Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the 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 been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open 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 considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of 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; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is 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, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Phosphoryl chloride is a colourless liquid with the formula POCl3. It hydrolyses in moist air releasing phosphoric acid and fumes of hydrogen chloride, it is manufactured industrially on a large scale from phosphorus trichloride and oxygen or phosphorus pentoxide. It is used to make phosphate esters such as tricresyl phosphate. Like phosphate, phosphoryl chloride is tetrahedral in shape, it features three P−Cl bonds and one strong P=O double bond, with an estimated bond dissociation energy of 533.5 kJ/mol. On the basis of bond length and electronegativity, the Schomaker-Stevenson rule suggests that the double bond form is dominant, in contrast with the case of POF3; the P=O bond involves the donation of the lone pair electrons on oxygen p-orbitals to the antibonding combinations associated with phosphorus-chlorine bonds, thus constituting π bonding. With a freezing point of 1 °C and boiling point of 106 °C, the liquid range of POCl3 is rather similar to water. Like water, POCl3 autoionizes, owing to the reversible formation of POCl2+,Cl−.
POCl3 reacts with water to give hydrogen chloride and phosphoric acid: O=PCl3 + 3 H2O → O=P3 + 3 HClIntermediates in the conversion have been isolated, including pyrophosphoryl chloride, P2O3Cl4. Upon treatment with excess alcohols and phenols, POCl3 gives phosphate esters: O=PCl3 + 3 ROH → O=P3 + 3 HClSuch reactions are performed in the presence of an HCl acceptor such as pyridine or an amine. POCl3 can act as a Lewis base, forming adducts with a variety of Lewis acids such as titanium tetrachloride: Cl3PO + TiCl4 → Cl3POTiCl4The aluminium chloride adduct is quite stable, so POCl3 can be used to remove AlCl3 from reaction mixtures, for example at the end of a Friedel-Crafts reaction. POCl3 reacts with hydrogen bromide in the presence of Lewis-acidic catalysts to produce POBr3. Phosphoryl chloride can be prepared by many methods. Phosphoryl chloride was first reported in 1847 by the French chemist Adolphe Wurtz by reacting phosphorus pentachloride with water; the commercial method involves oxidation of phosphorus trichloride with oxygen: 2 PCl3 + O2 → 2 POCl3A related reaction include the oxidation of phosphorus trichloride with potassium chlorate: 3 PCl3 + KClO3 → 3 POCl3 + KCl The reaction of phosphorus pentachloride with phosphorus pentoxide.
6 PCl5 + P4O10 → 10 POCl3The reaction can be simplified by chlorinating a mixture of PCl3 and P4O10, generating the PCl5 in situ. The reaction of phosphorus pentachloride with boric acid or oxalic acid: 3 PCl5 + 2 B3 → 3 POCl3 + B2O3 + 6 HCl PCl5 + 2 → POCl3 + CO + CO2 + 2 HCl Reduction of tricalcium phosphate with carbon in the presence of chlorine gas: Ca32 + 6 C + 6 Cl2 → 3 CaCl2 + 6 CO + 2 POCl3The reaction of phosphorus pentoxide with sodium chloride is reported: 2 P2O5 + 3 NaCl → 3 NaPO3 + POCl3. In one commercial application, phosphoryl chloride is used in the manufacture of phosphate esters. Triarylphosphates such as triphenyl phosphate and tricresyl phosphate are used as flame retardants and plasticisers for PVC. Trialkylphosphates such as tributyl phosphate are used as liquid–liquid extraction solvents in nuclear reprocessing and elsewhere. In the semiconductor industry, POCl3 is used as a safe liquid phosphorus source in diffusion processes; the phosphorus acts. In the laboratory, POCl3 is a reagent in dehydrations.
