1.
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
2.
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
3.
Google Books
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Books are provided either by publishers and authors, through the Google Books Partner Program, or by Googles library partners, through the Library Project. Additionally, Google has partnered with a number of publishers to digitize their archives. The Publisher Program was first known as Google Print when it was introduced at the Frankfurt Book Fair in October 2004, the Google Books Library Project, which scans works in the collections of library partners and adds them to the digital inventory, was announced in December 2004. But it has also criticized for potential copyright violations. As of October 2015, the number of scanned book titles was over 25 million, Google estimated in 2010 that there were about 130 million distinct titles in the world, and stated that it intended to scan all of them. Results from Google Books show up in both the universal Google Search as well as in the dedicated Google Books search website, if Google believes the book is still under copyright, a user sees snippets of text around the queried search terms. All instances of the terms in the book text appear with a yellow highlight. The four access levels used on Google Books are, Full view, Books in the domain are available for full view. In-print books acquired through the Partner Program are also available for full view if the publisher has given permission, usually, the publisher can set the percentage of the book available for preview. Users are restricted from copying, downloading or printing book previews, a watermark reading Copyrighted material appears at the bottom of pages. All books acquired through the Partner Program are available for preview and this could be because Google cannot identify the owner or the owner declined permission. If a search term appears many times in a book, Google displays no more than three snippets, thus preventing the user from viewing too much of the book. Also, Google does not display any snippets for certain reference books, such as dictionaries, Google maintains that no permission is required under copyright law to display the snippet view. No preview, Google also displays search results for books that have not been digitized, in effect, this is similar to an online library card catalog. Google also stated that it would not scan any in-copyright books between August and 1 November 2005, to provide the owners with the opportunity to decide which books to exclude from the Project. It can let Google scan the book under the Library Project and it can opt out of the Library Project, in which case Google will not scan the book. If the book has already been scanned, Google will reset its access level as No preview and this information is collated through automated methods, and sometimes data from third-party sources is used. This information provides an insight into the book, particularly useful when only a view is available
4.
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
5.
Mebeverine
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Mebeverine is a drug whose major therapeutic role is in the treatment of irritable bowel syndrome and the associated abdominal cramping. It works by relaxing the muscles in and around the gut and it is a musculotropic antispasmodic drug without anticholinergic side effects. The drug is indicated for treatment of gastrointestinal spasm secondary to organic disorder. It is also an inhibitor of calcium-depot replenishment, musculotropic compounds act directly on the gut muscles at the cellular level to relax them. This relieves painful muscle spasms of the gut, without affecting its normal motility, mebeverine is used to relieve symptoms of irritable bowel syndrome and related intestinal disorders that are the result of spasms in the intestinal muscles. These include colicky abdominal pain and cramps, diarrhoea alternating with constipation, most reactions consisted of urticaria or maculopapular rash, sometimes accompanied by fever, polyarthritis, thrombocytopenia or angioedema. Very rarely, people taking this medicine may develop allergic reactions, mebeverine passes into breast milk, but the amount is considered too small to be harmful to a nursing infant. Mebeverine is unlikely to affect the ability to operate machinery or to drive and it was first registered in 1965. Mebeverine is a drug and is available internationally under many brand names
6.
