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Identification
NameCytisine
Accession NumberDB09028
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionCytisine is an alkaloid that is found naturally in several plant genera such as Laburnum and Cytisus of the family Fabaceae. Recent studies have shown it to be a more effective and significantly more affordable smoking cessation treatment than nicotine replacement therapy. Also known as baptitoxine or sophorine, cytisine has been used as a smoking cessation treatment since 1964, and is relatively unknown in regions outside of central and Eastern Europe. Cytisine is a partial nicotinic acetylcholine agonist with a half-life of 4.8 hours. Recent Phase III clinical trials using Tabex (a brand of Cytisine marketed by Sopharma AD) have shown similar efficacy to varenicline, but at a fraction of the cost.
Structure
Thumb
Synonyms
(1R,5S)-1,2,3,4,5,6-Hexahydro-1,5-methano-8H-pyrido[1,2a][1,5]diazocin-8-one
Baptitoxine
Sophorine
Ulexin
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TabexSopharma AD
Brand mixturesNot Available
SaltsNot Available
Categories
UNII53S5U404NU
CAS number485-35-8
WeightAverage: 190.2417
Monoisotopic: 190.11061308
Chemical FormulaC11H14N2O
InChI KeyANJTVLIZGCUXLD-DTWKUNHWSA-N
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
IUPAC Name
(1R,9S)-7,11-diazatricyclo[7.3.1.0²,⁷]trideca-2,4-dien-6-one
SMILES
O=C1C=CC=C2[[email protected]]3CNC[[email protected]](C3)CN12
Pharmacology
IndicationIndicated for use in smoking cessation.
Structured Indications Not Available
PharmacodynamicsVarious models have been run where the affinity of nAChR agonists to the receptor subtype are tested to help identify the molecules, groups and steric conformation that are vital to greater affinity. By using a nAChR muscle receptor subtype (α1)2β1δγ model the following results were obtained: anatoxin > epibatidine > acetylcholine > DMPP >> CYTISINE > pyrantel > nicotine > coniine > tubocurare > lobeline, where anatoxin had the highest activity efficacy and tubocurare the lowest. Acetylcholine on the other hand induced a much longer opening time of the receptor though anatoxin is more potent. The results suggest that anatoxin derivatives would be helpful in understanding structure-activity relationships (SAR) for muscle nAChRs (Cooper et al., 1996).
Mechanism of actionCytisine is a low efficacy partial agonist of ⍺4-β2 nicotinic acetylcholine receptors. These which are believed to be central to the effect of nicotine (NIC) on the reward pathway and facilitate addiction. Cytisine reduces the effects of NIC on dopamine release in the mesolimbic system when given alone, while simultaneously attenuating NIC withdrawal symptoms that accompany cessation attempts.
TargetKindPharmacological actionActionsOrganismUniProt ID
Neuronal acetylcholine receptor subunit alpha-4Proteinunknown
agonist
HumanP43681 details
Neuronal acetylcholine receptor subunit alpha-7Proteinunknown
agonist
HumanP36544 details
Neuronal acetylcholine receptor subunit alpha-3Proteinunknown
agonist
HumanP32297 details
Neuronal acetylcholine receptor subunit alpha-6Proteinunknown
agonist
HumanQ15825 details
Related Articles
AbsorptionNot Available
Volume of distribution

Oral: 6.2 l/kg Oral (5 mg/kg; tested in rabbits).

Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life4.8 hours.
Clearance

Renal: 43 mL/min.

ToxicityThe therapeutic index of cytisine is wide. -Large doses can interfere with breathing and cause death. From MSDS: orl-mus LD50:101 mg/kg ipr-mus LD50:8550 ug/kg ivn-mus LD50:1730 ug/kg scu-rat LD50:8750 ug/kg
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis Reference

ORGANIC SYNTHESES, 2006, 83, 141. “Synthesis of ()-(1R,@S,9S)-11-Methyl-7,11-Diazatricyclo[7.3.1.02.7]tridecane, a ()sparteine surrogate,” DOI: 10.15227/orgsyn.083.0141

