1.
Drug nomenclature
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Drug nomenclature is the systematic naming of drugs, especially pharmaceutical drugs. Generic names for drugs are nowadays constructed out of affixes and stems that classify the drugs into different categories, a marketed drug might also have a company code or compound code. The chemical names are the names, based on the molecular structure of the drug. There are various systems of nomenclature and thus various chemical names for any one substance. The most important is the IUPAC name, chemical names are typically very long and too complex to be commonly used in referring to a drug. Sometimes, a company that is developing a drug might give the drug a company code, for example, CDP870 is UCB’s company code for Cimzia. Many of these codes, although not all, have prefixes that correspond to the company name, during development, the company will apply for regulatory approval of the drug by the relevant national regulatory agency, and it will apply for a generic name for that country. It will also apply for an International Nonproprietary Name through the World Health Organization, nowadays the national nonproprietary names are usually the same as the INN. The generic names usually indicate via their stems what drug class the drug belongs to, for example, one can tell that aciclovir is an antiviral drug because its name ends in the -vir suffix. Otherwise the 2 names are both given, joined by hyphens or slashes. For example, suspensions combining trimethoprim and sulfamethoxazole are called either trimethoprim/sulfamethoxazole or co-trimoxazole, similarly, co-codamol is codeine-acetaminophen, and co-triamterzide is triamterene-hydrochlorothiazide. The USP ceased maintaining PENs, but the similar co-prefixed BANs are still current, for drugs that make it all the way through development, testing, and regulatory acceptance, the pharmaceutical company then gives the drug a trade name. The term trade name is a term in the pharmaceutical industry for a brand name or trademark name. For example, Lipitor is Pfizers trade name for atorvastatin, a cholesterol-lowering medication, Drug names are often subject to legal regulation, including approval for new drugs and on packaging to establish clear rules about adulterants and fraudulent or misleading labelling. A national formulary is often designated to define drug names for regulatory purposes, unbiased mentions of a drug place the nonproprietary name first and follow it with the trade name in parentheses, if relevant. This pattern is important for the literature, where conflict of interest is disclosed or avoided. The authors reporting on a study are not endorsing any particular brand of drug and they will often state which brand was used, for methodologic validity, but they do so in a way that makes clear the absence of endorsement. For example, the 2015 American Society of Hematology publication policies say, Non-proprietary names should be used and he first letter of the name of a proprietary drug should be capitalized
2.
Drugs.com
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Drugs. com is an online pharmaceutical encyclopedia which provides drug information for consumers and healthcare professionals primarily in the USA. The domain Drugs. com was registered by Bonnie Neubeck in 1994. In 1999 at the height of the boom, Eric MacIver purchased an option to buy the domain from Neubeck. com. Venture Frogs sold the drugs. com domain name to an investor in June 2001. The Drugs. com website is owned and operated by the Drugsite Trust, the Drugsite Trust is a privately held Trust administered by two New Zealand pharmacists, Karen Ann and Phillip James Thornton The Drugs. com website was officially launched in September 2001. Stedmans, AHFS, Harvard Health Publications, Mayoclinic, North American Compendiums, in March 2008, Drugs. com announced the release of Mednotes —an online personal medication record application which connected to Google Health. In May 2010, U. S. FDA announced a collaboration with Drugs. com to distribute consumer health updates on the Drugs. com website, Drugs. com is certified by the TRUSTe online privacy certification program and the HONcode Health on the Net Foundation
3.
Regulation of therapeutic goods
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The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health, regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed, there is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Therapeutic goods in Australia are regulated by the Therapeutic Goods Administration, there are 5 main categories, Normal Medicines - Cough, cold and fever medicines, antiseptics, vitamins and others. Sold freely in pharmacies and some large supermarkets, red Stripe Medicines - These medicines are sold only with medical prescription. Antibiotics, Anti allergenics, Anti inflammatories, and other medicines, in Brazil, governmental control is loose on this type, it is not uncommon to buy this type of prescription medicine over the counter without a prescription. Red Stripe Psychoactive Medicines - These medicines are only with a Special Control white medical prescription with carbon copy. The original must be retained by the pharmacist after the sale, Drugs include anti-depressants, anti-convulsants, some sleep aids, anti-psychotics and other non-habit-inducing controlled medicines. Though some consider them habit inducing, anabolic steroids are also regulated under this category, black Stripe Medicines - These medicines are sold only with the Blue B Form medical prescription, which is valid for 30 days and must be retained by the pharmacist after the sale. Includes sedatives, some anorexic inducers and other habit-inducing controlled medicines, includes amphetamines and other stimulants, opioids and other strong habit-forming controlled medicines. In Canada, regulation of goods are governed by the Food and Drug Act. In addition, the Controlled Drugs and Substances Act requires additional regulatory requirements for controlled drugs, the regulation of drugs in Burma is governed by the Food and Drug Administration and Food and Drug Board of Authority. The regulation of drugs in China is governed by the China Food, Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency. The availability of drugs is regulated by classification by the MHRA as part of marketing authorisation of a product, Medicines in the Republic of Ireland are regulated according to the Misuse of Drugs Regulations 1988. Controlled drugs are divided into five categories based on their potential for misuse, cD1, cannabis, lysergamide, coca leaf, etc. Use prohibited except in limited circumstances where a license has been granted, CD2, amphetamine, methadone, morphine, fentanyl, oxycodone, tapentadol, etc
4.