One example involves conversion of primary amides to nitriles: RCNH2 + POCl3 → RCN + "PO2Cl" + 2 HClIn a related reaction, certain aryl-substituted amides can be cyclised using the Bischler-Napieralski reaction. Such reactions are believed to proceed via an imidoyl chloride. In certain cases, the imidoyl chloride is the final product. For example and pyrimidones can be converted to chloro- derivatives such as 2-chloropyridines and 2-chloropyrimidines, which are intermediates in the pharmaceutical industry. In the Vilsmeier-Haack reaction, POCl3 reacts with amides to produce a "Vilsmeier reagent", a chloro-iminium salt, which subsequently reacts with electron-rich aromatic compounds to produce aromatic aldehydes upon aqueous work-up
A nitrile is any organic compound that has a −C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate, used in super glue, nitrile rubber, a nitrile-containing polymer used in latex-free laboratory and medical gloves. Nitrile rubber is widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as cyanocarbons. Inorganic compounds containing the − C ≡ N group cyanides instead. Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic; the N−C−C geometry is linear in nitriles, reflecting the sp hybridization of the triply bonded carbon. The C−N distance is short at 1.16 Å, consistent with a triple bond. Nitriles are polar; as liquids, they have high relative permittivities in the 30s. The first compound of the homolog row of nitriles, the nitrile of formic acid, hydrogen cyanide was first synthesized by C. W. Scheele in 1782.
In 1811 J. L. Gay-Lussac was able to prepare the toxic and volatile pure acid. Around 1832 benzonitrile, the nitrile of benzoic acid, was prepared by Friedrich Wöhler and Justus von Liebig, but due to minimal yield of the synthesis neither physical nor chemical properties were determined nor a structure suggested. In 1834 Théophile-Jules Pelouze synthesized propionitrile, suggesting it to be an ether of propionic alcohol and hydrocyanic acid; the synthesis of benzonitrile by Hermann Fehling in 1844 by heating ammonium benzoate was the first method yielding enough of the substance for chemical research. Fehling determined the structure by comparing his results to the known synthesis of hydrogen cyanide by heating ammonium formate, he coined the name "nitrile" for the newfound substance, which became the name for this group of compounds. Industrially, the main methods for producing nitriles are hydrocyanation. Both routes are green in the sense. In ammoxidation, a hydrocarbon is oxidized in the presence of ammonia.
This conversion is practiced on a large scale for acrylonitrile: CH3CH=CH2 + 3⁄2 O2 + NH3 → NCCH=CH2 + 3 H2OIn the production of acrylonitrile, a side product is acetonitrile. On an industrial scale, several derivatives of benzonitrile, phthalonitrile, as well as Isobutyronitrile are prepared by ammoxidation; the process is assumed to proceed via the imine. Hydrocyanation is an industrial method for producing nitriles from hydrogen cyanide and alkenes; the process requires homogeneous catalysts. An example of hydrocyanation is the production of adiponitrile, a precursor to nylon-6,6 from 1,3-butadiene: CH2=CH−CH=CH2 + 2 HCN → NC4CN Two salt metathesis reactions are popular for laboratory scale reactions. In the Kolbe nitrile synthesis, alkyl halides undergo nucleophilic aliphatic substitution with alkali metal cyanides. Aryl nitriles are prepared in the Rosenmund-von Braun synthesis; the cyanohydrins are a special class of nitriles. Classically they result from the addition of alkali metal cyanides to aldehydes in the cyanohydrin reaction.
Because of the polarity of the organic carbonyl, this reaction requires no catalyst, unlike the hydrocyanation of alkenes. O-Silyl cyanohydrins are generated by the addition trimethylsilyl cyanide in the presence of a catalyst. Cyanohydrins are prepared by transcyanohydrin reactions starting, for example, with acetone cyanohydrin as a source of HCN. Nitriles can be prepared by the dehydration of primary amides. In the presence of ethyl dichlorophosphate and DBU benzamide converts to benzonitrile: Other reagents that are common used for this purpose include P4O10, SOCl2. Two intermediates in this reaction are amide tautomer A and its phosphate adduct B. In a related dehydration, secondary amides give nitriles by the von Braun amide degradation. In this case, one C-N bond is cleaved; the dehydration of aldoximes affords nitriles. Typical reagents for this transformation are triethylamine/sulfur dioxide, zeolites, or sulfuryl chloride. Exploiting this approach is the One-pot synthesis of nitriles from aldehyde with hydroxylamine in the presence of sodium sulfate.
