cytisine
{{Short description|Chemical compound}}
{{Distinguish|cytosine|cysteine|cystine|cytidine|cotinine}}
{{Use dmy dates|date=May 2022}}
{{Infobox drug
| image = (-)-Cytisine.svg
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| image2 = Cytisine 3D ball.png
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| DailyMedID = Cytisine
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| ATC_prefix = N07
| ATC_suffix = BA04
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| CAS_number = 485-35-8
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| PubChem = 10235
| IUPHAR_ligand = 5347
| DrugBank = DB09028
| ChemSpiderID = 9818
| UNII = 53S5U404NU
| KEGG =
| ChEBI = 4055
| ChEMBL = 497939
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| synonyms = Cytisine; Baptitoxine; Sophorine
| IUPAC_name = (1R,5S)-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a] [1,3]diazocin-8-one
| C=11 | H=14 | N=2 | O=1
| SMILES = O=C1/C=C\C=C2/N1C[C@@H]3CNC[C@H]2C3
| StdInChI = 1S/C11H14N2O/c14-11-3-1-2-10-9-4-8(5-12-6-9)7-13(10)11/h1-3,8-9,12H,4-7H2/t8-,9+/m0/s1
| StdInChIKey = ANJTVLIZGCUXLD-DTWKUNHWSA-N
| melting_point = 152
| boiling_point = 218
}}
Cytisine, also known as baptitoxine, cytisinicline, or sophorine, is an alkaloid that occurs naturally in several plant genera, such as Laburnum and Cytisus of the family Fabaceae. It has been used medically to help with smoking cessation.{{Cite journal |display-authors=6 |vauthors=Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C |date=December 2014 |title=Cytisine versus nicotine for smoking cessation |journal=The New England Journal of Medicine |volume=371 |issue=25 |pages=2353–2362 |doi=10.1056/nejmoa1407764 |pmid=25517706 |s2cid=13759117 |doi-access=free}} It has been found effective in several randomized clinical trials, including in the United States and New Zealand, and is being investigated in additional trials in the United States and a non-inferiority trial in Australia in which it is being compared head-to-head with the smoking cessation aid varenicline (sold in the United States as Chantix).{{Cite journal |display-authors=6 |vauthors=Thomas D, Farrell M, McRobbie H, Tutka P, Petrie D, West R, Siahpush M, Gartner C, Walker N, Mendelsohn CP, Hall W, Paul C, Zwar N, Ferguson SG, Boland VC, Richmond R, Doran CM, Shakeshaft A, Mattick RP, Courtney RJ |date=May 2019 |title=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 |url=https://pure.bond.edu.au/ws/files/32288121/AM_The_effectiveness_safety_and_cost_effectiveness_of_cytisine_versus_varenicline_for_smoking.pdf |journal=Addiction |volume=114 |issue=5 |pages=923–933 |doi=10.1111/add.14541 |pmid=30589984 |s2cid=58621453}} It has also been used entheogenically via mescalbeans by some Native American groups, historically in the Rio Grande Valley predating even peyote.{{Cite journal |vauthors=Howard JH |year=1957 |title=The Mescal Bean Cult of the Central and Southern Plains: An Ancestor of the Peyote Cult |journal=American Anthropologist |volume=59 |issue=1 |pages=75–87 |doi=10.1525/aa.1957.59.1.02a00070 |jstor=666531 |doi-access=free}}
Sources
Cytisine is extracted from the seeds of Cytisus laburnum L. (Golden Rain acacia), and is found in several genera of the subfamily Faboideae of the family Fabaceae, including Laburnum, Anagyris, Thermopsis, Cytisus, Genista, Retama and Sophora. Cytisine is also present in Gymnocladus of the subfamily Caesalpinioideae.{{fact|date=April 2022}}
Uses
=Smoking cessation=
Cytisine has been available in post-Soviet states for more than 40 years as an aid to smoking cessation under the brand name Tabex from the Bulgarian pharmaceutical company Sopharma AD.{{Cite journal |vauthors=Zatonski W, Cedzynska M, Tutka P, West R |date=December 2006 |title=An uncontrolled trial of cytisine (Tabex) for smoking cessation |journal=Tobacco Control |volume=15 |issue=6 |pages=481–484 |doi=10.1136/tc.2006.016097 |pmc=2563682 |pmid=17130378}} In 1961, Bulgarian pharmacist Strashimir Ingilizov synthesized Tabex using the alkaloid Cytisine which was derived from the seeds of the yellow acacia (Cytisus laburnum), a European decorative shrub prevalent in Bulgaria and commonly referred to as "golden rain".