Food and Drug Administration
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The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. As of 2017, 3/4th of the FDA budget is funded by the pharmaceutical companies due to the Prescription drug user fee act and these include regulating lasers, cellular phones, condoms and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice, the Commissioner reports to the Secretary of Health and Human Services. Dr. Robert M. Califf, MD is the current commissioner, who took over in February 2016 for Dr. Stephen Ostroff, the FDA has its headquarters in unincorporated White Oak, Maryland. The agency also has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, in 2008, the FDA began to post employees to foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom. The site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak, the first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. Only one original building from the facility was kept. All other buildings are new construction, the project is slated to be completed by 2017, assuming future Congressional funding While most of the Centers are located in the Washington, D. C. The Office of Regulatory Affairs is considered the eyes and ears of the agency, the Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. Districts are based roughly on the divisions of the federal court system. Each district comprises a main office and a number of Resident Posts. ORA also includes the Agencys network of laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, the Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, and dont focus on aspects of the regulated industries. In many cases, OCI pursues cases involving Title 18 violations, OCI Special Agents often come from other criminal investigations backgrounds, and work closely with the Federal Bureau of Investigation, Assistant Attorney General, and even Interpol. OCI receives cases from a variety of sources—including ORA, local agencies, OCI is a smaller branch, comprising about 200 agents nationwide. The FDA frequently works with federal agencies, including the Department of Agriculture, Drug Enforcement Administration, Customs and Border Protection. Often local and state government agencies also work with the FDA to provide regulatory inspections, the FDA regulates more than US$1 trillion worth of consumer goods, about 25% of consumer expenditures in the United States
5.
Pharmacokinetics
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Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as, pharmaceutical drugs, pesticides, food additives, cosmetic ingredients, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Pharmacokinetic properties of chemicals are affected by the route of administration and these may affect the absorption rate. Models have been developed to simplify conceptualization of the processes that take place in the interaction between an organism and a chemical substance. The various compartments that the model is divided into are commonly referred to as the ADME scheme, absorption - the process of a substance entering the blood circulation. Distribution - the dispersion or dissemination of substances throughout the fluids, metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion - the removal of the substances from the body, in rare cases, some drugs irreversibly accumulate in body tissue. The two phases of metabolism and excretion can also be grouped together under the title elimination, the study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. All these concepts can be represented through mathematical formulas that have a graphical representation. The model outputs for a drug can be used in industry or in the application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals, in practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph, compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model. The final outcome of the transformations that a drug undergoes in an organism, a number of functional models have been developed in order to simplify the study of pharmacokinetics. These models are based on a consideration of an organism as a number of related compartments, the simplest idea is to think of an organism as only one homogenous compartment. However, these models do not always reflect the real situation within an organism
6.
