Cytisinicline

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Not to be confused with cytosine, cysteine, cystine, cytidine, or cotinine.

Cytisinicline
Skeletal formula of cytisinicline
Ball-and-stick model of the cytisinicline molecule
Names
Preferred IUPAC name
(1R,5S)-1,2,3,4,5,6-Hexahydro-8H-1,5-methanopyrido[1,2-a][1,3]diazocin-8-one
Other names
Cytisine
Baptitoxine
Sophorine
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.006.924 Edit this at Wikidata
IUPHAR/BPS
PubChem CID
UNII
CompTox Dashboard (EPA)
InChI
  • InChI=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 checkY
    Key: ANJTVLIZGCUXLD-DTWKUNHWSA-N checkY
  • InChI=1/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
    Key: ANJTVLIZGCUXLD-DTWKUNHWBR
SMILES
  • O=C1/C=C\C=C2/N1C[C@@H]3CNC[C@H]2C3
Properties
Chemical formula
 C11H14N2O
Molar mass 190.24 g/mol
Melting point 152 to 153 °C (306 to 307 °F; 425 to 426 K)
Boiling point 218 °C (424 °F; 491 K) at 2 mmHg
Pharmacology
ATC code
 N07BA04 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Cytisinicline, also known as baptitoxine, cytisine, 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.[1] Although widely used for smoking cessation in Eastern Europe, cytisinicline remains relatively unknown beyond it.[citation needed] However, it has been found effective in several randomized clinical 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 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).[2]

Sources[]

Cytisinicline is extracted from the seeds of 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. Cytisinicline is also present in Gymnocladus of the subfamily Caesalpinioideae.

Uses[]

Smoking cessation[]

Cytisinicline 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.[3] It was first marketed in Bulgaria in 1964 and then became widely available in the then-Soviet Union.[4] In Poland, it is sold under the brand name Desmoxan, and it is also available in Canada under the brand name Cravv.[5][6]

Its molecular structure has some similarity to that of nicotine, and it has similar pharmacological effects. Like the smoking cessation aid varenicline, cytisinicline is a partial agonist of nicotinic acetylcholine receptors (nAChRs).[7] Cytisinicline has a short half-life of 4.8 hours,[8] 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.[9]

Cytisinicline is rapidly eliminated from the body.[medical citation needed]

In 2011, a randomized controlled trial with 740 patients found cytisinicline improved 12-month abstinence from nicotine from 2.4% with placebo to 8.4% with cytisinicline.[10] A 2013 meta-analysis of eight studies demonstrated that cytisinicline has similar effectiveness to varenicline but with substantially lower side effects.[11] A 2014 systematic review and economic evaluation concluded that cytisinicline was more likely to be cost-effective for smoking cessation than varenicline.[12]

Recreational[]

Plants containing cytisinicline, including the scotch broom and mescalbean, have also been used recreationally. Positive effects are reported to include a nicotine-like intoxication.[10]

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.[13]

Toxicity[]

Cytisinicline can interfere with breathing and cause death; LD50 i.v., in mice is about 2 mg/kg.[14] Cytisinicline is also teratogenic.[15]

Māmane (Sophora chrysophylla) can contain amounts of cytisinicline 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 use māmane, or parts thereof, as food. U. p. virescens caterpillars are possibly able to sequester the cytisinicline to give themselves protection from getting eaten; they have aposematic coloration which would warn off potential predators.[16]

References[]

  1. ^ a b Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, et al. (2014). "Cytisine versus Nicotine for Smoking Cessation". New England Journal of Medicine. 371 (25): 2353–62. doi:10.1056/nejmoa1407764. PMID 25517706.
  2. ^ 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". Addiction. 114 (5): 923–93. doi:10.1111/add.14541. PMID 30589984. S2CID 58621453.
  3. ^ Zatonski, Witold; Cedzynska, Magdalena; Tutka, Piotr; West, Robert (December 2006). "An uncontrolled trial of cytisine (Tabex) for smoking cessation". Tobacco Control. 15 (6): 481–484. doi:10.1136/tc.2006.016097. ISSN 0964-4563. PMC 2563682. PMID 17130378 – via NCBI.
  4. ^ "Old anti-smoking drug passes new test". Reuters. 28 September 2011. Retrieved 11 March 2022.
  5. ^ Prochaska, J. J.; Das, S.; Benowitz, N. L. (23 August 2013). "Cytisine, the world's oldest smoking cessation aid". BMJ. 347 (aug23 1): f5198–f5198. doi:10.1136/bmj.f5198. ISSN 1756-1833.
  6. ^ Zatoński, Witold; Janik-Koncewicz, Kinga; Stępnicka, Zuzanna; Zatońska, Katarzyna; Połtyn-Zaradna, Katarzyna; Herbeć, Aleksandra (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. ISSN 2450-5927.
  7. ^ Dallanoce C, Frigerio F, Martelli G, Grazioso G, Matera C, Pomè DY, et al. (2010). "Novel tricyclic Δ2-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. ISSN 0968-0896. PMID 20478710.
  8. ^ Jeong SH, Newcombe D, Sheridan J, Tingle M (June 2015). "Pharmacokinetics of cytisine, an α4β2 nicotinic receptor partial agonist, in healthy smokers following a single dose". Drug Testing and Analysis. 7 (6): 475–482. doi:10.1002/dta.1707. ISSN 1942-7611. PMID 25231024.
  9. ^ Reinberg S (17 December 2014). "Cheap Natural Compound May Help Smokers Quit. But cytisinicline isn't widely available, study authors note". WebMD. Retrieved 4 June 2021.
  10. ^ a b West R, Zatonski W, Cedzynska M, Lewandowska D, Pazik J, Aveyard P, Stapleton J (2011). "Placebo-Controlled Trial of Cytisine for Smoking Cessation". New England Journal of Medicine. 365 (13): 1193–1200. doi:10.1056/NEJMoa1102035. PMID 21991893.
  11. ^ Hajek P, McRobbie H, Myers K (25 February 2013). "Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis". Thorax. 68 (11): 1037–42. doi:10.1136/thoraxjnl-2012-203035. PMID 23404838.
  12. ^ Leaviss J, Sullivan W, Ren S, Everson-Hock E, Stevenson M, Stevens J, et al. (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. PMC 4780997. PMID 24831822.
  13. ^ "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.
  14. ^ The Merck Index, 10th Ed. (1983) p.402, Rahway: Merck & Co.
  15. ^ R. F. Keeler. Handbook of Natural Toxins: Toxicology of Plant and Fungal Compounds. CRC Press. p. 43.
  16. ^ Banko PC, Cipollini ML, Breton GW, Paulk E, Wink M, Izhaki I (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): 1393–410. doi:10.1023/A:1016248502927. PMID 12199503. S2CID 7064787. Archived from the original (PDF) on 21 December 2012. Retrieved 4 May 2007.

External links[]

  • "Cytisinicline". Drug Information Portal. U.S. National Library of Medicine.
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