Cytisine
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| Other names | Cytisine; Baptitoxine; Sophorine |
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| ECHA InfoCard | 100.006.924 |
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| Formula | C11H14N2O |
| Molar mass | 190.246g·mol−1 |
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| Melting point | 152 °C (306 °F) |
| Boiling point | 218 °C (424 °F) |
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Cytisine,also known asbaptitoxine,cytisinicline,orsophorine,is analkaloidthat occurs naturally in several plant genera, such asLaburnumandCytisusof the familyFabaceae.It has been used medically to help withsmoking cessation.[1]Although widely used for smoking cessation in Eastern Europe, cytisine remains relatively unknown beyond it.[citation needed]However, it has been found effective in several randomizedclinical trials,including some in the United States and a large one in New Zealand,[1]and is being investigated in additional trials in the United States (being conducted by Achieve Life Sciences) and anon-inferiority trialin Australia in which it is being compared head-to-head with the smoking cessation aidvarenicline(sold in the United States as Chantix).[2]It has also been usedentheogenicallyviamescalbeansby some Native American groups, historically in theRio Grande Valleypredating evenpeyote.[3]
Sources
[edit]Cytisine is extracted from the seeds ofCytisus laborinumL. (Golden Rain acacia), and is found in several genera of the subfamilyFaboideaeof the familyFabaceae,includingLaburnum,Anagyris,Thermopsis,Cytisus,Genista,RetamaandSophora.Cytisine is also present inGymnocladusof the subfamilyCaesalpinioideae.[citation needed]
Uses
[edit]Smoking cessation
[edit]Cytisine has been available inpost-Soviet statesfor more than 40 years as an aid to smoking cessation under the brand nameTabexfrom the Bulgarian pharmaceutical company Sopharma AD.[4]It was first marketed in Bulgaria in 1964 and then became widely available in the then-Soviet Union.[5]In Poland, it is sold under the brand nameDesmoxan,and it is also available in Canada under the brand nameCravv.[6][7]
Its molecular structure has some similarity to that ofnicotine,and it has similar pharmacological effects. Like the smoking cessation aidvarenicline,cytisine is a partialagonistofnicotinic acetylcholine receptors(nAChRs).[8]Cytisine has a shorthalf-lifeof 4.8 hours.[9]As a result, the extract provides smokers with satisfaction similar to smoking a cigarette, alleviating the urge to smoke and reducing the severity of nicotinewithdrawalsymptoms, while also reducing the reward experience of any cigarettes smoked.[10]
Cytisine is rapidly eliminated from the body.[medical citation needed]
In 2011, a randomized controlled trial with 740 patients found cytisine improved 12-month abstinence from nicotine from 2.4% with placebo to 8.4% with cytisine.[11]A 2013meta-analysisof eight studies demonstrated that cytisine has similar effectiveness tovareniclinebut with substantially lower side effects.[12]A 2014systematic reviewandeconomic evaluationconcluded that cytisine was more likely to be cost-effective for smoking cessation thanvarenicline.[13]
Recreational
[edit]Plants containing cytisine, including thescotch broomandmescalbean,have also been usedrecreationally.Positive effects are reported to include a nicotine-like intoxication.[11]
Reagent for organic chemistry
[edit](−)-Cytisine extracted fromLaburnum anagyroidesseeds was used as a starting material for the preparation of "(+)-sparteinesurrogate, "for the preparation of enantiomerically enriched lithium anions of opposite stereochemistry to those anions obtained from sparteine.[14]
Toxicity
[edit]Cytisine has been found to interfere with breathing and cause death in test mice;LD50i.v. in mice is about 2 mg/kg.[15]Cytisine is alsoteratogenic.[16]
Māmane (Sophora chrysophylla) can contain amounts of cytisine that are lethal to most animals. Thepalila(Loxioides bailleui,abird),Uresiphita polygonalis virescensandCydiaspecies (moths), and possiblysheepandgoatsare not affected by the toxin for various reasons, and use māmane, or parts thereof, as food.U. p. virescenscaterpillars are possibly able to sequester the cytisine to give themselves protection from getting eaten; they haveaposematiccoloration which would warn off potentialpredators.[17]
References
[edit]- ^abWalker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, et al. (December 2014)."Cytisine versus nicotine for smoking cessation".The New England Journal of Medicine.371(25): 2353–2362.doi:10.1056/nejmoa1407764.PMID25517706.S2CID13759117.