Bioavailability
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By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, its bioavailability generally decreases or may vary from patient to patient, Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration. Bioavailability is defined differently for drugs as opposed to dietary supplements primarily due to the method of administration and Food. Bioaccessibility is a related to bioavailability in the context of biodegradation. A molecule is said to be bioaccessible when is available to cross a cellular membrane from the environment. In pharmacology, bioavailability is a measurement of the rate and extent to which a drug reaches at the site of action and it is denoted by the letter f. Therefore, bioavailability for dietary supplements can be defined as the proportion of the administered substance capable of being absorbed, in both pharmacology and nutrition sciences, bioavailability is measured by calculating the area under curve of the drug concentration time profile. Bioavailability is commonly a factor in the production of crops. Toxic materials in soil, such as lead from paint may be rendered unavailable to animals ingesting contaminated soil by supplying phosphorus fertilizers in excess and it is the fraction of the drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug. The comparison must be normalized, consequently, the amount absorbed is corrected by dividing the corresponding dose administered. The absolute bioavailability is the area under curve non-intravenous divided by AUC intravenous. For example, the formula for calculating F for a drug administered by the route is given below. If we compare the two different dosage forms having same active ingredients and compare the two drug bioavailability is called comparative bioavailability, although knowing the true extent of systemic absorption is clearly useful, in practice it is not determined as frequently as one may think. The reason for this is that its assessment requires a reference, that is. These limitations may be overcome, however, by administering a low dose of an isotopically labelled drug concomitantly with a therapeutic non-labelled oral dose. This technique eliminates pharmacokinetic issues on non-equivalent clearance as well as enabling the intravenous dose to be administered with a minimum of toxicology, the technique was first applied using stable-isotopes such as 13C and mass-spectrometry to distinguish the isotopes by mass difference. More recently, 14C labelled drugs are administered intravenously and accelerator mass spectrometry used to measure the isotopically labelled drug along with mass spectrometry for the unlabelled drug, in all such cases, to conduct an absolute bioavailability study requires that the drug be given intravenously. Intravenous administration of a drug can provide valuable information on the fundamental pharmacokinetic parameters of volume of distribution
7.
Drug metabolism
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Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. These pathways are a form of biotransformation present in all groups of organisms. These reactions often act to detoxify poisonous compounds, the study of drug metabolism is called pharmacokinetics. The metabolism of drugs is an important aspect of pharmacology. For example, the rate of metabolism determines the duration and intensity of a drugs pharmacologic action, the enzymes of xenobiotic metabolism, particularly the glutathione S-transferases are also important in agriculture, since they may produce resistance to pesticides and herbicides. Drug metabolism is divided into three phases, in phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics. These modified compounds are conjugated to polar compounds in phase II reactions. These reactions are catalysed by enzymes such as glutathione S-transferases. Finally, in phase III, the conjugated xenobiotics may be processed, before being recognised by efflux transporters. Drug metabolism often converts lipophilic compounds into hydrophilic products that are readily excreted. The exact compounds an organism is exposed to will be unpredictable, and may differ widely over time. The solution that has evolved to address this problem is an elegant combination of physical barriers, all organisms use cell membranes as hydrophobic permeability barriers to control access to their internal environment. This selective uptake means that most hydrophilic molecules cannot enter cells, in contrast, the diffusion of hydrophobic compounds across these barriers cannot be controlled, and organisms, therefore, cannot exclude lipid-soluble xenobiotics using membrane barriers. However, the existence of a permeability barrier means that organisms were able to evolve detoxification systems that exploit the hydrophobicity common to membrane-permeable xenobiotics and these systems therefore solve the specificity problem by possessing such broad substrate specificities that they metabolise almost any non-polar compound. Useful metabolites are excluded since they are polar, and in general one or more charged groups. However, since these compounds are few in number, specific enzymes can recognize, the metabolism of xenobiotics is often divided into three phases, - modification, conjugation, and excretion. These reactions act in concert to detoxify xenobiotics and remove them from cells, in phase I, a variety of enzymes act to introduce reactive and polar groups into their substrates. One of the most common modifications is hydroxylation catalysed by the cytochrome P-450-dependent mixed-function oxidase system and these enzyme complexes act to incorporate an atom of oxygen into nonactivated hydrocarbons, which can result in either the introduction of hydroxyl groups or N-, O- and S-dealkylation of substrates
8.
Monoamine oxidase
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L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the membrane of mitochondria in most cell types in the body. The enzyme was discovered by Mary Bernheim in the liver and was named tyramine oxidase. They belong to the family of flavin-containing amine oxidoreductases. In humans there are two types of MAO, MAO-A and MAO-B, both are found in neurons and astroglia. Outside the central system, MAO-A is also found in the liver, pulmonary vascular endothelium, gastrointestinal tract. MAO-B is mostly found in blood platelets, MAO-A appears at roughly 80% of adulthood levels at birth, increasing very slightly after the first 4 years of life, while MAO-B is almost non-detectable in the infant brain. The cortex has relatively high levels of only MAO-A, with the exception of areas of the cingulate cortex, autopsied brains demonstrated the predicted increased concentration of MAO-A in regions dense in serotonergic neurotransmission, however MAO-B only correlated with norepinephrine. Monoamine oxidases catalyze the deamination of monoamines. Oxygen is used to remove a group from a molecule, resulting in the corresponding aldehyde. Monoamine oxidases contain the covalently bound cofactor FAD and are, thus, monoamine oxidase A and B share roughly 70% of their structure and both have substrate binding sites that are predominantly hydrophobic. Four main models have been proposed for the mechanism of electron transfer although there is insufficient evidence to support any of them and they are well known enzymes in pharmacology, since they are the substrate for the action of a number of monoamine oxidase inhibitor drugs. MAO-A is particularly important in the catabolism of monoamines ingested in food, both MAOs are also vital to the inactivation of monoaminergic neurotransmitters, for which they display different specificities. Serotonin, melatonin, norepinephrine, and epinephrine are mainly broken down by MAO-A, phenethylamine and benzylamine are mainly broken down by MAO-B. Both forms break down dopamine, tyramine, and tryptamine equally, excessive levels of catecholamines may lead to a hypertensive crisis, and excessive levels of serotonin may lead to serotonin syndrome. In fact, MAO-A inhibitors act as antidepressant and antianxiety agents, some research suggests that certain phenotypes of depression, such as those with anxiety, and atypical symptoms involving psychomotor retardation, weight gain and interpersonal sensitivity. However the findings related to this have not been consistent, mAOIs may be effective in treatment resistant depression, especially those that do not respond to tricyclic antidepressants. PET research has shown that MAO-B is also depleted by use of tobacco cigarettes
9.
