Cytisine

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Structural formula
Structure of (-) - cytisine
General
Surname Cytisine
other names

(1 R , 5 S ) -1,2,3,4,5,6-hexahydro-1,5-methano-8 H -pyrido [1,2- a ] diazocin-8-one ( IUPAC )

Molecular formula C 11 H 14 N 2 O
External identifiers / databases
CAS number 485-35-8
EC number 207-616-0
ECHA InfoCard 100.006.924
PubChem 10235
ChemSpider 9818
DrugBank DB09028
Wikidata Q417343
Drug information
ATC code

N07 BA

properties
Molar mass 190.24 g · mol -1
Physical state

firmly

Melting point

154-156 ° C

boiling point

218 ° C (2.7 h Pa )

solubility

good in water (439 g l −1 at 16 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
06 - Toxic or very toxic

danger

H and P phrases H: 301-315-319-335
P: 261-301 + 310-305 + 351 + 338
Toxicological data
  • 3 mg kg −1 ( LD Locat , sc injection )
  • 4 mg kg −1 ( LD Lodog , sc injection )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Cytisine is a toxic phytochemical from golden rain and belongs to the group of quinolizidine alkaloids. Its effect is similar to that of nicotine , as both substances interact with the same receptors in the brain.

Cytisine does not cause intoxication .

Occurrence

Golden rain inflorescence

Cytisine is the main alkaloid of the golden rain, but this only applies to the seeds and other parts of dormant growth. The content in the seeds is up to 3 percent.

Extraction and presentation

Cytisine can be synthesized from dinicotinic acid .

Medical application

Cytisine has a stimulating effect on nicotinic acetylcholine receptors and thus has an effect similar to that of nicotine. In the First World War, for example, leaves of the golden rain containing cytisine were used as a tobacco substitute. However, the cytisine has no addictive effect. It has been marketed in Bulgaria as a smoking cessation agent under the brand name Tabex since 1964 . In the years 1964 to 1989 it was also available in the Eastern Bloc for smoking cessation. Due to the Cold War, it was never approved in the western states. Today, apart from Bulgaria, cytisine is still used in Poland under various brand names, and since March 2018 it has also been approved as Asmoken in Austria.

There is a cross tolerance to nicotine.

Cytisine is the herbal model for the synthetic varenicline , which is approved in the USA under the brand name Chantix and has also been marketed in Europe under the name Champix since October 2006 . According to studies from 2011 and 2014, Tabex has a better effect than varenicline. According to the 2014 report in the Ärzteblatt , approval in the rest of Europe is not expected.

In its effect, cytisine is similar to other acetylcholine receptor agonists such as the nicotine of tobacco , anatoxin A of some cyanobacteria , epibatidine of the poison dart frogs and arecoline of the betel nuts .

Occurrence

Analytics

The qualitative and quantitative determination of cytisine is possible after appropriate sample preparation in blood as well as in plasma samples and in urine samples by coupling the HPLC with the mass spectrometry .

Web links

Individual evidence

  1. a b c data sheet cytisine (PDF) from Merck , accessed on December 14, 2010.
  2. a b Data sheet Cytisine from Sigma-Aldrich , accessed on March 23, 2011 ( PDF ).
  3. ^ A b Rudolf Hansel, Konstantin Keller, Horst Rimpler, Georg Schneider: Hager's Handbook of Pharmaceutical Practice Drugs E-O . Springer-Verlag, 2013, ISBN 978-3-642-57993-6 , pp. 628 ( limited preview in Google Book search).
  4. T. Dingermann, K. Hiller, G. Schneider, I. Zündorf: Schneider drug drugs . 5th edition, Elsevier 2004, ISBN 3-8274-1481-4 , p. 441.
  5. Tse-Lok Ho: Symmetry A Basis for Synthesis Design . John Wiley & Sons, 1995, ISBN 978-0-471-57376-0 , pp. 472 ( limited preview in Google Book search).
  6. C. Griebel: The microscopic examination of tea and tobacco substitutes. Message from the state food research institute in Berlin . In: Journal for the investigation of food and luxury goods as well as everyday objects, issue 9/10 from May 15, 1920. doi : 10.1007 / BF02125945
  7. Smoking cessation with cytisine- containing Tabex tablets . Reprint from The German Health System. 1968 (PDF; 1.9 MB).
  8. G. Habermehl, P. Ziemer: Central European poisonous plants and their active ingredients. 2nd edition, Springer-Verlag 1999, p. 95 f.
  9. Cytisine: Evidence-based smoking cessation with no prospect of approval , Ärzteblatt, December 2014.
  10. I. Yamamoto, JE Casida: Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor . Springer Science & Business Media, July 1, 1999, ISBN 978-4-431-70213-9 .
  11. R. Aráoz, J. Molgó, N. Tandeau de Marsac: Neurotoxic cyanobacterial toxins. In: Toxicon . Volume 56, Number 5, October 2010, pp. 813-828, doi : 10.1016 / j.toxicon.2009.07.036 , PMID 19660486 (review).
  12. BT Green, ST Lee, KD Welch, JA Pfister, KE Panter: Fetal muscle-type nicotinic acetylcholine receptor activation in TE-671 cells and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid coniine. In: The Journal of pharmacology and experimental therapeutics. Volume 344, Number 1, January 2013, pp. 295-307, doi : 10.1124 / jpet.112.199588 , PMID 23086230 .
  13. V. Gerzanich, X. Peng, F. Wang, G. Wells, R. Anand, S. Fletcher, J. Lindstrom: Comparative pharmacology of epibatidine: a potent agonist for neuronal nicotinic acetylcholine receptors. In: Molecular pharmacology. Volume 48, Number 4, October 1995, pp. 774-782, PMID 7476906 .
  14. KC Raffaele, A. Berardi, PP Morris, S. Asthana, JV Haxby, MB Schapiro, SI Rapoport, TT Soncrant: Effects of acute infusion of the muscarinic cholinergic agonist arecoline on verbal memory and visuo-spatial function in dementia of the Alzheimer type. In: Progress in neuro-psychopharmacology & biological psychiatry. Volume 15, Number 5, 1991, pp. 643-648, PMID 1956992 .
  15. Carlier J, Guitton J, Romeuf L, Bévalot F, Boyer B, Fanton L, Gaillard Y: Screening approach by ultra-high performance liquid chromatography-tandem mass spectrometry for the blood quantification of thirty-four toxic principles of plant origin. Application to forensic toxicology. , J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Jan 15; 975: 65-76, PMID 25438245
  16. Jeong SH, Newcombe D, Sheridan J, Tingle M: Pharmacokinetics of cytisine, an α4 β2 nicotinic receptor partial agonist, in healthy smokers following a single dose. , Drug Test Anal. 2015 Jun; 7 (6): 475-82, PMID 25231024