European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards 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 used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification 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 and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough 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 import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, 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 identified in the EU as being of 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 move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
The 5-HT3 receptor belongs to the Cys-loop superfamily of ligand-gated ion channels and therefore differs structurally and functionally from all other 5-HT receptors receptors which are G protein-coupled receptors. This ion channel is cation-selective and mediates neuronal depolarization and excitation within the central and peripheral nervous systems; as with other ligand gated ion channels, the 5-HT3 receptor consists of five subunits arranged around a central ion conducting pore, permeable to sodium and calcium ions. Binding of the neurotransmitter 5-hydroxytryptamine to the 5-HT3 receptor opens the channel, which, in turn, leads to an excitatory response in neurons; the activating, inward current is predominantly carried by sodium and potassium ions. 5-HT3 receptors have a negligible permeability to anions. They are most related by homology to the nicotinic acetylcholine receptor; the 5-HT3 receptor differs markedly in structure and mechanism from the other 5-HT receptor subtypes, which are all G-protein-coupled.
A functional channel may be composed of five identical 5-HT3A subunits or a mixture of 5-HT3A and one of the other four 5-HT3B, 5-HT3C, 5-HT3D, or 5-HT3E subunits. It appears. All other subunit subtypes must heteropentamerize with 5-HT3A subunits to form functional channels. Additionally, there has not been any pharmacological difference found between the heteromeric 5-HT3AC, 5-HT3AD, 5-HT3AE, the homomeric 5-HT3A receptor. N-terminal glycosylation of receptor subunits is critical for subunit assembly and plasma membrane trafficking; the subunits surround a central ion channel in a pseudo-symmetric manner. Each subunit comprises an extracellular N-terminal domain which comprises the orthosteric ligand-binding site. Whereas extracellular domain is the site of action of agonists and competitive antagonists, the transmembrane domain contains the central ion pore, receptor gate, principle selectivity filter that allows ions to cross the cell membrane; the 5-HT3 receptor gene is located on human chromosomal region 11q23.1-q23.2.
It is similar in structure to the mouse gene, spread over ~ 13 kb. Four of its introns are in the same position as the introns in the homologous α7-acetylcholine receptor gene proving their evolutionary relationship. Additional genes that code for the subunits of the 5-HT3 receptor have been identified. HTR3A and HTR3B for the 5-HT3A and 5-HT3B subunits and in addition HTR3C, HTR3D and HTR3E genes encoding 5-HT3C, 5-HT3D and 5-HT3E subunits. HTR3C and HTR3E do not seem to form functional homomeric channels, but when co-expressed with HTR3A they form heteromeric complex with decreased or increased 5-HT efficacies; the pathophysiological role for these additional subunits has yet to be identified. Expression; the 5-HT3C, 5-HT3D and 5-HT3E genes tend to show peripherally restricted pattern of expression, with high levels in the gut. In human duodenum and stomach, for example, 5-HT3C and 5-HT3E mRNA might be greater than for 5-HT3A and 5-HT3B. Polymorphism. In patients treated with chemotherapeutic drugs, certain polymorphism of the HTR3B gene could predict successful antiemetic treatment.
This could indicate that the 5-HTR3B receptor subunit could be used as biomarker of antiemetic drug efficacy. The 5-HT3 receptor is expressed throughout the central and peripheral nervous systems and mediates a variety of physiological functions. On a cellular level, it has been shown that postsynaptic 5-HT3 receptors mediate fast excitatory synaptic transmission in rat neocortical interneurons and hippocampus, in ferret visual cortex. 5-HT3 receptors are present on presynaptic nerve terminals. There is some evidence for a role in modulation of neurotransmitter release, but evidence is inconclusive; when the receptor is activated to open the ion channel by agonists, the following effects are observed: CNS: nausea and vomiting center in brain stem, seizure propensity, pro-nociception PNS: neuronal excitation, emesis Agonists for the receptor include: Cereulide 2-methyl-5-HT Alpha-Methyltryptamine Bufotenin Chlorophenylbiguanide Ethanol Ibogaine Phenylbiguanide Quipazine RS-56812: Potent and selective 5-HT3 partial agonist, 1000x selectivity over other serotonin receptors SR-57227 Varenicline YM-31636 Antagonists for the receptor include: Antiemetics AS-8112 Granisetron Ondansetron Tropisetron Gastroprokinetics Alosetron Batanopride Metoclopramide Renzapride Zacopride M1, the major active metabolite of mosapride Antidepressants Mianserin Mirtazapine Vortioxetine Antipsychotics Clozapine Olanzapine Quetiapine Antimalarials Quinine Chloroquine Mefloquine Others 3-Tropanyl indole-3-carboxylate Lamotrigine Memantine Menthol Thujone These agents are not agonists at the receptor, but increase the affinity or efficacy of the receptors for an agonist: Indole Derivatives 5-chloroindole Small Organic Anaesthetics Ethanol Chloroform Halothane Isoflurane Identification of the 5-HT3 receptor did not take place until 1986 because of a lack of selective pharmacological tool.