Excretion
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Excretion is the process by which metabolic wastes and other non-useful materials are eliminated from an organism. In vertebrates this is carried out by the lungs, kidneys. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell, excretion is an essential process in all forms of life. For example, in urine is expelled through the urethra. In unicellular organisms, waste products are discharged directly through the surface of the cell, green plants produce carbon dioxide and water as respiratory products. In green plants, the carbon dioxide released during respiration gets utilized during photosynthesis, oxygen is a by product generated during photosynthesis, and exits through stomata, root cell walls, and other routes. Plants can get rid of water by transpiration and guttation. These latter processes do not need added energy, they act passively, however, during the pre-abscission phase, the metabolic levels of a leaf are high. Plants also excrete some waste substances into the soil around them, in animals, the main excretory products are carbon dioxide, ammonia, urea, uric acid, guanine and creatine. The liver and kidneys clear many substances from the blood, aquatic animals usually excrete ammonia directly into the external environment, as this compound has high solubility and there is ample water available for dilution. In terrestrial animals ammonia-like compounds are converted into other materials as there is less water in the environment. Birds excrete their nitrogenous wastes as uric acid in the form of a paste and this is metabolically more expensive, but allows more efficient water retention and it can be stored more easily in the egg. Many avian species, especially seabirds, can also excrete salt via specialized nasal salt glands, in insects, a system involving Malpighian tubules is utilized to excrete metabolic waste. Metabolic waste diffuses or is actively transported into the tubule, which transports the wastes to the intestines, the metabolic waste is then released from the body along with fecal matter. The excreted material may be called dejecta or ejecta, in pathology the word ejecta is more commonly used. UAlberta. ca, Animation of excretion Brian J Ford on leaf fall in Nature
10.
Urine
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Urine is a liquid by-product of metabolism in the bodies of many animals, including humans. It is expelled from the kidneys and flows through the ureters to the urinary bladder, cellular metabolism generates numerous by-products, many nitrogenous, that require clearance from the bloodstream. These by-products are eventually expelled from the body during urination, the method for excreting water-soluble chemicals from the body. These chemicals can be detected and analyzed by urinalysis, of the many such substances that exist, the three main nitrogenous wastes of the mammalian body are urea, uric acid, and creatinine. Animal urine forms part of the nitrogen cycle, in balanced ecosystems it fertilizes soil and plants, which in turn continue to support the animal population. Some animals use it to mark their territories, human urine and human feces are collectively referred to as human waste, as sewage, they require sewage treatment in places where population density is high. Livestock urine and feces similarly require proper management if the population density is high. Such management is part of ecological sanitation, most animals have excretory systems for elimination of soluble toxic wastes. In humans, soluble wastes are excreted primarily by the system and, to a lesser extent in terms of urea. The urinary system consists of the kidneys, ureters, urinary bladder, the system produces urine by a process of filtration, reabsorption, and tubular secretion. The kidneys extract the soluble wastes from the bloodstream, as well as water, sugars. The resulting urine contains high concentrations of urea and other substances, urine flows from the kidney through the ureter, bladder, and finally the urethra before passing from the body. Research looking at the duration of urination in a range of species found that 9 larger species urinated for 21 ±13 seconds irrespective of body size. Smaller species including rodents and bats cannot produce jets and instead urinate with a series of drops, producing too much or too little urine needs medical attention. Polyuria is a condition of excessive production of urine, oliguria when <400 mL are produced, about 91-96% of urine consists of water. Urine also contains an assortment of inorganic salts and organic compounds, including proteins, hormones, the total solids in urine are on average 59 g per person per day. Organic matter makes up between 65% and 85% of urine dry solids, with volatile solids comprising 75–85% of total solids, urea is the largest constituent of the solids, constituting more than 50% of the total. On an elemental level, human urine contains 6.87 g/L carbon,8.12 g/L nitrogen,8.25 g/L oxygen, the exact proportions vary with individuals and with factors such as diet and health
11.
