1.
Food and Drug Administration
–
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
2.
Massachusetts Institute of Technology
–
The Massachusetts Institute of Technology is a private research university in Cambridge, Massachusetts, often cited as one of the worlds most prestigious universities. Researchers worked on computers, radar, and inertial guidance during World War II, post-war defense research contributed to the rapid expansion of the faculty and campus under James Killian. The current 168-acre campus opened in 1916 and extends over 1 mile along the bank of the Charles River basin. The Institute is traditionally known for its research and education in the sciences and engineering, and more recently in biology, economics, linguistics. Air Force and 6 Fields Medalists have been affiliated with MIT, the school has a strong entrepreneurial culture, and the aggregated revenues of companies founded by MIT alumni would rank as the eleventh-largest economy in the world. In 1859, a proposal was submitted to the Massachusetts General Court to use newly filled lands in Back Bay, Boston for a Conservatory of Art and Science, but the proposal failed. A charter for the incorporation of the Massachusetts Institute of Technology, Rogers, a professor from the University of Virginia, wanted to establish an institution to address rapid scientific and technological advances. The Rogers Plan reflected the German research university model, emphasizing an independent faculty engaged in research, as well as instruction oriented around seminars, two days after the charter was issued, the first battle of the Civil War broke out. After a long delay through the war years, MITs first classes were held in the Mercantile Building in Boston in 1865, in 1863 under the same act, the Commonwealth of Massachusetts founded the Massachusetts Agricultural College, which developed as the University of Massachusetts Amherst. In 1866, the proceeds from sales went toward new buildings in the Back Bay. MIT was informally called Boston Tech, the institute adopted the European polytechnic university model and emphasized laboratory instruction from an early date. Despite chronic financial problems, the institute saw growth in the last two decades of the 19th century under President Francis Amasa Walker. Programs in electrical, chemical, marine, and sanitary engineering were introduced, new buildings were built, the curriculum drifted to a vocational emphasis, with less focus on theoretical science. The fledgling school still suffered from chronic financial shortages which diverted the attention of the MIT leadership, during these Boston Tech years, MIT faculty and alumni rebuffed Harvard University president Charles W. Eliots repeated attempts to merge MIT with Harvard Colleges Lawrence Scientific School. There would be at least six attempts to absorb MIT into Harvard, in its cramped Back Bay location, MIT could not afford to expand its overcrowded facilities, driving a desperate search for a new campus and funding. Eventually the MIT Corporation approved an agreement to merge with Harvard, over the vehement objections of MIT faculty, students. However, a 1917 decision by the Massachusetts Supreme Judicial Court effectively put an end to the merger scheme, the neoclassical New Technology campus was designed by William W. Bosworth and had been funded largely by anonymous donations from a mysterious Mr. Smith, starting in 1912. In January 1920, the donor was revealed to be the industrialist George Eastman of Rochester, New York, who had invented methods of production and processing
3.
Jmol
–
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
4.
Cathinone
–
Cathinone /ˈkæθᵻnoʊn/ is a monoamine alkaloid found in the shrub Catha edulis and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the main contributor to the stimulant effect of Catha edulis, Cathinone differs from many other amphetamines in that it has a ketone functional group. Other phenethylamines that share this structure include the stimulants methcathinone, MDPV, mephedrone, Khat has been cultivated in the Horn of Africa and Arabian Peninsula region of the world for thousands of years. It is most commonly chewed for the effect it produces. The active ingredient was first proposed in 1930, when cathine was identified as a predominant alkaloid in the plant. Cathine was thought to be the active ingredient in khat until the 1960s. In 1975, the United Nations Narcotic Laboratory analyzed khat leaves from Yemen, Kenya and Madagascar and found the presence of a different alkaloid, Cathinone is a similar molecule to cathine, but is much more abundant in younger plants. This finding caused scientists to speculate about whether cathinone was the active ingredient in khat. A study was conducted in 1994 to test the effects of cathinone, six volunteers who had never chewed khat were given an active khat sample and a cathinone-free placebo sample. The researchers analyzed the participants’ moods, activity levels and blood pressure before and this analysis showed that cathinone produced amphetamine-like symptoms, leading the researchers to confirm that cathinone, not cathine, is the active ingredient in khat leaves. Over 20 million people in the Arabian Peninsula and East Africa chew khat leaves daily and it is an important piece of the culture and economy in this region, especially in Ethiopia, where khat is said to have originated, Kenya, Djibouti, and Yemen. Men usually chew it during parties or other social gatherings while smoking cigarettes, farmers and other workers also use khat in the afternoon to reduce fatigue and hunger as the day goes on. It functions like the caffeine in a cup of coffee as an anti-fatigue drug. Students and drivers have known to use it to stay alert for longer periods of time. In order to produce its effects, khat leaves should be chewed fresh. The fresh leaves have a concentration of cathinone. Waiting too long after cultivation to chew the leaf will allow the cathinone to break down into its less potent form, because of the need for quick chewing, it is a habit that has historically been prevalent only where the plant grows. However, in the recent years with improvements in road and air transport, the cultivation of khat in Yemen is a highly profitable industry for farmers
5.
Pharmacokinetics
–
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.