United States Adopted Name
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United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association, the United States Pharmacopeial Convention, and the American Pharmacists Association. In addition to drugs, the USAN Council names agents for gene therapy and cell therapy, contact lens polymers, surgical materials, diagnostics, carriers, the USAN Council began in June 1961 after the AMA and the USP jointly formed the AMA-USP Nomenclature Committee. In 1967, a representative from the Food and Drug Administration was appointed to serve on the USAN Council. The AMA Council on Drugs no longer exists as a separate entity, FDA now has a representative on the USAN Council, which has moved away from chemically derived names. Currently, the USAN Council has five members, one from each sponsoring organization, one from the FDA, one member is nominated to the USAN Council annually by each sponsoring organization, the FDA nominates one liaison member annually. The member-at-large is selected by the organizations from a list of candidates proposed by the AMA, APhA. The five nominees to the Council must be approved annually by the board of trustees of the three sponsoring organizations and this distinguishes them from the trademarked names that have been registered for private use. USANs assigned today reflect both present nomenclature practices and older methods used to name drug entities, early drug nomenclature was based on the chemical structure. As newer drugs became more complex and numerous, nonproprietary names based on chemistry became long and difficult to spell, pronounce. Additionally, chemically derived names provided little information to non-chemist health practitioners. Considering the needs of health led to a system in which USANs reflect relationships between new entities and older drugs, and avoid names that might suggest non-existent relationships. Current nomenclature practices involve the adoption of standardized syllables called stems that relate new chemical entities to existing drug families, stems may be prefixes, suffixes, or infixes in the nonproprietary name. Each stem can emphasize a specific chemical structure type, a pharmacologic property, the recommended list of USAN stems is updated regularly to keep pace to accommodate drugs with new chemical and pharmacologic properties. As a general rule, the application for a USAN should be forwarded to the USAN Council after the Investigational New Drug has been approved by the FDA and clinical trials have begun. Many drug manufacturers seeking a USAN are multinational companies with subsidiaries in various parts of the world or contractual agreements with drug firms outside the United States, assigning a USAN and standardizing names internationally can take anywhere from several months to a few years
7.
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
8.
Metamizole
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Metamizole, or dipyrone, is an ampyrone sulfonate analgesic, antispasmodic and antipyretic. Like paracetamol, it has minimal anti-inflammatory effects and it is most commonly given orally or parenterally to prevent and treat pain related to surgery or for the treatment of acute pain. It was first introduced into use in Germany in 1922 under the brandname Novalgin and for many years it was available over-the-counter in most countries. Although it is still available over-the-counter in some countries, it is now a drug in most developed countries, due to its potential for adverse events. Metamizole is marketed under trade names. It is primarily used for pain, acute injury, colic, cancer pain, other acute/chronic forms of pain. Metamizole has a potential of haematologic toxicity, but causes less kidney, cardiovascular, like NSAIDs, it can trigger bronchospasm or anaphylaxis, especially in those with asthma. The relative risk for agranulocytosis appears to vary according to the country of estimates on said rate. Oral anticoagulants, lithium, captopril, triamterene and antihypertensives may also interact with metamizole and it is considered fairly safe on overdose, but in these cases supportive measures are usually advised as well as measures to limit absorption and accelerate excretion. It is an acid and comes in calcium, sodium and magnesium salt forms. Recently, researchers uncovered another potential mechanism involving metamizole being a prodrug, in this proposal, not yet verified by other researchers, the metamizole itself breaks down into other chemicals that are the actual active agents. The result is a couple of cannabinoid and NSAID arachidonic acid conjugates of metamizoles breakdown products, despite this studies in animals have found that the first cannabinoid receptor is not involved in the analgesia induced by metamizole. Although it seems to inhibit fevers caused by prostaglandins, especially prostaglandin E2 and it appears to produce its therapeutic effects by means of its metabolites, especially N-methyl-4-aminoantipyrine and 4-aminoantipyrine. Ludwig Knorr was a student of Emil Fischer who won the Nobel Prize for his work on purines and sugars, which included the discovery of phenylhydrazine. Sales of that drug exploded, and in the 1890s chemists at Teerfarbenfabrik Meister, in 1893, a derivative of antipyrine, aminopyrine, was made by Friedrich Stolz at Hoechst. Metamizole was first marketed in Germany as Novalgin in 1922, metamizole is banned in several countries, available by prescription in others, and available over the counter in yet others. For example, approval was withdrawn in Sweden, the USA, metamizole is generic, and in countries where it is marketed, it is available under many brand names
9.
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
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