Feces
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Feces or faeces are the solid or semisolid metabolic waste from an animals digestive tract, discharged through the anus or cloaca during a process called defecation. Urine and feces together are called excreta, collected feces has various uses, namely as fertilizer or soil conditioner in agriculture, as a fuel source, or for medicinal purposes. After an animal has digested eaten material, the remains of material are discharged from its body as waste. Although it is lower in energy than the food from which it is derived, feces may retain a large amount of energy and this means that of all food eaten, a significant amount of energy remains for the decomposers of ecosystems. Many organisms feed on feces, from bacteria to fungi to insects such as dung beetles, some may specialize in feces, while others may eat other foods as well. Feces serve not only as a food, but also as a supplement to the usual diet of some animals. Feces and urine, which reflect light, are important to raptors such as kestrels. Seeds also may be found in feces, animals who eat fruit are known as frugivores. An advantage for a plant in having fruit is that animals will eat the fruit and this mode of seed dispersal is highly successful, as seeds dispersed around the base of a plant are unlikely to succeed and often are subject to heavy predation. Provided the seed can withstand the pathway through the system, it is not only likely to be far away from the parent plant. This cycling of matter is known as the biogeochemical cycle, the distinctive odor of feces is due to bacterial action. Gut flora produce compounds such as indole, skatole, and thiols and these are the same compounds that are responsible for the odor of flatulence. Consumption of foods prepared with spices may result in the spices being undigested, the perceived bad odor of feces has been hypothesized to be a deterrent for humans, as consuming or touching it may result in sickness or infection. Human perception of the odor may be contrasted by an animals perception of it, for example. In humans and depending on the individual and the circumstances, defecation may occur daily, extensive hardening of the feces may cause prolonged interruption in the routine and is called constipation. Human fecal matter varies significantly in appearance, depending on diet, normally it is semisolid, with a mucus coating. The brown coloration comes from a combination of bile and bilirubin, in newborn babies, initially fecal matter is yellow-green after the meconium. This coloration comes from the presence of bile alone, throughout the life of an ordinary human, one may experience many types of feces
12.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
13.
Guide to Pharmacology
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The IUPHAR/BPS Guide to PHARMACOLOGY is an open-access website, acting as a portal to information on the biological targets of licensed drugs and other small molecules. The Guide to PHARMACOLOGY is developed as a joint venture between the International Union of Basic and Clinical Pharmacology and the British Pharmacological Society and this replaces and expands upon the original 2009 IUPHAR Database. The information featured includes pharmacological data, target and gene nomenclature, overviews and commentaries on each target family are included, with links to key references. The Guide to PHARMACOLOGY was initially made available online in December 2011 with additional material released in July 2012 and its network of over 700 specialist advisors contribute expertise and data. The current PI and Grant holder of the GtoPdb project is Prof. Jamie A. Davies, the development and release of the first version of the GtoPdb in 2012 was described in an editorial published in the British Journal of Pharmacology entitled Guide to Pharmacology. org- an update. The IUPHAR-DB is no longer being developed and all the contained within this site is now available through the Guide to PHARMACOLOGY. A complete list of all the approved drugs included on the website is available via the ligand list. The Guide to PHARMACOLOGY is being expanded to include information on targets and ligands. Search features on the website include quick and advanced search options, other features include Hot topic news items and a recent receptor-ligand pairing list. A hard copy summary of the database is published as The Concise Guide to Pharmacology 2015/2016 as a series of papers as a bi-annual supplement to the British Journal of Pharmacology. The Guide to PHARMACOLOGY includes links to other relevant resources via target, many of these resources maintain reciprocal links with the relevant Guide to PHARMACOLOGY pages. As of November 2015 the Wellcome Trust is supporting a new project to develop the Guide to Immumopharmacology, the latter continues to be supported by the British Pharmacological Society
14.