Cathine
–
Cathine, also known as d-norpseudoephedrine and -norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant. Along with cathinone, it is naturally in Catha edulis. It has approximately 10-14% the potency of amphetamine, like amphetamines, cathinone, and ephedrine, cathine acts as a norepinephrine releasing agent. It also acts as a releasing agent to a lesser extent. Cathine is one of the four stereoisomers of phenylpropanolamine, the World Anti-Doping Agencys list of prohibited substances bars cathine in concentrations of over 5 micrograms per milliliter in urine. Cathine is a Schedule III drug under the Convention on Psychotropic Substances, in the United States, it is classified as a Schedule IV controlled substance. In Australia, Cathine is officially a schedule 4 drug but is not yet available or approved for any use, in Hong Kong, cathine is regulated under Schedule 1 of Hong Kongs Chapter 134 Dangerous Drugs Ordinance. Unlawful possession is punishable by fines and imprisonment. L-Norpseudoephedrine, an enantiomer Phenylpropanolamine Catha edulis Cathinone Methcathinone Ephedra sinica Ephedrine Pseudoephedrine Phenethylamine Amphetamine Methamphetamine
7.
Regulation of therapeutic goods
–
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
8.
Anti-obesity medication
–
Anti-obesity medication or weight loss drugs are all pharmacological agents that reduce or control weight. These drugs alter one of the processes of the human body, weight regulation, by altering either appetite. The main treatment modalities for overweight and obese individuals remain dieting, in the United States orlistat is currently approved by the FDA for long-term use. It reduces intestinal fat absorption by inhibiting pancreatic lipase, rimonabant, a second drug, works via a specific blockade of the endocannabinoid system. It has been developed from the knowledge that cannabis smokers often experience hunger and it had been approved in Europe for the treatment of obesity but has not received approval in the United States or Canada due to safety concerns. The European Medicines Agency in October 2008 recommended the suspension of the sale of rimonabant as the risks seem to be greater than the benefits, drugs blocking the cannabinoid receptors may be a future strategy for appetite suppression. Interference with the ability to absorb specific nutrients in food. For example, Orlistat blocks fat breakdown and thereby prevents fat absorption, the first described attempts at producing weight loss are those of Soranus of Ephesus, a Greek physician, in the second century AD. He prescribed elixirs of laxatives and purgatives, as well as heat, massage and this remained the mainstay of treatment for well over a thousand years. It was not until the 1920s and 1930s that new treatments began to appear, based on its effectiveness for hypothyroidism, thyroid hormone became a popular treatment for obesity in euthyroid people. It had a modest effect but produced the symptoms of hyperthyroidism as an effect, such as palpitations. 2, 4-Dinitrophenol was introduced in 1933, this worked by uncoupling the biological process of oxidative phosphorylation in mitochondria, the most significant side effect was a sensation of warmth, frequently with sweating. Overdose, although rare, lead to a rise in temperature and, ultimately. By the end of 1938 DNP had fallen out of use because the FDA had become empowered to put pressure on manufacturers, amphetamines became popular for weight loss during the late 1930s. They worked primarily by suppressing appetite, and had other effects such as increased alertness. Use of amphetamines increased over the subsequent decades, including Obetrol and this was a combination of multiple pills, all thought to help with weight loss, taken throughout the day. Typical regimens included stimulants, such as amphetamines, as well as thyroid hormone, diuretics, digitalis, laxatives, in 1967/1968 a number of deaths attributed to diet pills triggered a Senate investigation and the gradual implementation of greater restrictions on the market. Meanwhile, phentermine had been FDA approved in 1959 and fenfluramine in 1973, the two were no more popular than other drugs until in 1992 a researcher reported that when combined the two caused a 10% weight loss which was maintained for more than two years
9.
Serotonin
–
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
10.
Simplified molecular-input line-entry system
–
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
11.
Enantiomer
–
A single chiral atom or similar structural feature in a compound causes that compound to have two possible structures which are non-superposable, each a mirror image of the other. Each member of the pair is termed an enantiomorph, the property is termed enantiomerism. The presence of multiple features in a given compound increases the number of geometric forms possible. Enantiopure compounds refer to samples having, within the limits of detection and they are sometimes called optical isomers for this reason. Enantiomer members often have different chemical reactions with other enantiomer substances, since many biological molecules are enantiomers, there is sometimes a marked difference in the effects of two enantiomers on biological organisms. Owing to this discovery, drugs composed of one enantiomer can be developed to enhance the pharmacological efficacy. An example is eszopiclone, which is enantiopure and therefore administered in doses that are exactly 1/2 of the older, in the case of eszopiclone, the S enantiomer is responsible for all the desired effects, while the other enantiomer seems to be inactive. A dose of 2 mg of zopiclone must be administered to produce the therapeutic effect as 1 mg of eszopiclone. In chemical synthesis of enantiomeric substances, non-enantiomeric precursors inevitably produce racemic mixtures, in the absence of an effective enantiomeric environment, separation of a racemic mixture into its enantiomeric components is impossible. The R/S system is an important nomenclature system for denoting distinct enantiomers, another system is based on prefix notation for optical activity, - and - or d- and l-. The Latin for left and right is laevus and dexter, respectively, left and right have always had moral connotations, and the Latin words for these are sinister and rectus. The English word right is a cognate of rectus and this is the origin of the D, L and S, R notations, and the employment of prefixes levo- and dextro- in common names. Most compounds that one or more asymmetric carbon atoms show enantiomerism. There are a few compounds that do have asymmetric carbon atoms. An example of such an enantiomer is the sedative thalidomide, which was sold in a number of countries across the world from 1957 until 1961 and it was withdrawn from the market when it was found to cause of birth defects. One enantiomer caused the desirable effects, while the other, unavoidably present in equal quantities. The herbicide mecoprop is a mixture, with the --enantiomer possessing the herbicidal activity. Another example is the antidepressant drugs escitalopram and citalopram, citalopram is a racemate, escitalopram is a pure enantiomer
