Systems (EUK-418) – free radical scavenger and oxygen radical scavenger [307] Research programme: Parkinson's disease therapeutics - TauRx Therapeutics (G2 PD; TRx 018) – synuclein inhibitor [308] Research programme: protein aggregation inhibitors - Proclara Biosciences (NPT-001; NPT-002) – various actions [309] Riluzole (PK-26124; Rilutek; RP-54274) – various actions [310] Ropinirole implant – dopamine D2, D3, and D4 receptor agonist [311] Sarsasapogenin (Cogane; JNX-1001; PYM-50028; Smilagenin) – various actions [312] Sipagladenant (KW-6356) – adenosine A2A receptor antagonist [313] SPD-474 – undefined mechanism of action [314] Sumanirole (PNU-95666; U-95666) – dopamine D2 receptor agonist [315] TAK-065 – undefined mechanism of action [316] TAK-071 – muscarinic acetylcholine M1 receptor positive allosteric modulator [317] Tc 99m TRODAT-1 – single-photon emission-computed tomography (SPECT) enhancer – diagnosis [318] Terguride (Dironyl; Mysalfon; SH-406; Teluron; transdihydrolisuride; VUFB-6638; ZK-31224) – dopamine D2 receptor agonist and other actions [319] Tozadenant (A2a-(3); RO4494351; SYN-115) – adenosine A2A receptor antagonist [320] Utreloxastat (EPI-857; PTC-857) – 15-lipoxygenase (15-LOX/ALOX15) inhibitor [321] Vipadenant (BG-14; BIIB-014; BIIB14; CEB-4520; V-2006; VER-11135; VER-A00-11; VER-A00049; VER-ADO-49; VR-2006) – adenosine A2A receptor antagonist [322] [323]
== Indications == DBNPA is used as a disinfectant, bactericide, algicide, slime remover, and mildew inhibitor in several industrial applications. It is frequently used to regulate the growth of bacteria, algae, and slime in oilfield water injection systems and circulating cooling water systems. DBNPA is used in the paper industry as a slime remover, bactericide, and algicide to keep machinery free of microorganisms and maintain product quality. Additionally, it is utilized as a preservative to prevent microbiological deterioration in paints, waxes, inks, detergents, surfactants, slurries, and resins. DBNPA also serves as a fungicide and algaecide in municipal water landscapes, guaranteeing water safety and clarity, and as a biocide in process water and air purifier systems in the machinery manufacturing sector. The concentration used when it is being used as a water treatment slime stripper is 30~50 mg/L. When it is being used for water treatment, as a bactericide, it is used at a concentration of 10~20 mg/L. In terms of analytical detection in industrial and environmental samples, high-performance liquid chromatography with UV detection, measuring absorption at 230 nm, detects DBNPA at extremely low concentrations (>0.1 mg/L) in water samples. Gas chromatography-mass spectrometry can also identify and quantify DBNPA and the associated degradation products, (detection limit is 0.05 mg/L) in environmental samples.
Sources: en.wikipedia.org
=== Detection in body fluids === Acetylfentanyl may be quantitated in blood, plasma, or urine by liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Postmortem peripheral blood acetylfentanyl concentrations have been in a range of 89–945 μg/L in victims of acute overdosage.
The study also found that, in contrast, treatment of transgender women with estrogen and CPA (which is progestogenic in addition to antiandrogenic, unlike NSAAs) resulted in full lobuloalevolar development, as well as pregnancy-like breast hyperplasia in two of the subjects. In addition, it was observed that the lobuloalveolar maturation reversed upon discontinuation of CPA after sex reassignment surgery in these individuals. It was concluded that progestogen in addition to antiandrogen/estrogen treatment is required for the induction of full female histological breast development (i.e., that includes complete lobuloalveolar maturation), and that continued progestogen treatment is necessary to maintain such maturation. It should be noted however that although these findings may have important implications in the contexts of lactation and breastfeeding, epithelial tissue accounts for approximately only 10% of breast volume (with the bulk of the breasts (80–90%) being represented by stromal or adipose tissue), and it is uncertain to what extent, if any, that development of lobuloalveolar structures (a form of epithelial tissue) contributes to breast size and/or shape.