However, with the discovery that the 5-HT3 receptor plays a prominent role in chemotherapy- and radiotherapy-induced vomiting, the conc
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both inhibitory neurotransmission; the serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand. The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, epinephrine / norepinephrine, acetylcholine, as well as many hormones, including oxytocin, vasopressin, cortisol and substance P, among others; the serotonin receptors influence various biological and neurological processes such as aggression, appetite, learning, mood, nausea and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and recreational drugs, including many antidepressants, anorectics, gastroprokinetic agents, antimigraine agents and entactogens. Serotonin receptors are found in all animals and are known to regulate longevity and behavioral aging in the primitive nematode, Caenorhabditis elegans.
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors are found in the central and peripheral nervous systems. They can be divided into 7 families of G protein-coupled receptors except for the 5-HT3 receptor, a ligand-gated ion channel, which activate an intracellular second messenger cascade to produce an excitatory or inhibitory response. In 2014, a novel 5-HT receptor was isolated from the small white butterfly, Pieris rapae, named pr5-HT8, it does not occur in mammals and shares low similarity to the known 5-HT receptor classes. The 7 general serotonin receptor classes include a total of 14 known serotonin receptors; the specific types have been characterized as follows: Note that there is no 5-HT1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT2 family of receptors and was redesignated as the 5-HT2C receptor. Nonselective agonists of 5-HT receptor subtypes include ergotamine, which activates 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.
LSD is a 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist. The genes coding for serotonin receptors are expressed across the mammalian brain. Genes coding for different receptors types follow different developmental curves. There is a developmental increase of HTR5A expression in several subregions of the human cortex, paralleled by a decreased expression of HTR1A from the embryonic period to the post-natal one. A number of receptors were classed as "5-HT1-like" - by 1998 it was being argued that, since these receptors were "a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7" receptors the classification was redundant. 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. Rubenstein LA, Lanzara RG. "Activation of G protein-coupled receptors entails cysteine modulation of agonist binding". Cogprints. Retrieved 2008-04-11. Paterson LM, Kornum BR, Nutt DJ, Pike VW, Knudsen GM.
"5-HT radioligands for human brain imaging with PET and SPECT". Med Res Rev. 33: 54–111. Doi:10.1002/med.20245. PMC 4188513. PMID 21674551
Piperazine is an organic compound that consists of a six-membered ring containing two nitrogen atoms at opposite positions in the ring. Piperazine exists as small alkaline deliquescent crystals with a saline taste; the piperazines are a broad class of chemical compounds, many with important pharmacological properties, which contain a core piperazine functional group. Piperazines were named because of their chemical similarity with piperidine, part of the structure of piperine in the black pepper plant, it is important to note, that piperazines are not derived from plants in the Piper genus. Piperazine is soluble in water and ethylene glycol, but insoluble in diethyl ether, it is a weak base with two pKbs of 5.35 and 9.73 at 25 °C.. Piperazine absorbs water and carbon dioxide from the air. Although many piperazine derivatives occur piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.
A form in which piperazine is available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Two common salts in the form of which piperazine is prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7, the adipate, C4H10N2. C6H10O4. Piperazine is formed as a co-product in the ammoniation of ethanolamine; these are the only routes to the chemical used commercially. The piperazine is separated from the product stream, which contains ethylenediamine, diethylenetriamine, other related linear and cyclic chemicals of this type. Piperazine was first introduced as an anthelmintic in 1953. A large number of piperazine compounds have anthelmintic action, their mode of action is by paralysing parasites, which allows the host body to remove or expel the invading organism. The neuromuscular effects are thought to be caused by blocking acetylcholine at the myoneural junction; this action is mediated by its agonist effects upon the inhibitory GABA receptor.
Its selectivity for helminths is because vertebrates only use GABA in the CNS and the GABA receptor of helminths is of a different isoform from that of vertebrates. Piperazine hydrate, piperazine adipate and piperazine citrate are the most common anthelmintic piperazine compounds; these drugs are referred to as "piperazine" which may cause confusion between the specific anthelmintic drugs, the entire class of piperazine-containing compounds, the compound itself. Diethylcarbamazine, a derivative of piperazine, is used to treat some types of filariasis. Piperazines are used in the manufacture of plastics, pesticides, brake fluid and other industrial materials. Piperazines BZP and TFMPP were common adulterants in the club and rave scene being passed off as MDMA, although they do not share many similarities in their effects. Piperazine is a fluid used for CO2 and H2S scrubbing in association with methyl diethanolamine. Amine blends that are activated by concentrated piperazine are used extensively in commercial CO2 removal for carbon capture and storage because piperazine advantageously allows for protection from significant thermal and oxidative degradation at typical coal flue gas conditions.
