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VARENICLINE

Varenicline chemical structure
Varenicline
Systematic (IUPAC) name
7,8,9,10-tetrahydro-6,10-methano-
6H-pyrazino(2,3-h)(3)benzazepine
Identifiers
CAS number 249296-44-4
375815-87-5
ATC code N07BA03
PubChem 170361
Chemical data
Formula C13H13N3 
Mol. weight 211.267
SMILES C1C2CNCC1C3=CC4=NC=CN=
C4C=C23
Pharmacokinetic data
Bioavailability  ?
Protein binding <20%
Metabolism limited
Half life 24 hours
Excretion renal (81-92%)
Therapeutic considerations
Pregnancy cat.

?
Legal status

RX/POM
Routes oral

Varenicline (Chantix®, Pfizer, usually as varenicline tartrate) is a prescription medication used to treat smoking addiction. By acting similarly to nicotine on the brain it reduces cravings for cigarettes and other tobacco products and may assist some patients in smoking cessation. In May, 2006, it was approved for sale in the United States. On August 1, 2006, Pfizer announced that Chantix is now available for sale in the United States. It has not yet been approved for sale in any other country.

Contents

Use and dosing

Varenicline is "indicated" for (suggested for use in) smoking cessation. It is an alternative to bupropion (Zyban) and nicotine replacement therapy (NRT), such as nicotine patches.

Varenicline is available as 0.5 mg and 1 mg tablets. Standard dosing is 1 mg twice daily. The FDA has approved it use in for twelve weeks; if smoking cessation has been achieved it may be continued for another twelve weeks.[1]

Mechanism of action

Varenicline is a partial agonist of the α4β2 subtype of the nicotinic acetylcholine receptor. In addition it acts on α3β4 and weakly on α3β2 and α6-containing receptors. A full agonism was displayed on α7-receptors.[2]

Pharmacokinetics

Most of the active compound is excreted renally (81%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.[3]

Side-effects

Side-effects include[1]:

History

Varenicline was selected from a large number of compounds that showed affinity to the α4β2 nicotinic receptor.[4] It derives chemically from cytisine.

Varenicline received a "priority review" by the U.S. Food and Drug Administration in February 2006, shortening the usual 10-month review period to 6 months because of its demonstrated effectiveness in clinical trials.[5] The agency's approval of the drug came on May 11, 2006.[1]

References

  1. ^ a b c U.S. Food and Drug Administration. FDA Approves Novel Medication for Smoking Cessation. Press release, 11 May 2006.
  2. ^ Mihalak KB, Carroll FI, Luetje CW. Varenicline is a partial agonist at α4β2 and a full agonist at α7 neuronal nicotinic receptors. Mol Pharmacol 2006 in press. PMID 16766716.
  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;34:121-30. PMID 16221753.
  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;48:3474-7. PMID 15887955.
  5. ^ Kuehn BM. FDA speeds smoking cessation drug review. JAMA 2006;295:614. PMID 16467225.

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