Identification
- Summary
Cytisine is an alkaloid with partial agonist activity at the α4β2 nicotinic acetylcholine receptor used to aid smoking cessation.
- Generic Name
- Cytisine
- DrugBank Accession Number
- DB09028
- Background
Cytisine is an alkaloid naturally derived from the Fabaceae family of plants including the genera Laburnum and Cytisus. 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.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Cytisine (DB09028)
- Weight
- Average: 190.2417
Monoisotopic: 190.11061308 - Chemical Formula
- C11H14N2O
- 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
Pharmacology
- Indication
Indicated for use in smoking cessation.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Various 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 action
Cytisine 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.
Target Actions Organism UNeuronal acetylcholine receptor subunit alpha-4 agonistHumans UNeuronal acetylcholine receptor subunit alpha-7 agonistHumans UNeuronal acetylcholine receptor subunit alpha-3 agonistHumans UNeuronal acetylcholine receptor subunit alpha-6 agonistHumans UNeuronal acetylcholine receptor subunit beta-2 partial agonistHumans - Absorption
Not Available
- Volume of distribution
Oral: 6.2 l/kg Oral (5 mg/kg; tested in rabbits).
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
4.8 hours.
- Clearance
Renal: 43 mL/min.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The 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
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Tabex (Sopharma AD)
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Lupin alkaloids
- Sub Class
- Cytisine and derivatives
- Direct Parent
- Cytisine and derivatives
- Alternative Parents
- Pyridinones / Aralkylamines / Piperidines / Heteroaromatic compounds / Lactams / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organic oxides show 1 more
- Substituents
- Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Cytisine / Heteroaromatic compound / Hydrocarbon derivative / Lactam / Organic nitrogen compound / Organic oxide show 10 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organic heterotricyclic compound, alkaloid, secondary amino compound, bridged compound, lactam (CHEBI:4055)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 53S5U404NU
- CAS number
- 485-35-8
- InChI Key
- ANJTVLIZGCUXLD-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[7.3.1.0^{2,7}]trideca-2,4-dien-6-one
- SMILES
- O=C1C=CC=C2[C@H]3CNC[C@H](C3)CN12
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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- External Links
- KEGG Drug
- D07770
- KEGG Compound
- C10763
- PubChem Compound
- 10235
- PubChem Substance
- 310264982
- ChemSpider
- 9818
- BindingDB
- 50143282
- 1723152
- ChEBI
- 4055
- ChEMBL
- CHEMBL497939
- ZINC
- ZINC000001599730
- PDBe Ligand
- C5E
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Cytisine
- PDB Entries
- 4bqt / 5syo
- MSDS
- Download (38.7 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Smoking, Cessation 1 3 Completed Treatment Smoking, Cessation 3 3 Recruiting Treatment Nicotine Addiction 1 3 Recruiting Treatment Smoking, Cessation 1 2 Active Not Recruiting Prevention Diet Modification / Inflammation / Malignant Lung Neoplasm / Physical Activities / Smoking, Cessation 1 2 Completed Treatment E Cig Use / Vaping 1 2 Completed Treatment Smoking, Cessation 1 2, 3 Completed Treatment Alcohol Use / Human Immunodeficiency Virus (HIV) Infections / Smoking 1 2, 3 Not Yet Recruiting Treatment Smoking (Tobacco) Addiction / Smoking, Cessation 1 1 Completed Treatment Smoking, Cessation 4
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Tablet 1.5 MG - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 152-153 Not Available boiling point (°C) 218 Not Available - Predicted Properties
Property Value Source Water Solubility 8.14 mg/mL ALOGPS logP 1.06 ALOGPS logP -0.28 Chemaxon logS -1.4 ALOGPS pKa (Strongest Basic) 9.82 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 32.34 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 56.93 m3·mol-1 Chemaxon Polarizability 20.35 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
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- Kind
- Protein
- Organism
- Humans
- 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 permeabl...
- Gene Name
- CHRNA4
- Uniprot ID
- P43681
- Uniprot Name
- Neuronal acetylcholine receptor subunit alpha-4
- Molecular Weight
- 69956.47 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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 cha...
- Gene Name
- CHRNA7
- Uniprot ID
- P36544
- Uniprot Name
- Neuronal acetylcholine receptor subunit alpha-7
- Molecular Weight
- 56448.925 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- Uniprot Name
- Neuronal acetylcholine receptor subunit alpha-3
- Molecular Weight
- 57479.54 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- Uniprot Name
- Neuronal acetylcholine receptor subunit alpha-6
- Molecular Weight
- 56897.745 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Partial 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 permeabl...
- Gene Name
- CHRNB2
- Uniprot ID
- P17787
- Uniprot Name
- Neuronal acetylcholine receptor subunit beta-2
- Molecular Weight
- 57018.575 Da
References
- Rollema H, Shrikhande A, Ward KM, Tingley FD 3rd, Coe JW, O'Neill BT, Tseng E, Wang EQ, Mather RJ, Hurst RS, Williams KE, de Vries M, Cremers T, Bertrand S, Bertrand D: Pre-clinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence. Br J Pharmacol. 2010 May;160(2):334-45. doi: 10.1111/j.1476-5381.2010.00682.x. Epub 2010 Mar 22. [Article]
Drug created at December 19, 2014 16:51 / Updated at May 27, 2021 02:57