The thermal degradation rates for methyl diethanolamine and piperazine are negligible, PZ, unlike other metals, protect MDEA from oxidative degradation. This increased stability of the MDEA/PZ solvent blend over MDEA and other amine solvents provides for greater capacity for and requires less work to capture a given amount of CO2. Piperazine's solubility is low, so it is used in small amounts to supplement another amine solvent. One or more of piperazine's performance advantages are compromised in practice due to its low concentration. For example, a 5 m PZ/5 m MDEA blend yields an 11% larger difference in CO2 concentration than 8 m PZ between the lean and rich amine solvent streams, or in other words, more CO2 is removed from the sour gas stream per unit mass of solvent, an 100% larger concentration difference than 7 m MEA. Given that typical amine-based absorption processes run at temperatures from 45 °C to 55 °C, the capabilities of piperazine are well within the bounds of and thus favored for carbon capture.
Piperazine can be thermally regenerated through multi-stage flash distillation and other methods after being used in operating temperatures up to 150 °C and recycled back into the absorption process, providing for higher overall energy performance in amine gas treating processes. The advantages to using concentrated piperazine as an additive had been confirmed through, for example, three pilot plants in Australia that are operated by CSIRO; this program was launched to explore remedies to the high costs of post-combustion carbon capture, the results were positive. Using CPZ, more reactive and thermally stable than standard MEA solutions and compression costs were lowered through size reductions in absorber columns and solvent regeneration at higher temperatures; the amine groups on piperazine react with
A drug is any substance that, when inhaled, smoked, absorbed via a patch on the skin, or dissolved under the tongue causes a physiological change in the body. In pharmacology, a drug is a chemical substance of known structure, other than a nutrient of an essential dietary ingredient, when administered to a living organism, produces a biological effect. A pharmaceutical drug called a medication or medicine, is a chemical substance used to treat, prevent, or diagnose a disease or to promote well-being. Traditionally drugs were obtained through extraction from medicinal plants, but more also by organic synthesis. Pharmaceutical drugs may be used for a limited duration, or on a regular basis for chronic disorders. Pharmaceutical drugs are classified into drug classes—groups of related drugs that have similar chemical structures, the same mechanism of action, a related mode of action, that are used to treat the same disease; the Anatomical Therapeutic Chemical Classification System, the most used drug classification system, assigns drugs a unique ATC code, an alphanumeric code that assigns it to specific drug classes within the ATC system.
Another major classification system is the Biopharmaceutics Classification System. This classifies drugs according to their permeability or absorption properties. Psychoactive drugs are chemical substances that affect the function of the central nervous system, altering perception, mood or consciousness, they include alcohol, a depressant, the stimulants nicotine and caffeine. These three are the most consumed psychoactive drugs worldwide and are considered recreational drugs since they are used for pleasure rather than medicinal purposes. Other recreational drugs include hallucinogens and amphetamines and some of these are used in spiritual or religious settings; some drugs can cause addiction and all drugs can have side effects. Excessive use of stimulants can promote stimulant psychosis. Many recreational drugs are illicit and international treaties such as the Single Convention on Narcotic Drugs exist for the purpose of their prohibition. In English, the noun "drug" is thought to originate from Old French "drogue" deriving into "droge-vate" from Middle Dutch meaning "dry barrels", referring to medicinal plants preserved in them.
The transitive verb "to drug" arose and invokes the psychoactive rather than medicinal properties of a substance. A medication or medicine is a drug taken to cure or ameliorate any symptoms of an illness or medical condition; the use may be as preventive medicine that has future benefits but does not treat any existing or pre-existing diseases or symptoms. Dispensing of medication is regulated by governments into three categories—over-the-counter medications, which are available in pharmacies and supermarkets without special restrictions. In the United Kingdom, behind-the-counter medicines are called pharmacy medicines which can only be sold in registered pharmacies, by or under the supervision of a pharmacist; these medications are designated by the letter P on the label. The range of medicines available without a prescription varies from country to country. Medications are produced by pharmaceutical companies and are patented to give the developer exclusive rights to produce them; those that are not patented are called generic drugs since they can be produced by other companies without restrictions or licenses from the patent holder.