From aryl carboxylic acids Aromatic nitriles are prepared in the laboratory from the aniline via diazonium compounds. This is the Sandmeyer reaction, it requires transition metal cyanides. ArN+2 + CuCN → ArCN + N2 + Cu+ A commercial source for the cyanide group is diethylaluminum cyanide Et2AlCN which can be prepared from triethylaluminium and HCN, it has been used in nucleophilic addition to ketones. For an example of its use see: Kuwajima Taxol total synthesis cyanide ions facilitate the coupling of dibromides. Reaction of α,α′-dibromoadipic acid with sodium cyanide in ethanol yields the cyano cyclobutane: In the so-called Franchimont Reaction an α-bromocarboxylic acid is dimerized after hydrolysis of the cyanogroup and decarboxylationAromatic nitriles can be prepared from base hydrolysis of trichloromethyl aryl ketimines in the Houben-Fischer synthesis Nitriles can be obtained from primary amines via oxidation. Common methods include the use of potassium persulfate, Trichloroisocyanuric acid, or anodic electrosynthesis.
Α-Amino acids form nitriles and carbon dioxide via various means of oxidative decarboxylation. Henry Drysdale Dakin discovered this oxidation in 1916. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditio
Phenol is an aromatic organic compound with the molecular formula C6H5OH. It is a white crystalline solid, volatile; the molecule consists of a phenyl group bonded to a hydroxy group. It requires careful handling due to its propensity for causing chemical burns. Phenol was first extracted from coal tar, it is an important industrial commodity as a precursor to useful compounds. It is used to synthesize plastics and related materials. Phenol and its chemical derivatives are essential for production of polycarbonates, Bakelite, detergents, herbicides such as phenoxy herbicides, numerous pharmaceutical drugs. Phenol is an organic compound appreciably soluble in water, with about 84.2 g dissolving in 1000 mL. Homogeneous mixtures of phenol and water at phenol to water mass ratios of ~2.6 and higher are possible. The sodium salt of phenol, sodium phenoxide, is far more water-soluble. Phenol is weakly acidic and at high pHs gives the phenolate anion C6H5O−: PhOH ⇌ PhO− + H+ Compared to aliphatic alcohols, phenol is about 1 million times more acidic, although it is still considered a weak acid.
It reacts with aqueous NaOH to lose H+, giving the salt sodium phenoxide, whereas most alcohols react only partially. One explanation for the increased acidity over alcohols is resonance stabilization of the phenoxide anion by the aromatic ring. In this way, the negative charge on oxygen is delocalized on to the ortho and para carbon atoms through the pi system. An alternative explanation involves the sigma framework, postulating that the dominant effect is the induction from the more electronegative sp2 hybridised carbons. In support of the second explanation, the pKa of the enol of acetone in water is 10.9, making it only less acidic than phenol. Thus, the greater number of resonance structures available to phenoxide compared to acetone enolate seems to contribute little to its stabilization. However, the situation changes. A recent in silico comparison of the gas phase acidities of the vinylogues of phenol and cyclohexanol in conformations that allow for or exclude resonance stabilization leads to the inference that about 1⁄3 of the increased acidity of phenol is attributable to inductive effects, with resonance accounting for the remaining difference.
The phenoxide anion has a similar nucleophilicity to free amines, with the further advantage that its conjugate acid does not become deactivated as a nucleophile in moderately acidic conditions. Phenolate esters are more stable toward hydrolysis than acid anhydrides and acyl halides but are sufficiently reactive under mild conditions to facilitate the formation of amide bonds. Phenol exhibits keto-enol tautomerism with its unstable keto tautomer cyclohexadienone, but only a tiny fraction of phenol exists as the keto form; the equilibrium constant for enolisation is 10−13, which means only one in every ten trillion molecules is in the keto form at any moment. The small amount of stabilisation gained by exchanging a C=C bond for a C=O bond is more than offset by the large destabilisation resulting from the loss of aromaticity. Phenol therefore exists entirely in the enol form. Phenoxides are enolates stabilised by aromaticity. Under normal circumstances, phenoxide is more reactive at the oxygen position, but the oxygen position is a "hard" nucleophile whereas the alpha-carbon positions tend to be "soft".
