quinine quinine quinine is a medication used to treat malaria and babesiosis. this includes the treatment of malaria due to plasmodium falciparum that is resistant to chloroquine when artesunate is not available. while sometimes used for nocturnal leg cramps, quinine is not recommended for this purpose due to the risk of serious side effects. it can be taken by mouth or intravenously. malaria resistance to quinine occurs in certain areas of the world. quinine is also used as an ingredient in tonic water to impart a bitter taste. not to be confused with quinidine, quinone, quinoline, or chloroquine. quinineclinical datapronunciationus: /ˈkwaɪnaɪn/, /kwɪˈniːn/ or uk: /ˈkwɪniːn/ kwin-een trade namesqualaquin, quinbisul, othersahfs/drugs.commonographmedlineplusa682322license data us dailymed: quinine us fda: quinine pregnancycategory au: d routes ofadministrationby mouth, intramuscular, intravenous, rectalatc codem09aa01 (who) p01bc01 (who)legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic dataprotein binding70–95%metabolismliver (mostly cyp3a4 and cyp2c19-mediated)elimination half-life8–14 hours (adults), 6–12 hours (children)excretionkidney (20%)identifiers iupac name (r)-(6-methoxyquinolin-4-yl)methanol cas number130-95-0 ypubchem cid8549iuphar/bps2510drugbankdb00468 ychemspider84989 yuniia7v27phc7akeggd08460 ychebichebi:15854 nchemblchembl170 ycomptox dashboard (epa)dtxsid0044280 echa infocard100.004.550 chemical and physical dataformulac20h24n2o2molar mass324.424 g·mol−13d model (jsmol)interactive imagemelting point177 °c (351 °f) smiles 1((c2=cc=nc3=cc=c(c=c23)oc)o)c4cc1c4c=c inchi inchi=1s/c20h24n2o2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23h,1,7,9-10,12h2,2h3/t13-,14-,19-,20+/m0/s1 ykey:louprkontzgtke-wzblmqshsa-n y ny (what is this?) (verify) common side effects include headache, ringing in the ears, vision issues, and sweating. more severe side effects include deafness, low blood platelets, and an irregular heartbeat. use can make one more prone to sunburn. while it is unclear if use during pregnancy causes harm to the baby, treating malaria during pregnancy with quinine when appropriate is still recommended. quinine is an alkaloid, a naturally occurring chemical compound. how it works as a medicine is not entirely clear. quinine was first isolated in 1820 from the bark of a cinchona tree, which is native to peru, and its molecular formula was determined by strecker in 1854. the class of chemical compounds to which it belongs is thus called the cinchona alkaloids. bark extracts had been used to treat malaria since at least 1632 and it was introduced to spain as early as 1636 by jesuit missionaries returning from the new world. it is on the world health organization's list of essential medicines. treatment of malaria with quinine marks the first known use of a chemical compound to treat an infectious disease. uses medical as of 2006, quinine is no longer recommended by the world health organization (who) as a first-line treatment for malaria, because there are other substances that are equally effective with fewer side effects. they recommend that it be used only when artemisinins are not available. quinine is also used to treat lupus and arthritis. quinine was frequently prescribed as an off-label treatment for leg cramps at night, but this has become less common due to a warning from the us food and drug administration (fda) that such practice is associated with life-threatening side effects. quinine can also act as a competitive inhibitor of monoamine oxidase (mao), an enzyme that removes neurotransmitters from the brain. as an mao inhibitor, it has potential to serve as a treatment for individuals with psychological disorders similar to antidepressants that inhibit mao. available forms quinine is a basic amine and is usually provided as a salt. various existing preparations include the hydrochloride, dihydrochloride, sulfate, bisulfate and gluconate. in the united states, quinine sulfate is commercially available in 324-mg tablets under the brand name qualaquin. all quinine salts may be given orally or intravenously (iv); quinine gluconate may also be given intramuscularly (im) or rectally (pr). the main problem with the rectal route is that the dose can be expelled before it is completely absorbed; in practice, this is corrected by giving a further half dose. no injectable preparation of quinine is licensed in the us; quinidine is used instead. quinine base in various salts name quinine base equivalence quinine base 100 mg quinine bisulfate 169 mg quinine dihydrochloride 122 mg quinine gluconate 160 mg quinine hydrochloride 111 mg quinine sulfate dihydrate 121 mg beverages tonic water, in normal light and ultraviolet "black light". the quinine content of tonic water causes it to fluoresce under black light. quinine is a flavor component of tonic water and bitter lemon drink mixers. on the soda gun behind many bars, tonic water is designated by the letter "q" representing quinine. tonic water was initially marketed as a means of delivering quinine to consumers in order to offer anti-malarial protection. according to tradition, because of the bitter taste of anti-malarial quinine tonic, british colonials in india mixed it with gin to make it more palatable, thus creating the gin and tonic cocktail, which is still popular today. while it is possible to drink enough tonic water to temporarily achieve quinine levels that offer anti-malarial protection, it is not a sustainable long-term means of protection. in france, quinine is an ingredient of an apéritif known as quinquina, or "cap corse", and the wine-based apéritif dubonnet. in spain, quinine (also known as "peruvian bark" for its origin from the native cinchona tree) is sometimes blended into sweet malaga wine, which is then called "malaga quina". in italy, the traditional flavoured wine barolo chinato is infused with quinine and local herbs, and is served as a digestif. in scotland, the company a.g. barr uses quinine as an ingredient