DrugBank
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The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets. As both a bioinformatics and a resource, DrugBank combines detailed drug data with comprehensive drug target information. Because of its scope, comprehensive referencing and unusually detailed data descriptions. As a result, links to DrugBank are maintained for nearly all drugs listed in Wikipedia, DrugBank is widely used by the drug industry, medicinal chemists, pharmacists, physicians, students and the general public. Its extensive drug and drug-target data has enabled the discovery and repurposing of a number of existing drugs to treat rare, the latest release of the database contains 8227 drug entries including 2003 FDA-approved small molecule drugs,221 FDA-approved biotech drugs,93 nutraceuticals and over 6000 experimental drugs. Additionally,4270 non-redundant protein sequences are linked to these drug entries, each DrugCard entry contains more than 200 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Four additional databases, HMDB, T3DB, SMPDB and FooDB are also part of a suite of metabolomic/cheminformatic databases. The first version of DrugBank was released in 2006 and this early release contained relatively modest information about 841 FDA-approved small molecule drugs and 113 biotech drugs. It also included information on 2133 drug targets, the second version of DrugBank was released in 2009. This greatly expanded and improved version of the database included 1344 approved small molecule drugs and 123 biotech drugs as well as 3037 unique drug targets. Version 2.0 also included, for the first time, withdrawn drugs and illicit drugs, version 3.0 was released in 2011. This version contained 1424 approved small molecule drugs and 132 biotech drugs as well as >4000 unique drug targets, version 3.0 also included drug transporter data, drug pathway data, drug pricing, patent and manufacturing data as well as data on >5000 experimental drugs. Version 4.0 was released in 2014 and this version included 1558 FDA-approved small molecule drugs,155 biotech drugs and 4200 unique drug targets. Version 4.0 also incorporated information on drug metabolites, drug taxonomy, drug spectra, drug binding constants. Table 1 provides a complete statistical summary of the history of DrugBank’s development. All data in DrugBank is non-proprietary or is derived from a non-proprietary source and it is freely accessible and available to anyone. In addition, nearly every item is fully traceable and explicitly referenced to the original source. DrugBank data is available through a web interface and downloads
15.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
16.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets
17.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU. This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can then move to another list
18.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
19.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
20.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
21.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
22.
Triptan
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Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first introduced in the 1990s, while effective at treating individual headaches, they do not provide preventative treatment and are not considered a cure. They are not effective for the treatment of tension headache or other kinds of pain, the drugs of this class act as agonists for serotonin 5-HT1B and 5-HT1D receptors at blood vessels and nerve endings in the brain. The first clinically available triptan was sumatriptan, which has been marketed since 1991, triptans are used for the treatment of severe migraine attacks or those that do not respond to NSAIDs or other over-the-counter drugs. Triptans are a mid-line treatment suitable for many migraineurs with typical attacks and they may not work for atypical or unusually severe migraine attacks, transformed migraine, or status migrainosus. Triptans are highly effective, reducing the symptoms or aborting the attack within 30 to 90 minutes in 70–80% of patients, a test measuring a persons skin sensitivity during a migraine may indicate whether the individual will respond to treatment with triptans. Triptans are most effective in those with no skin sensitivity, with skin sensitivity, oral rizatriptan and nasal zolmitriptan are the most used triptans for migraines in children. Triptans are effective for the treatment of cluster headache and this has been demonstrated for subcutaneous sumatriptan and intranasal zolmitriptan, the former of which is more effective according to a 2013 Cochrane review. Tablets were not considered appropriate in this review, a single randomized controlled trial found that sumatriptan may be able to prevent altitude sickness. All marketed triptans are available in form, some in form of sublingual tablets. Sumatriptan and zolmitriptan are also available as nasal sprays, all triptans are contraindicated in patients with cardiovascular diseases. Most triptans are contraindicated during pregnancy and breastfeeding and for patients younger than 18. Combination with monoamine oxidase inhibitors is contraindicated for sumatriptan, zolmitriptan and rizatriptan, triptans have few side effects if used in correct dosage and frequency. The most common effect is recurrence of migraine. A systematic review found that rizatriptan 10 mg was the only triptan with a rate greater than that of placebo. There is a risk of coronary spasm in patients with established heart disease. There is the potential for life-threatening serotonin syndrome in patients taking triptans, combining triptans with ergot alkaloids is contraindicated because of the danger of coronary spasms. Pharmacokinetic interactions are different for the substances, for most triptans
23.