Phenol is reactive toward electrophilic aromatic substitution as the oxygen atom's pi electrons donate electron density into the ring. By this general approach, many groups can be appended to the ring, via halogenation, acylation and other processes. However, phenol's ring is so activated—second only to aniline—that bromination or chlorination of phenol leads to substitution on all carbon atoms ortho and para to the hydroxy group, not only on one carbon. Phenol reacts with dilute nitric acid at room temperature to give a mixture of 2-nitrophenol and 4-nitrophenol while with concentrated nitric acid, more nitro groups get substituted on the ring to give 2,4,6-trinitrophenol, known as picric acid. Aqueous solutions of phenol are weakly acidic and turn blue litmus to red. Phenol is neutralized by sodium hydroxide forming sodium phenate or phenolate, but being weaker than carbonic acid, it cannot be neutralized by sodium bicarbonate or sodium carbonate to liberate carbon dioxide. C6H5OH + NaOH → C6H5ONa + H2OWhen a mixture of phenol and benzoyl chloride are shaken in presence of dilute sodium hydroxide solution, phenyl benzoate is formed.
This is an example of the Schotten-Baumann reaction: C6H5OH + C6H5COCl → C6H5OCOC6H5 + HClPhenol is reduced to benzene when it is distilled with zinc dust, or when phenol vapour is passed over granules of zinc at 400 °C: C6H5OH + Zn → C6H6 + ZnOWhen phenol is reacted with diazomethane in the presence of boron trifluoride, anisole is obtained as the main product and nitrogen gas as a byproduct. C6H5OH + CH2N2 → C6H5OCH3 + N2When phenol reacts with iron chloride solution, an intense violet-purple solution is formed; because of phenol's commercial importance, many methods have been developed for its production. The dominant current route, accounting for 95% of production, is the cumene process, which uses benzene and propene as feedstock and involves the partial oxidation of cumene vi
Chromium trioxide is an inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, is sometimes marketed under the same name; this compound is a dark-purple solid under anhydrous conditions, bright orange when wet and which dissolves in water concomitant with hydrolysis. Millions of kilograms are produced annually for electroplating. Chromium trioxide is a suspected carcinogen. Chromium trioxide is generated by treating sodium chromate or the corresponding sodium dichromate with sulfuric acid: H2SO4 + Na2Cr2O7 → 2 CrO3 + Na2SO4 + H2OApproximately 100M kg are produced annually by this or similar routes; the solid consists of chains of tetrahedrally coordinated chromium atoms that share vertices. Each chromium center, shares two oxygen centers with neighbors. Two oxygen atoms are not shared, giving an overall stoichiometry of 1:3; the structure of monomeric CrO3 has been calculated using density functional theory, is predicted to be pyramidal rather than planar. Chromium trioxide decomposes above 197 °C liberating oxygen giving Cr2O3: 4 CrO3 → 2 Cr2O3 + 3 O2It is used in organic synthesis as an oxidant as a solution in acetic acid, or acetone in the case of the Jones oxidation.
In these oxidations, the Cr converts primary alcohols to the corresponding carboxylic acids and secondary alcohols to ketones. The reactions are given below: Primary alcohols4 CrO3 + 3 RCH2OH + 12 H+ → 3 RCOOH + 4 Cr3+ + 9 H2OSecondary alcohols2 CrO3 + 3 R2CHOH + 6 H+ → 3 R2C=O + 2 Cr3+ + 6 H2O Chromium trioxide is used in chrome plating, it is employed with additives that affect the plating process but do not react with the trioxide. The trioxide reacts with cadmium and other metals to generate passivating chromate films that resist corrosion, it is used in the production of synthetic rubies. Chromic acid solution is used in applying types of anodic coating to aluminium, which are used in aerospace applications. A Chromic Acid/ Phosphoric Acid solution is the preferred stripping agent of anodic coatings of all types. Chromium trioxide is toxic and carcinogenic, it is the main example of an environmental hazard. The related chromium derivatives are not dangerous. Chromium trioxide, being a powerful oxidizer, will ignite organic materials such as alcohols on contact.