in the carbonated and caffeinated beverage irn-bru. in uruguay and argentina, quinine is an ingredient of a pepsico tonic water named paso de los toros. in denmark, it is used as an ingredient in the carbonated sports drink faxe kondi made by royal unibrew. as a flavouring agent in drinks, quinine is limited to less than 83 parts per million in the united states, and 100 mg⁄l in the european union. scientific quinine (and quinidine) are used as the chiral moiety for the ligands used in sharpless asymmetric dihydroxylation as well as for numerous other chiral catalyst backbones. because of its relatively constant and well-known fluorescence quantum yield, quinine is used in photochemistry as a common fluorescence standard. contraindications because of the narrow difference between its therapeutic and toxic effects, quinine is a common cause of drug-induced disorders, including thrombocytopenia and thrombotic microangiopathy. even from minor levels occurring in common beverages, quinine can have severe adverse effects involving multiple organ systems, among which are immune system effects and fever, hypotension, hemolytic anemia, acute kidney injury, liver toxicity, and blindness. in people with atrial fibrillation, conduction defects, or heart block, quinine can cause heart arrhythmias, and should be avoided. quinine can cause hemolysis in g6pd deficiency (an inherited deficiency), but this risk is small and the physician should not hesitate to use quinine in people with g6pd deficiency when there is no alternative. adverse effects quinine can cause unpredictable serious and life-threatening blood and cardiovascular reactions including low platelet count and hemolytic–uremic syndrome/thrombotic thrombocytopenic purpura (hus/ttp), long qt syndrome and other serious cardiac arrhythmias including torsades de pointes, blackwater fever, disseminated intravascular coagulation, leukopenia, and neutropenia. some people who have developed ttp due to quinine have gone on to develop kidney failure. it can also cause serious hypersensitivity reactions including anaphylactic shock, urticaria, serious skin rashes, including stevens–johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, granulomatous hepatitis, and itchiness. the most common adverse effects involve a group of symptoms called cinchonism, which can include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception. more severe cinchonism includes vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in heart rhythms. cinchonism is much less common when quinine is given by mouth, but oral quinine is not well tolerated (quinine is exceedingly bitter and many people will vomit after ingesting quinine tablets). other drugs, such as fansidar (sulfadoxine with pyrimethamine) or malarone (proguanil with atovaquone), are often used when oral therapy is required. quinine ethyl carbonate is tasteless and odourless, but is available commercially only in japan. blood glucose, electrolyte and cardiac monitoring are not necessary when quinine is given by mouth. quinine has diverse unwanted interactions with numerous prescription drugs, such as potentiating the anticoagulant effects of warfarin. mechanism of action quinine is used for its toxicity to the malarial pathogen, plasmodium falciparum, by interfering with its ability to dissolve and metabolize hemoglobin. as with other quinoline antimalarial drugs, the precise mechanism of action of quinine has not been fully resolved, although in vitro studies indicate it inhibits nucleic acid and protein synthesis, and inhibits glycolysis in p. falciparum. the most widely accepted hypothesis of its action is based on the well-studied and closely related quinoline drug, chloroquine. this model involves the inhibition of hemozoin biocrystallization in the heme detoxification pathway, which facilitates the aggregation of cytotoxic heme. free cytotoxic heme accumulates in the parasites, causing their deaths. quinine may target the malaria purine nucleoside phosphorylase enzyme. chemistry the uv absorption of quinine peaks around 350 nm (in uva). fluorescent emission peaks at around 460 nm (bright blue/cyan hue). quinine is highly fluorescent (quantum yield ~0.58) in 0.1 m sulfuric acid solution. synthesis cinchona trees remain the only economically practical source of quinine. however, under wartime pressure during world war ii, research towards its synthetic production was undertaken. a formal chemical synthesis was accomplished in 1944 by american chemists r.b. woodward and w.e. doering. since then, several more efficient quinine total syntheses have been achieved, but none of them can compete in economic terms with isolation of the alkaloid from natural sources. the first synthetic organic dye, mauveine, was discovered by william henry perkin in 1856 while he was attempting to synthesize quinine. biosynthesis quinine biosynthesis in the first step of quinine biosynthesis, the enzyme strictosidine synthase catalyzes a stereoselective pictet–spengler reaction between tryptamine and secologanin to yield strictosidine. suitable modification of strictosidine leads to an aldehyde. hydrolysis and decarboxylation would initially remove one carbon from the iridoid portion and produce corynantheal. then the tryptamine side-chain were cleaved adjacent to the nitrogen, and this nitrogen was then bonded to the acetaldehyde function to yield cinchonaminal. ring opening in the indole heterocyclic ring could generate new amine and keto functions. the new quinoline heterocycle would then be formed by combining this amine with the aldehyde produced in the tryptamine side-chain cleavage, giving cinchonidinone. for the last step, hydroxylation and methylation gives quinine. catalysis quinine and other cinchona alkaloids can be used as catalysts for stereoselective reactions in organic synthesis.: table 3b plate 560 for example, the quinine-catalyzed michael addition of a malononitrile to α,β-enones gives a high degree of sterechemical control. history