General References
  1. Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C: Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014 Dec 18;371(25):2353-62. doi: 10.1056/NEJMoa1407764. [PubMed:25517706 ]
  2. Houlihan LM, Slater Y, Guerra DL, Peng JH, Kuo YP, Lukas RJ, Cassels BK, Bermudez I: Activity of cytisine and its brominated isosteres on recombinant human alpha7, alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors. J Neurochem. 2001 Sep;78(5):1029-43. [PubMed:11553677 ]
  3. Tutka P, Zatonski W: Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy. Pharmacol Rep. 2006 Nov-Dec;58(6):777-98. [PubMed:17220536 ]
  4. Cooper JC, Gutbrod O, Witzemann V, Methfessel C: Pharmacology of the nicotinic acetylcholine receptor from fetal rat muscle expressed in Xenopus oocytes. Eur J Pharmacol. 1996 Aug 15;309(3):287-98. [PubMed:8874153 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (38.7 KB)
ADMET
Predicted ADMET featuresNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point152-153Not Available
boiling point218Not Available
Predicted Properties
PropertyValueSource
Water Solubility8.14 mg/mLALOGPS
logP1.06ALOGPS
logP-0.28ChemAxon
logS-1.4ALOGPS
pKa (Strongest Basic)9.82ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area32.34 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity56.93 m3·mol-1ChemAxon
Polarizability20.35 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cytisine and derivatives. These are lupin alkaloids with a structure based on the cytisine skeleton, which is a tetracyclic ketone containing fused pyridine and piperidine rings that form pyrido[1,2a][1,5]diazocin-8-one.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassLupin alkaloids
Sub ClassCytisine and derivatives
Direct ParentCytisine and derivatives
Alternative Parents
Substituents
  • Cytisine
  • Aralkylamine
  • Pyridinone
  • Pyridine
  • Piperidine
  • Heteroaromatic compound
  • Lactam
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Ligand-gated ion channel activity
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
Gene Name:
CHRNA4
Uniprot ID:
P43681
Molecular Weight:
69956.47 Da
References
  1. Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C: Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014 Dec 18;371(25):2353-62. doi: 10.1056/NEJMoa1407764. [PubMed:25517706 ]
  2. Houlihan LM, Slater Y, Guerra DL, Peng JH, Kuo YP, Lukas RJ, Cassels BK, Bermudez I: Activity of cytisine and its brominated isosteres on recombinant human alpha7, alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors. J Neurochem. 2001 Sep;78(5):1029-43. [PubMed:11553677 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Toxic substance binding
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin.
Gene Name:
CHRNA7
Uniprot ID:
P36544
Molecular Weight:
56448.925 Da
References
  1. Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C: Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014 Dec 18;371(25):2353-62. doi: 10.1056/NEJMoa1407764. [PubMed:25517706 ]
  2. Houlihan LM, Slater Y, Guerra DL, Peng JH, Kuo YP, Lukas RJ, Cassels BK, Bermudez I: Activity of cytisine and its brominated isosteres on recombinant human alpha7, alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors. J Neurochem. 2001 Sep;78(5):1029-43. [PubMed:11553677 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Ligand-gated ion channel activity
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name:
CHRNA3
Uniprot ID:
P32297
Molecular Weight:
57479.54 Da
References
  1. Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C: Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014 Dec 18;371(25):2353-62. doi: 10.1056/NEJMoa1407764. [PubMed:25517706 ]
  2. Houlihan LM, Slater Y, Guerra DL, Peng JH, Kuo YP, Lukas RJ, Cassels BK, Bermudez I: Activity of cytisine and its brominated isosteres on recombinant human alpha7, alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors. J Neurochem. 2001 Sep;78(5):1029-43. [PubMed:11553677 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Acetylcholine-activated cation-selective channel activity
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name:
CHRNA6
Uniprot ID:
Q15825
Molecular Weight:
56897.745 Da
References
  1. Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C: Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014 Dec 18;371(25):2353-62. doi: 10.1056/NEJMoa1407764. [PubMed:25517706 ]
  2. Houlihan LM, Slater Y, Guerra DL, Peng JH, Kuo YP, Lukas RJ, Cassels BK, Bermudez I: Activity of cytisine and its brominated isosteres on recombinant human alpha7, alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors. J Neurochem. 2001 Sep;78(5):1029-43. [PubMed:11553677 ]
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Drug created on December 19, 2014 09:51 / Updated on August 17, 2016 12:24