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Identification
Name Varenicline
Accession Number DB01273
Type small molecule
Groups approved
Description

Varenicline is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. Specifically, varenicline is a partial agonist of the alpha4/beta2 subtype of the nicotinic acetylcholine receptor. In addition it acts on alpha3/beta4 and weakly on alpha3beta2 and alpha6-containing receptors. A full agonism was displayed on alpha7-receptors.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
CP-526,555
Varenicline tartrate
Salts Not Available
Brand names
Name Company
Champix
Chantix
Brand mixtures Not Available
Categories
  • Nicotinic Agonists
CAS number 249296-44-4
Weight Average: 211.2624
Monoisotopic: 211.110947431
Chemical Formula C13H13N3
InChI Key InChIKey=JQSHBVHOMNKWFT-DTORHVGOSA-N
InChI
InChI=1S/C13H13N3/c1-2-16-13-5-11-9-3-8(6-14-7-9)10(11)4-12(13)15-1/h1-2,4-5,8-9,14H,3,6-7H2/t8-,9+
Plain Text
IUPAC Name
(1R,12S)-5,8,14-triazatetracyclo[10.3.1.0^{2,11}.0^{4,9}]hexadeca-2(11),3,5,7,9-pentaene
SMILES
[H][C@]12C[C@]([H])(CNC1)C1=CC3=NC=CN=C3C=C21
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpiperidines
  • Benzazepines
Substructures
  • Indanes
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Phenylpiperidines
  • Pyrazines
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzazepines
  • Quinoxalines
  • Piperidines
Pharmacology
Indication For use as an aid in smoking cessation.
Pharmacodynamics Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain.
Mechanism of action Varenicline is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor partial agonist. The drug shows high selectiviyty for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms.
Absorption Not Available
Volume of distribution Not Available
Protein binding Less than 20%.
Metabolism
Metabolism is limited (<10%). Most of the active compound is excreted renally (81%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.
Route of elimination Varenicline undergoes minimal metabolism, with 92% excreted unchanged in the urine. Renal elimination of varenicline is primarily through glomerular filtration along with active tubular secretion possibly via the organic cation transporter, OCT2.
Half life The elimination half-life of varenicline is approximately 24 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pfizer inc
Packagers
Dosage forms
Form Route Strength
Tablet, film coated Oral
Prices
Unit description Cost Unit
Chantix Continuing Month Pak 56 1 mg tablet Disp Pack 148.5 USD disp
Chantix Starting Month Pak 0.5 mg X 11, 1 mg X 42 Disp Pack 148.5 USD disp
Chantix 1 mg tablet 2.61 USD tablet
Chantix 0.5 mg tablet 2.56 USD tablet
Chantix 1 mg cont month pak 2.56 USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 7265119 2002-08-03 2022-08-03
United States 6410550 2000-05-10 2020-05-10
Canada 2525874 2007-11-27 2024-05-07
Canada 2316921 2004-12-07 2018-11-13
Properties
State solid
Experimental Properties
Property Value Source
logP 0.9 Not Available
Predicted Properties
Property Value Source
water solubility 8.77e-02 g/l ALOGPS
logP 1.39 ALOGPS
logP 1.01 ChemAxon
logS -3.4 ALOGPS
pKa (strongest basic) 9.73 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 37.81 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 61.3 ChemAxon
polarizability 23.12 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR: Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. Pubmed
  2. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. Pubmed
  3. Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O’Connell TN, Zandi KS, Miller S, Coe JW: Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos. 2006 Jan;34(1):121-30. Epub 2005 Oct 12. Pubmed
  4. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley FD 3rd, O’Neill BT: Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005 May 19;48(10):3474-7. Pubmed
  5. Kuehn BM: FDA speeds smoking cessation drug review. JAMA. 2006 Feb 8;295(6):614. Pubmed
External Links
Resource Link
PubChem Compound 5310966 Link_out
PubChem Substance 46505502 Link_out
ChemSpider 4470510 Link_out
Therapeutic Targets Database DAP001535 Link_out
PharmGKB PA164781343 Link_out
RxList http://www.rxlist.com/cgi/generic/chantix.htm Link_out
Drugs.com http://www.drugs.com/cdi/varenicline.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Varenicline Link_out
ATC Codes
  • N07BA03
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (334 KB)
MSDS Not Available
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Neuronal acetylcholine receptor subunit alpha-4

Pharmacological action: yes
Actions: partial agonist

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

Organism class: human
UniProt ID: P43681 Link_out
Gene: CHRNA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nakamura M, Oshima A, Fujimoto Y, Maruyama N, Ishibashi T, Reeves KR: Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. Clin Ther. 2007 Jun;29(6):1040-56. Pubmed
  2. McColl S, Burstein A, Reeves K, Billing Jr C, Stolar M, Sellers E: Human Abuse Liability of the Smoking Cessation Drug Varenicline in Smokers and Nonsmokers. Clin Pharmacol Ther. 2008 Feb 20;. Pubmed
  3. Rollema H, Coe JW, Chambers LK, Hurst RS, Stahl SM, Williams KE: Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation. Trends Pharmacol Sci. 2007 Jul;28(7):316-25. Epub 2007 Jun 18. Pubmed
  4. Steensland P, Simms JA, Holgate J, Richards JK, Bartlett SE: Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12518-23. Epub 2007 Jul 11. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Neuronal acetylcholine receptor subunit alpha-7

Pharmacological action: unknown
Actions: agonist

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

Organism class: human
UniProt ID: P36544 Link_out
Gene: CHRNA7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. Pubmed

3. Neuronal acetylcholine receptor subunit alpha-3

Pharmacological action: unknown
Actions: partial agonist

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

Organism class: human
UniProt ID: P32297 Link_out
Gene: CHRNA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. Pubmed

4. Neuronal acetylcholine receptor subunit alpha-6

Pharmacological action: unknown
Actions: partial agonist

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

Organism class: human
UniProt ID: Q15825 Link_out
Gene: CHRNA6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. Pubmed
Comments
Drug created on May 16, 2007 14:24 / Updated on February 08, 2013 16:20