Indole
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Indole is an aromatic heterocyclic organic compound with formula C8H7N. It has a structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is widely distributed in the environment and can be produced by a variety of bacteria. As an intercellular signal molecule, indole regulates various aspects of physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation. The amino acid tryptophan is a derivative and the precursor of the neurotransmitter serotonin. Indole is a solid at room temperature, Indole can be produced by bacteria as a degradation product of the amino acid tryptophan. It occurs naturally in feces and has an intense fecal odor. At very low concentrations, however, it has a flowery smell and it also occurs in coal tar. The corresponding substituent is called indolyl, Indole undergoes electrophilic substitution, mainly at position 3. Substituted indoles are structural elements of the tryptophan-derived tryptamine alkaloids like the neurotransmitter serotonin, other indolic compounds include the plant hormone auxin, tryptophol, the anti-inflammatory drug indomethacin, the betablocker pindolol, and the naturally occurring hallucinogen dimethyltryptamine. The name indole is a portmanteau of the indigo and oleum. Indole chemistry began to develop with the study of the dye indigo, indigo can be converted to isatin and then to oxindole. Then, in 1866, Adolf von Baeyer reduced oxindole to indole using zinc dust, in 1869, he proposed a formula for indole. Certain indole derivatives were important dyestuffs until the end of the 19th century, in the 1930s, interest in indole intensified when it became known that the indole substituent is present in many important alkaloids, and it remains an active area of research today. It condenses with serine by Michael addition of indole to PLP-aminoacrylate, as an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence. The amino acid tryptophan is a derivative and the precursor of the neurotransmitter serotonin. Indole is a constituent of coal tar, and the 220–260 °C distillation fraction is the main industrial source of the material. Indole and its derivatives can also be synthesized by a variety of methods, the main industrial routes start from aniline via vapor-phase reaction with ethylene glycol in the presence of catalysts, In general, reactions are conducted between 200 and 500 °C
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Sulfur
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Sulfur or sulphur is a chemical element with symbol S and atomic number 16. It is abundant, multivalent, and nonmetallic, under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a yellow crystalline solid at room temperature. Chemically, sulfur reacts with all elements except for gold, platinum, iridium, tellurium, though sometimes found in pure, native form, sulfur usually occurs as sulfide and sulfate minerals. Being abundant in native form, sulfur was known in ancient times, being mentioned for its uses in ancient India, ancient Greece, China, in the Bible, sulfur is called brimstone. Today, almost all elemental sulfur is produced as a byproduct of removing sulfur-containing contaminants from natural gas, the greatest commercial use of the element is the production of sulfuric acid for sulfate and phosphate fertilizers, and other chemical processes. The element sulfur is used in matches, insecticides, and fungicides, many sulfur compounds are odoriferous, and the smells of odorized natural gas, skunk scent, grapefruit, and garlic are due to organosulfur compounds. Hydrogen sulfide gives the characteristic odor to rotting eggs and other biological processes, sulfur is an essential element for all life, but almost always in the form of organosulfur compounds or metal sulfides. Three amino acids and two vitamins are organosulfur compounds, many cofactors also contain sulfur including glutathione and thioredoxin and iron–sulfur proteins. Disulfides, S–S bonds, confer mechanical strength and insolubility of the keratin, found in outer skin, hair. Sulfur is one of the chemical elements needed for biochemical functioning and is an elemental macronutrient for all organisms. Sulfur is derived from the Latin word sulpur, which was Hellenized to sulphur, the spelling sulfur appears toward the end of the Classical period. In 12th-century Anglo-French, it was sulfre, in the 14th century the Latin ph was restored, for sulphre, the parallel f~ph spellings continued in Britain until the 19th century, when the word was standardized as sulphur. Sulfur was the form chosen in the United States, whereas Canada uses both, the IUPAC adopted the spelling sulfur in 1990, as did the Nomenclature Committee of the Royal Society of Chemistry in 1992, restoring the spelling sulfur to Britain. Sulfur forms polyatomic molecules with different chemical formulas, the best-known allotrope being octasulfur, cyclo-S8. The point group of cyclo-S8 is D4d and its dipole moment is 0 D. Octasulfur is a soft, bright-yellow solid that is odorless and it melts at 115.21 °C, boils at 444.6 °C and sublimes easily. At 95.2 °C, below its melting temperature, cyclo-octasulfur changes from α-octasulfur to the β-polymorph, the structure of the S8 ring is virtually unchanged by this phase change, which affects the intermolecular interactions. At higher temperatures, the viscosity decreases as depolymerization occurs, molten sulfur assumes a dark red color above 200 °C
25.