ATSDR Case Studies in Environmental Medicine: Chromium Toxicity U. S. Department of Health and Human Services Chromium Trioxide at The Periodic Table of Videos
A carboxylic acid is an organic compound that contains a carboxyl group. The general formula of a carboxylic acid is R–COOH, with R referring to the rest of the molecule. Carboxylic acids occur widely. Important examples include acetic acid. Deprotonation of a carboxyl group gives a carboxylate anion. Important carboxylate salts are soaps. Carboxylic acids are identified by their trivial names, they have the suffix -ic acid. IUPAC-recommended names exist. For example, butyric acid is butanoic acid by IUPAC guidelines. For nomenclature of complex molecules containing a carboxylic acid, the carboxyl can be considered position one of the parent chain if there are other substituents, for example, 3-chloropropanoic acid. Alternately, it can be named as a "carboxy" or "carboxylic acid" substituent on another parent structure, for example, 2-carboxyfuran; the carboxylate anion of a carboxylic acid is named with the suffix -ate, in keeping with the general pattern of -ic acid and -ate for a conjugate acid and its conjugate base, respectively.
For example, the conjugate base of acetic acid is acetate. Carboxylic acids are polar; because they are both hydrogen-bond acceptors and hydrogen-bond donors, they participate in hydrogen bonding. Together the hydroxyl and carbonyl group forms the functional group carboxyl. Carboxylic acids exist as dimers in nonpolar media due to their tendency to "self-associate". Smaller carboxylic acids are soluble in water, whereas higher carboxylic acids have limited solubility due to the increasing hydrophobic nature of the alkyl chain; these longer chain acids tend to be rather soluble in less-polar solvents such as ethers and alcohols. Hydrophobic carboxylic acids react aqueous sodium hydroxide to give water soluble sodium salts. For example, enathic acid has a small solubility in water, but its sodium salt is soluble in water: Carboxylic acids tend to have higher boiling points than water, not only because of their increased surface area, but because of their tendency to form stabilised dimers through hydrogen bonds.
For boiling to occur, either the dimer bonds must be broken or the entire dimer arrangement must be vaporised, both of which increase the enthalpy of vaporization requirements significantly. Carboxylic acids are Brønsted -- Lowry acids, they are the most common type of organic acid. Carboxylic acids are weak acids, meaning that they only dissociate into H3O+ cations and RCOO− anions in neutral aqueous solution. For example, at room temperature, in a 1-molar solution of acetic acid, only 0.4% of the acid are dissociated. Electron-withdrawing substituents, such as -CF3 group, give stronger acids. Electron-donating substituents give weaker acids Deprotonation of carboxylic acids gives carboxylate anions; each of the carbon–oxygen bonds in the carboxylate anion has a partial double-bond character. The carbonyl carbon's partial positive charge is weakened by the -1/2 negative charges on the 2 oxygen atoms. Carboxylic acids have strong sour odors. Esters of carboxylic acids tend to have pleasant odors, many are used in perfume.
Carboxylic acids are identified as such by infrared spectroscopy. They exhibit a sharp band associated with vibration of the C–O vibration bond between 1680 and 1725 cm−1. A characteristic νO–H band appears as a broad peak in the 2500 to 3000 cm−1 region. By 1H NMR spectrometry, the hydroxyl hydrogen appears in the 10–13 ppm region, although it is either broadened or not observed owing to exchange with traces of water. Many carboxylic acids are produced industrially on a large scale, they are pervasive in nature. Esters of fatty acids are the main components of lipids and polyamides of aminocarboxylic acids are the main components of proteins. Carboxylic acids are used in the production of polymers, pharmaceuticals and food additives. Industrially important carboxylic acids include acetic acid and methacrylic acids, adipic acid, citric acid, ethylenediaminetetraacetic acid, fatty acids, maleic acid, propionic acid, terephthalic acid. In general, industrial routes to carboxylic acids differ from those used on smaller scale because they require specialized equipment.
Carbonylation of alcohols as illustrated by the Cativa process for production of acetic acid. Formic acid is prepared by a different carbonylation pathway starting from methanol. Oxidation of aldehydes with air using cobalt and manganese catalysts; the required aldehydes are obtained from alkenes by hydroformylation. Oxidation of hydrocarbons using air. For simple alkanes, this method is inexpensive but not selective enough to be useful. Allylic and benzylic compounds undergo more selective oxidations. Alkyl groups on a benzene ring are oxidized to the carboxylic acid, regardless of its chain length. Benzoic acid from toluene, terephthalic acid from para-xylene, phthalic acid from ortho-xylene are illustrative large-scale conversions. Acrylic acid is generated from propene. Base-cata
Sumatriptan, sold under the brand name Imitrex among others, is a medication used to treat migraine headaches and cluster headaches. It is taken in the nose, or by injection under the skin. Effects occur within three hours. Common side effects include chest pressure, feeling tired, feeling of the world spinning, tingling. Serious side effects may include serotonin syndrome, heart attacks and seizures. With excessive use medication overuse headaches may occur, it is unclear if use in breastfeeding is safe. How it works is not clear, it is in the triptan class of medications. Sumatriptan was patented in 1982 and approved for medical use in 1991, it is avaliable as a generic medication. In the United Kingdom it costs the NHS about £1 per dose as of 2019. In the United States the wholesale cost of this amount is about $0.60 USD. In 2016 it was the 115th most prescribed medication in the United States with more than 6 million prescriptions, it is avaliable as the combination product sumatriptan/naproxen at a cost of 50 USD per dose.