{{Cite journal |last=Gatsov |first=Nikolai |date=October 1964 |title=Ein Mittel Gegen Rauchen |journal=Bulgarien |volume=1 |pages=39}} It was first marketed in Bulgaria in 1964 and then became widely available in the Soviet Union.{{Cite news |date=28 September 2011 |title=Old anti-smoking drug passes new test |url=https://www.reuters.com/article/us-smoking-idINTRE78R66520110928 |access-date=11 March 2022 |work=Reuters |language=en}} In Poland, it is sold under the brand name Desmoxan, and it is also available in Canada under the brand name Cravv.{{Cite journal |vauthors=Prochaska JJ, Das S, Benowitz NL |date=August 2013 |title=Cytisine, the world's oldest smoking cessation aid |url=https://escholarship.org/uc/item/8qq3r737 |journal=BMJ |volume=347 |issue=aug23 1 |pages=f5198 |doi=10.1136/bmj.f5198 |pmid=23974638 |s2cid=31845933|url-access=subscription }}{{Cite journal |vauthors=Zatoński W, Janik-Koncewicz K, Stępnicka Z, Zatońska K, Połtyn-Zaradna K, Herbeć A |date=2020 |title=History of smoking cessation treatment in Poland – the strengthening role of cytisine as the most effective and safe pharmacotherapy |journal=Journal of Health Inequalities |volume=6 |issue=2 |pages=116–123 |doi=10.5114/jhi.2020.102969 |issn=2450-5927 |s2cid=234956118 |doi-access=free}}
Its molecular structure has some similarity to that of nicotine, and it has similar pharmacological effects. Like the smoking cessation aid varenicline, cytisine is a partial agonist of nicotinic acetylcholine receptors (nAChRs).{{Cite journal |display-authors=6 |vauthors=Dallanoce C, Frigerio F, Martelli G, Grazioso G, Matera C, Pomè DY, Pucci L, Clementi F, Gotti C, De Amici M |date=June 2010 |title=Novel tricyclic Delta(2)-isoxazoline and 3-oxo-2-methyl-isoxazolidine derivatives: synthesis and binding affinity at neuronal nicotinic acetylcholine receptor subtypes |journal=Bioorganic & Medicinal Chemistry |volume=18 |issue=12 |pages=4498–4508 |doi=10.1016/j.bmc.2010.04.065 |pmid=20478710}} Cytisine has a short half-life of 4.8 hours.{{Cite journal |vauthors=Jeong SH, Newcombe D, Sheridan J, Tingle M |date=June 2015 |title=Pharmacokinetics of cytisine, an α4 β2 nicotinic receptor partial agonist, in healthy smokers following a single dose |journal=Drug Testing and Analysis |volume=7 |issue=6 |pages=475–482 |doi=10.1002/dta.1707 |pmid=25231024 |s2cid=45441989}} As a result, the extract provides smokers with satisfaction similar to smoking a cigarette, alleviating the urge to smoke and reducing the severity of nicotine withdrawal symptoms, while also reducing the reward experience of any cigarettes smoked.{{Cite news |date=17 December 2014 |title=Cheap Natural Compound May Help Smokers Quit. But cytisinicline isn't widely available, study authors note |url=https://www.webmd.com/smoking-cessation/news/20141217/cheap-natural-compound-may-help-smokers-quit |access-date=4 June 2021 |work=WebMD |vauthors=Reinberg S}}
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.{{Cite journal |vauthors=West R, Zatonski W, Cedzynska M, Lewandowska D, Pazik J, Aveyard P, Stapleton J |date=September 2011 |title=Placebo-controlled trial of cytisine for smoking cessation |journal=The New England Journal of Medicine |volume=365 |issue=13 |pages=1193–1200 |doi=10.1056/NEJMoa1102035 |pmid=21991893 |doi-access=free}} A 2013 meta-analysis of eight studies demonstrated that cytisine has similar effectiveness to varenicline but with substantially lower side effects.{{Cite journal |vauthors=Hajek P, McRobbie H, Myers K |date=November 2013 |title=Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis |journal=Thorax |volume=68 |issue=11 |pages=1037–1042 |doi=10.1136/thoraxjnl-2012-203035 |pmid=23404838 |doi-access=free}} A 2014 systematic review and economic evaluation concluded that cytisine was more likely to be cost-effective for smoking cessation than varenicline.{{Cite journal |display-authors=6 |vauthors=Leaviss J, Sullivan W, Ren S, Everson-Hock E, Stevenson M, Stevens JW, Strong M, Cantrell A |date=May 2014 |title=What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation |journal=Health Technology Assessment |volume=18 |issue=33 |pages=1–120 |doi=10.3310/hta18330 |pmc=4780997 |pmid=24831822}}
=Recreational=
Plants containing cytisine, including the scotch broom and mescalbean, have also been used recreationally. Positive effects are reported to include a nicotine-like intoxication.