Hemoglobin
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Hemoglobin in the blood carries oxygen from the respiratory organs to the rest of the body. There it releases the oxygen to permit aerobic respiration to provide energy to power the functions of the organism in the process called metabolism, in mammals, the protein makes up about 96% of the red blood cells dry content, and around 35% of the total content. Hemoglobin has a capacity of 1.34 mL O2 per gram. The mammalian hemoglobin molecule can bind up to four oxygen molecules, Hemoglobin is involved in the transport of other gases, It carries some of the bodys respiratory carbon dioxide as carbaminohemoglobin, in which CO2 is bound to the globin protein. The molecule also carries the important regulatory molecule nitric oxide bound to a globin protein thiol group, Hemoglobin is also found outside red blood cells and their progenitor lines. Other cells that contain hemoglobin include the A9 dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, in these tissues, hemoglobin has a non-oxygen-carrying function as an antioxidant and a regulator of iron metabolism. Hemoglobin and hemoglobin-like molecules are found in many invertebrates, fungi. In these organisms, hemoglobins may carry oxygen, or they may act to transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. In 1825 J. F. Engelhard discovered that the ratio of Fe to protein is identical in the hemoglobins of several species, from the known atomic mass of iron he calculated the molecular mass of hemoglobin to n ×16000, the first determination of a proteins molecular mass. This hasty conclusion drew a lot of ridicule at the time from scientists who could not believe that any molecule could be that big, gilbert Smithson Adair confirmed Engelhards results in 1925 by measuring the osmotic pressure of hemoglobin solutions. The oxygen-carrying protein hemoglobin was discovered by Hünefeld in 1840, hemoglobins reversible oxygenation was described a few years later by Felix Hoppe-Seyler. In 1959, Max Perutz determined the structure of myoglobin by X-ray crystallography. This work resulted in his sharing with John Kendrew the 1962 Nobel Prize in Chemistry, the role of hemoglobin in the blood was elucidated by French physiologist Claude Bernard. The name hemoglobin is derived from the heme and globin. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces, the most common type of hemoglobin in mammals contains four such subunits. Hemoglobin consists of subunits, and these proteins, in turn, are folded chains of a large number of different amino acids called polypeptides. The amino acid sequence of any polypeptide created by a cell is in turn determined by the stretches of DNA called genes, in all proteins, it is the amino acid sequence that determines the proteins chemical properties and function. There is more than one gene, in humans, hemoglobin A is coded for by the genes, HBA1, HBA2
26.
Serotonin
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Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is found in the gastrointestinal tract, blood platelets. It is popularly thought to be a contributor to feelings of well-being, approximately 90% of the human bodys total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements. The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions and these include the regulation of mood, appetite, and sleep. Serotonin also has some functions, including memory and learning. Modulation of serotonin at synapses is thought to be an action of several classes of pharmacological antidepressants. Serotonin secreted from the cells eventually finds its way out of tissues into the blood. There, it is taken up by blood platelets, which store it. When the platelets bind to a clot, they release serotonin, Serotonin is also a growth factor for some types of cells, which may give it a role in wound healing. Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver, metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. This is followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the acetic acid derivative. The latter is then excreted by the kidneys, in addition to animals, serotonin is found in fungi and plants. Serotonins presence in insect venoms and plant spines serves to cause pain, Serotonin is produced by pathogenic amoebae, and its effect on the gut causes diarrhea. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds, Serotonin is a neurotransmitter and is found in all bilateral animals, where it mediates gut movements and the animals perceptions of resource availability. In less complex animals, such as invertebrates, resources simply mean food availability. In more complex animals, such as arthropods and vertebrates, resources also can mean social dominance, in response to the perceived abundance or scarcity of resources, an animals growth, reproduction or mood may be elevated or lowered. This may somewhat depend on how much serotonin the organism has at its disposal, except for the 5-HT3 receptor, a ligand-gated ion channel, all other 5-HT receptors are G-protein-coupled receptors that activate an intracellular second messenger cascade. Serotonergic action is terminated primarily via uptake of 5-HT from the synapse and this is accomplished through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron
27.
5-HT receptor
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They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the serotonin, which acts as their natural ligand. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. Serotonin receptors are found in almost all animals and humans and are known to regulate longevity and behavioral aging in the primitive nematode. In 2014 a novel 5-HT receptor was described that was isolated from the white butterfly, Pieris rapae. It shares relatively low similarity to the known 5-HT receptor classes and does not occur in mammals, the 7 general serotonin receptor classes include a total of 14 known serotonin receptors. Very nonselective agonists of 5-HT receptor subtypes include ergotamine, which activates 5-HT1A, 5-HT1D, 5-HT1B, D2, LSD is a 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist. Serotonin Receptors at the US National Library of Medicine Medical Subject Headings 5-Hydroxytryptamine Receptors, IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology, activation of G protein-coupled receptors entails cysteine modulation of agonist binding. Paterson LM, Kornum BR, Nutt DJ, Pike VW, 5-HT radioligands for human brain imaging with PET and SPECT
. PMID 10073743.