== Further reading == Albert, A.; Serjeant, E.P. (1971). The Determination of Ionization Constants: A Laboratory Manual. Chapman & Hall. ISBN 0-412-10300-1. (Previous edition published as Ionization constants of acids and bases. London (UK): Methuen. 1962.) Atkins, P.W.; Jones, L. (2008). Chemical Principles: The Quest for Insight (4th ed.). W.H. Freeman. ISBN 978-1-4292-0965-6. Housecroft, C. E.; Sharpe, A. G. (2008). Inorganic Chemistry (3rd ed.). Prentice Hall. ISBN 978-0-13-175553-6. (Non-aqueous solvents) Hulanicki, A. (1987). Reactions of Acids and Bases in Analytical Chemistry. Horwood. ISBN 0-85312-330-6. (translation editor: Mary R. Masson) Perrin, D.D.; Dempsey, B.; Serjeant, E.P. (1981). pKa Prediction for Organic Acids and Bases. Chapman & Hall. ISBN 0-412-22190-X. Reichardt, C. (2003). Solvents and Solvent Effects in Organic Chemistry (3rd ed.). Wiley-VCH. ISBN 3-527-30618-8. Chapter 4: Solvent Effects on the Position of Homogeneous Chemical Equilibria. Skoog, D.A.; West, D.M.; Holler, J.F.; Crouch, S.R. (2004). Fundamentals of Analytical Chemistry (8th ed.). Thomson Brooks/Cole. ISBN 0-03-035523-0.
=== Non-pharmacological treatments === A multi-disciplinary care team is often used in the treatment of JIA. One of the ways occupational or physical therapists help young children with JIA is by developing a home therapy program based around play. Exercises are prescribed by both physical therapists and occupational therapists to increase the range a child can move a joint, to strengthen the muscles around a joint, to decrease pain and stiffness and to prevent further limitations in their joint movements. OTs and PTs can provide children with age-appropriate games and activities to allow the children to practice their exercises while playing and socializing with friends. Examples are crafts, swimming, and sports. Surgery is only used to treat the most severe cases of JIA and is now rarely required.
Sources: en.wikipedia.org
The law outlawed closed shops which were contractual agreements that required an employer to hire only labor union members. Union shops, still permitted, require new recruits to join the union within a certain amount of time. The National Labor Relations Board and the courts have added other restrictions on the power of unions to enforce union security clauses and have required them to make extensive financial disclosures to all members as part of their duty of fair representation. On the other hand, Congress repealed the provisions requiring a vote by workers to authorize a union shop a few years after the passage of the act when it became apparent that workers were approving them in virtually every case.
=== Mating === Males attract females by singing via stridulation. An interested female will respond singing a similar-sounding song. The male will respond to the female by singing again. This can continue until copulation or the female becomes disinterested. Although a female response to male song does not guarantee mating it does increase the likelihood of copulation. Upon contact the male will produce a soft song and mount the female.
== Overview == Generally, it is considered that a hyperbolic structured protein in specific media conditions is ready to do its task, it is active, but some specific deactivation, are responsible for the regulation of some metabolism pathways. Regulatory enzymes are commonly the first enzyme in a multienzyme system: the product of the reaction catalyzed by the first enzyme is the substrate of the second enzyme, so the cell can control the amount of resulting product by regulating the activity of the first enzyme of the pathway. There are many strategies of activation and deactivation of regulatory enzymes. Regulatory enzymes require an extra activation process and need to pass through some modifications in their 3D in order to become functional, for instance, catalyzing enzymes (regulatory enzymes). The regulation of the activation of these catalyzing enzymes is needed in order to regulate the whole reaction speed, so that it is possible to obtain the amount of product required at any time, that makes regulatory enzymes have a biological importance. Therefore, regulatory enzymes, by its controlled activation and are of two types: allosteric enzymes and covalently modulated enzymes; however, an enzyme can combine both types of regulation.
Sources: en.wikipedia.org
Dry powder is best kept sealed, protected from light, and held at minus 20 degrees Celsius or below. Desiccant packaging helps limit moisture uptake because the material is hygroscopic. A sealed vial should be allowed to equilibrate to room temperature before opening to reduce condensation.
Hydrolysis of peptide bonds and deamidation of arginine and proline residues are the main degradation routes. Alkaline pH and higher temperatures accelerate both processes. Buffered, near-neutral solutions stored cold generally degrade more slowly than unbuffered ones.
Reverse-phase chromatography gives the clearest single view of related impurities and truncated sequences. Mass spectrometry then confirms that the main peak carries the expected mass. Neither test detects enantiomeric impurities, which require a separate chiral assay.
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.