Pharmaceutical drugs are categorised into drug classes. A group of drugs will share a similar chemical structure, or have the same mechanism of action, the same related mode of action or target the same illness or related illnesses; the Anatomical Therapeutic Chemical Classification System, the most used drug classification system, assigns drugs a unique ATC code, an alphanumeric code that assigns it to specific drug classes within the ATC system. Another major classification system is the Biopharmaceutics Classification System; this groups drugs according to their permeability or absorption properties. Some religions ethnic religions are based on the use of certain drugs, known as entheogens, which are hallucinogens,—psychedelics, dissociatives, or deliriants; some drugs used as entheogens include kava which can act as a stimulant, a sedative, a euphoriant and an anesthetic. The roots of the kava plant are used to produce a drink, consumed throughout the cultures of the Pacific Ocean; some shamans from different cultures use entheogens, defined as "generating the divine within" to achieve religious ecstasy.
Amazonian shamans use ayahuasca a hallucinogenic brew for this purpose. Mazatec shamans have a long and continuous tradition of religious use of Salvia divinorum a psychoactive plant, its use is to facilitate visionary states of consciousness during spiritual healing sessions. Silene undulata is used as an entheogen, its root is traditionally used to induce vivid lucid dreams during the initiation process of shamans, classifying it a occurring oneirogen similar to the more well-known dream herb Calea ternifolia. Peyote a small spineless cactus has been a
The scientific method is an empirical method of acquiring knowledge that has characterized the development of science since at least the 17th century. It involves careful observation, applying rigorous skepticism about what is observed, given that cognitive assumptions can distort how one interprets the observation, it involves formulating hypotheses, via induction, based on such observations. These are principles of the scientific method, as distinguished from a definitive series of steps applicable to all scientific enterprises. Though diverse models for the scientific method are available, there is in general a continuous process that includes observations about the natural world. People are inquisitive, so they come up with questions about things they see or hear, they develop ideas or hypotheses about why things are the way they are; the best hypotheses lead to predictions. The most conclusive testing of hypotheses comes from reasoning based on controlled experimental data. Depending on how well additional tests match the predictions, the original hypothesis may require refinement, expansion or rejection.
If a particular hypothesis becomes well supported, a general theory may be developed. Although procedures vary from one field of inquiry to another, they are the same from one to another; the process of the scientific method involves making conjectures, deriving predictions from them as logical consequences, carrying out experiments or empirical observations based on those predictions. A hypothesis is a conjecture, based on knowledge obtained while seeking answers to the question; the hypothesis might be specific, or it might be broad. Scientists test hypotheses by conducting experiments or studies. A scientific hypothesis must be falsifiable, implying that it is possible to identify a possible outcome of an experiment or observation that conflicts with predictions deduced from the hypothesis; the purpose of an experiment is to determine whether observations agree with or conflict with the predictions derived from a hypothesis. Experiments can take place anywhere from a garage to CERN's Large Hadron Collider.
There are difficulties in a formulaic statement of method, however. Though the scientific method is presented as a fixed sequence of steps, it represents rather a set of general principles. Not all steps take place in every scientific inquiry, they are not always in the same order; some philosophers and scientists have argued. Robert Nola and Howard Sankey remark that "For some, the whole idea of a theory of scientific method is yester-year's debate, the continuation of which can be summed up as yet more of the proverbial deceased equine castigation. We beg to differ." Important debates in the history of science concern rationalism as advocated by René Descartes. The term "scientific method" emerged in the 19th century, when a significant institutional development of science was taking place and terminologies establishing clear boundaries between science and non-science, such as "scientist" and "pseudoscience", appeared. Throughout the 1830s and 1850s, by which time Baconianism was popular, naturalists like William Whewell, John Herschel, John Stuart Mill engaged in debates over "induction" and "facts" and were focused on how to generate knowledge.
In the late 19th and early 20th centuries, a debate over realism vs. antirealism was conducted as powerful scientific theories extended beyond the realm of the observable. The term "scientific method" came into popular use in the twentieth century, popping up in dictionaries and science textbooks, although there was little scientific consensus over its meaning. Although there was a growth through the middle of the twentieth century, by the end of that century numerous influential philosophers of science like Thomas Kuhn and Paul Feyerabend had questioned the universality of the "scientific method" and in doing so replaced the notion of science as a homogeneous and universal method with that of it being a heterogeneous and local practice. In particular, Paul Feyerabend argued against there being any universal rules of science. Historian of science Daniel Thurs maintains that the scientific method is a myth or, at best, an idealization; the scientific method is the process. As in other areas of inquiry, science can build on previous knowledge and develop a more sophisticated understanding of its topics of study over time.
This model can be seen to underlie the scientific revolution. The ubiquitous element in the model of the scientific method is empiricism, or more epistemologic sensualism; this is in opposition to stringent forms of rationalism: the scientific method embodies that reason alone cannot solve a particular scientific problem. A strong formulation of the scientific method is not always aligned with a form of empiricism in which the empirical data is put forward in the form of experience or other abstracted forms of knowledge; the scientific method is of necessity als
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1