Sumatriptan is effective for relieving the intensity of migraine and cluster headaches. It is most effective. Injected sumatriptan is more effective than other formulations. Overdose of sumatriptan can cause sulfhemoglobinemia, a rare condition in which the blood changes from red to green, due to the integration of sulfur into the hemoglobin molecule. If sumatriptan is discontinued, the condition reverses within a few weeks. Serious cardiac events, including some that have been fatal, have occurred following the use of sumatriptan injection or tablets. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, ventricular fibrillation; the most common side effects reported by at least 2% of patients in controlled trials of sumatriptan for migraine are atypical sensations reported by 4% in the placebo group and 5–6% in the sumatriptan groups and other pressure sensations reported by 4% in the placebo group and 6–8% in the sumatriptan groups, neurological events reported by less than 1% in the placebo group and less than 1% to 2% in the sumatriptan groups.
Malaise/fatigue occurred in 2 -- 3 % of the sumatriptan groups. Sleep disturbance occurred in less than 1% in the placebo group to 2% in the sumatriptan group. Sumatriptan is structurally similar to serotonin, is a 5-HT receptor agonist. Sumatriptan's primary therapeutic effect, however, is in its inhibition of the release of Calcitonin gene-related peptide through its 5-HT1D/1B receptor-agonist action; this is substantiated by the efficacy of newly developed CGRP antagonists and antibodies in the preventative treatment of migraine. However, how agonism of the 5-HT1D/1B receptors inhibits CGRP release is not understood. CGRP is believed to cause sensitization of trigeminal nociceptive neurons, contributing to the pain experienced in migraine. Sumatriptan is shown to decrease the activity of the trigeminal nerve, which accounts for sumatriptan's efficacy in treating cluster headaches; the injectable form of the drug has been shown to abort a cluster headache within 30 minutes in 77% of cases. Sumatriptan is administered in several forms: tablets, subcutaneous injection, nasal spray.
Oral administration suffers from poor bioavailability due to presystemic metabolism—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. A new rapid-release tablet formulation has the same bioavailability, but the maximum concentration is achieved on average 10–15 minutes earlier; when injected, sumatriptan is faster-acting. Sumatriptan is metabolised by monoamine oxidase A into 2‐acetic acid, conjugated to glucuronic acid; these metabolites are excreted in the bile. Only about 3% of the active drug may be recovered unchanged. There is no simple, direct relationship between sumatriptan concentration per se in the blood and its anti-migraine effect; this paradox has, to some extent, been resolved by comparing the rates of absorption of the various sumatriptan formulations, rather than the absolute amounts of drug that they deliver. In 1991, Glaxo received approval for sumatriptan, the first available triptan. In the United States, it is available only by medical prescription.
This requirement for a medical prescription exists in Australia. However, it can be bought over the counter in the Sweden. Several dosage forms for sumatriptan have been approved, including tablets, solution for injection, nasal inhalers. In July 2009, the US FDA approved a single-use jet injector formulation of sumatriptan; the device delivers a subcutaneous injection of 6 mg sumatriptan, without the use of a needle. Autoinjectors with needles have been available in Europe and North America for several years. Phase III studies with a iontophoretic transdermal patch started in July 2008; this patch uses low voltage controlled by a pre-programmed microchip to deliver a single dose of sumatriptan through the skin within 30 minutes. Zecuity was approved by the US FDA in January 2013. Sales of Zecuity have been stopped following reports of irritation. Glaxo patents for sumatriptan expired in February 2009. At that time, Imitrex