=Reagent for organic chemistry=
(−)-Cytisine extracted from Laburnum anagyroides seeds was used as a starting material for the preparation of "(+)- sparteine surrogate", for the preparation of enantiomerically enriched lithium anions of opposite stereochemistry to those anions obtained from sparteine.{{Cite journal |date=2006 |title=Synthesis of (+)-(1R,@S,9S)-11-Methyl-7,11-Diazatricyclo[7.3.1.02.7]tridecane, a (+)sparteine surrogate |journal=Organic Syntheses |volume=83 |page=141 |doi=10.15227/orgsyn.083.0141 |doi-access=free}}
Toxicity
Cytisine has been found to interfere with breathing and cause death in test mice; {{LD50}} i.v. in mice is about 2 mg/kg.The Merck Index, 10th Ed. (1983) p.402, Rahway: Merck & Co. Cytisine is also teratogenic.{{Cite book |title=Handbook of Natural Toxins: Toxicology of Plant and Fungal Compounds |vauthors=Keeler RF |publisher=CRC Press |page=43}}
Māmane (Sophora chrysophylla) can contain amounts of cytisine that are lethal to most animals. The palila (Loxioides bailleui, a bird), Uresiphita polygonalis virescens and Cydia species (moths), and possibly sheep and goats are not affected by the toxin for various reasons, and consume māmane, or parts of it, as food. U. p. virescens caterpillars are possibly able to sequester the cytisine to give themselves protection from predation; they have aposematic coloration which would warn off potential predators.{{Cite journal |vauthors=Banko PC, Cipollini ML, Breton GW, Paulk E, Wink M, Izhaki I |date=July 2002 |title=Seed chemistry of Sophora chrysophylla (mamane) in relation to diet of specialist avian seed predator Loxioides bailleui (palila) in Hawaii |url=http://www.uni-heidelberg.de/institute/fak14/ipmb/phazb/pdf-files/2002%20Pdf.Pubwink/1.2002.pdf |url-status=dead |journal=Journal of Chemical Ecology |volume=28 |issue=7 |pages=1393–1410 |bibcode=2002JCEco..28.1393B |doi=10.1023/A:1016248502927 |pmid=12199503 |s2cid=7064787 |archive-url=https://web.archive.org/web/20121221071323/http://www.uni-heidelberg.de/institute/fak14/ipmb/phazb/pdf-files/2002%20Pdf.Pubwink/1.2002.pdf |archive-date=21 December 2012 |access-date=4 May 2007}}
References
{{Reflist}}
External links
{{Commons category}}
- {{Cite web |title=Cytisinicline |url=https://druginfo.nlm.nih.gov/drugportal/name/cytisinicline |website=Drug Information Portal |publisher=U.S. National Library of Medicine}}
{{Stimulants}}
{{Antiaddictives}}
{{Nicotinic acetylcholine receptor modulators}}
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Category:Alkaloids found in Fabaceae
Category:Bridged heterocyclic compounds
Category:Nitrogen heterocycles