- ^Thomas D, Farrell M, McRobbie H, Tutka P, Petrie D, West R, et al. (May 2019)."The effectiveness, safety and cost-effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: a study protocol for a randomized controlled non-inferiority trial"(PDF).Addiction.114(5): 923–933.doi:10.1111/add.14541.PMID30589984.S2CID58621453.
- ^Howard JH (1957)."The Mescal Bean Cult of the Central and Southern Plains: An Ancestor of the Peyote Cult".American Anthropologist.59(1): 75–87.doi:10.1525/aa.1957.59.1.02a00070.JSTOR666531.
- ^Zatonski W, Cedzynska M, Tutka P, West R (December 2006)."An uncontrolled trial of cytisine (Tabex) for smoking cessation".Tobacco Control.15(6): 481–484.doi:10.1136/tc.2006.016097.PMC2563682.PMID17130378.
- ^"Old anti-smoking drug passes new test".Reuters.28 September 2011.Retrieved11 March2022.
- ^Prochaska JJ, Das S, Benowitz NL (August 2013)."Cytisine, the world's oldest smoking cessation aid".BMJ.347(aug23 1): f5198.doi:10.1136/bmj.f5198.PMID23974638.S2CID31845933.
- ^Zatoński W, Janik-Koncewicz K, Stępnicka Z, Zatońska K, Połtyn-Zaradna K, Herbeć A (2020)."History of smoking cessation treatment in Poland – the strengthening role of cytisine as the most effective and safe pharmacotherapy".Journal of Health Inequalities.6(2): 116–123.doi:10.5114/jhi.2020.102969.ISSN2450-5927.S2CID234956118.
- ^Dallanoce C, Frigerio F, Martelli G, Grazioso G, Matera C, Pomè DY, et al. (June 2010). "Novel tricyclic Delta(2)-isoxazoline and 3-oxo-2-methyl-isoxazolidine derivatives: synthesis and binding affinity at neuronal nicotinic acetylcholine receptor subtypes".Bioorganic & Medicinal Chemistry.18(12): 4498–4508.doi:10.1016/j.bmc.2010.04.065.PMID20478710.
- ^Jeong SH, Newcombe D, Sheridan J, Tingle M (June 2015). "Pharmacokinetics of cytisine, an α4 β2 nicotinic receptor partial agonist, in healthy smokers following a single dose".Drug Testing and Analysis.7(6): 475–482.doi:10.1002/dta.1707.PMID25231024.S2CID45441989.
- ^Reinberg S (17 December 2014)."Cheap Natural Compound May Help Smokers Quit. But cytisinicline isn't widely available, study authors note".WebMD.Retrieved4 June2021.
- ^abWest R, Zatonski W, Cedzynska M, Lewandowska D, Pazik J, Aveyard P, Stapleton J (September 2011)."Placebo-controlled trial of cytisine for smoking cessation".The New England Journal of Medicine.365(13): 1193–1200.doi:10.1056/NEJMoa1102035.PMID21991893.
- ^Hajek P, McRobbie H, Myers K (November 2013)."Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis".Thorax.68(11): 1037–1042.doi:10.1136/thoraxjnl-2012-203035.PMID23404838.
- ^Leaviss J, Sullivan W, Ren S, Everson-Hock E, Stevenson M, Stevens JW, et al. (May 2014)."What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation".Health Technology Assessment.18(33): 1–120.doi:10.3310/hta18330.PMC4780997.PMID24831822.
- ^"Synthesis of (+)-(1R,@S,9S)-11-Methyl-7,11-Diazatricyclo[7.3.1.02.7]tridecane, a (+)sparteine surrogate".Organic Syntheses.83:141. 2006.doi:10.15227/orgsyn.083.0141.
- ^The Merck Index, 10th Ed.(1983) p.402, Rahway: Merck & Co.
- ^Keeler RF.Handbook of Natural Toxins: Toxicology of Plant and Fungal Compounds.CRC Press. p. 43.
- ^Banko PC, Cipollini ML, Breton GW, Paulk E, Wink M, Izhaki I (July 2002)."Seed chemistry of Sophora chrysophylla (mamane) in relation to diet of specialist avian seed predator Loxioides bailleui (palila) in Hawaii"(PDF).Journal of Chemical Ecology.28(7): 1393–1410.doi:10.1023/A:1016248502927.PMID12199503.S2CID7064787.Archived fromthe original(PDF)on 21 December 2012.Retrieved4 May2007.
External links
[edit]
- "Cytisinicline".Drug Information Portal.U.S. National Library of Medicine.
