Varenicline

Structural formula
General
Non-proprietary name	Varenicline
other names	(6 R , 10 S ) -7,8,9,10-tetrahydro-6,10-methano-6 H -pyrazino [2,3- h ] - [3] benzazepine ( IUPAC ); Vareniclinum ( Latin );
Molecular formula	C 13 H 13 N 3
External identifiers / databases
PubChem	5310966
DrugBank	DB01273
Wikidata	Q411330
Drug information
ATC code	N07 BA03
Drug class	Means of smoking cessation
properties
Molar mass	211.26 g · mol -1
solubility	soluble in DMSO
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Varenicline tartrate Caution
H and P phrases	H: 400
	P: 273
Toxicological data	> 2000 mg kg −1 ( LD 50 , rat , transdermal , varenicline tartrate)
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Varenicline is a drug that is used to help you quit smoking . Its action unfolds this drug as well as the structurally similar cytisine , an alkaloid of the laburnum , the receptors of nicotine ( nicotine receptors ). It is approved as a tartrate in the United States under the brand name Chantix . The drug has also been approved in Europe since October 2006 and is marketed under the name Champix . The pharmaceutical company Pfizer has been marketing the active ingredient in Germany since March 1, 2007.

pharmacology

Mechanism of action

Varenicline is a partial agonist at nicotine receptors of the subtype α4β2, which seems to be partly responsible for an addictive effect of nicotine. As a partial agonist, it partially stimulates the receptor on the one hand, which minimizes the withdrawal symptoms of smoking cessation, and on the other hand, it inhibits the effects of externally added nicotine, which would render additional smoking ineffective.

Side effects

When using varenicline, nausea , headache , vomiting , gas and sleep disorders can occur frequently. Some patients experience somnolence (drowsiness) and vertigo (dizziness), which can make it difficult to drive or use machines. Abnormal dreaming , taste disorders and other side effects have also been reported. Cases of depression , suicidal ideation and suicide , aggressiveness and abnormal behavior with varenicline have been documented. Worldwide, there were 39 completed suicides in 2008 among patients treated with varenicline, of which, however, as the American FDA determined, 50% had a psychiatric history. The FDA has therefore issued a conspicuous warning. A cohort study in England found no difference in the probability of occurrence of depression, suicidal ideation or attempted suicide, and suicide after treatment with varenicline, bupropion and nicotine substitutes . A meta-analysis from 2014 contradicts the risk of suicide.

In 2006 an increase in heart attacks and cardiac arrhythmias was suspected with varenicline. This was also contradicted in a meta-analysis in 2014.

Interactions

Varenicline can affect the way some drugs work:

Insulin (used to treat diabetes mellitus)
Theophylline (used to treat breathing problems such as bronchial asthma)
Warfarin (medicine to thin the blood)
Cimetidine (for acid-related stomach problems)

In addition, the agent can in individual cases increase the effect of alcohol. In some cases, the FDA's Adverse Event Reporting System (FAERS) database shows that patients exhibited decreased tolerance to alcohol with increased levels of drunkenness, aggressive or unusual behavior.

chemistry

synthesis

Varenicline can be produced from benzazepine in a three-step synthesis . This synthesis takes place via dinitration of the aromatic system , reduction of the nitro groups and condensation with glyoxal .

literature

J. Foulds: The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. In: International Journal of Clinical Practice. 60, 2006, p. 571, doi : 10.1111 / j.1368-5031.2006.00955.x .
TJ Moore, CD Furberg, J. Glenmullen, JT Maltsberger, S. Singh: Suicidal behavior and depression in smoking cessation treatments. In: PloS one. Volume 6, number 11, 2011, p. E27016, doi : 10.1371 / journal.pone.0027016 . PMID 22073240 . PMC 3206890 (free full text).

Web links

Critical evaluation
European Public Assessment Report (EPAR) - Champix (PDF file; 105 kB)
Pharmacy smoking advice: Varenicline

Individual evidence

↑ ^a ^b ^c ^d data sheet Varenicline tartrate from Sigma-Aldrich , accessed on April 28, 2014 ( PDF ).
↑ Specialist information Champix.
^ FDA: Early Communication About an Ongoing Safety Review Varenicline , November 20, 2007.
↑ ^a ^b P. Christalla, M. Dewenter, A. El-Armouche: [Effectiveness and safety of varenicline for smoking cessation]. In: German Medical Weekly (1946). Volume 137, number 18, May 2012, pp. 940-944, doi : 10.1055 / s-0032-1304895 . PMID 22492478 .
↑ FDA drug safety newsletter , 2009, Vol. 2, No. 1 (PDF; 778 kB).
^ JR Hughes: Varenicline as a Cause of Suicidal Outcomes. . In: Nicotine & tobacco research: official journal of the Society for Research on Nicotine and Tobacco . January 8, 2015. doi : 10.1093 / ntr / ntu275 . PMID 25572451 .
^ Varenicline: new drug. Smoking cessation: no better than nicotine. In: Prescrire international. Volume 15, Number 86, December 2006, pp. 210-212, PMID 17165237 .
↑ EJ Mills, K Thorlund, S Eapen, P Wu, JJ Prochaska: Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis. . In: Circulation . 129, No. 1, January 7, 2014, pp. 28-41. doi : 10.1161 / circulationaha.113.003961 . PMID 24323793 .
^ Interactions of varenicline. Retrieved June 28, 2017 .
↑ JW Coe, PR Brooks, MG Vetelino, MC Wirtz, EP Arnold, J. Huang, SB Sands, TI Davis, LA Lebel, CB Fox, A. Shrikhande, JH Heym, E. Schaeffer, H. Rollema, Y. Lu , RS Mansbach, LK Chambers, CC Rovetti, DW Schulz, FD Tingley, BT O'Neill: Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. In: Journal of medicinal chemistry. Volume 48, Number 10, May 2005, pp. 3474-3477, doi : 10.1021 / jm050069n . PMID 15887955 .

[Sigma-1] ta sheet Varenicline tartrate from Sigma-Aldrich , accessed on April 28, 2014 ( PDF ).

[2] Specialist information Champix.

[3] FDA: Early Communication About an Ongoing Safety Review Varenicline , November 20, 2007.

[Christalla-4] P. Christalla, M. Dewenter, A. El-Armouche: [Effectiveness and safety of varenicline for smoking cessation]. In: German Medical Weekly (1946). Volume 137, number 18, May 2012, pp. 940-944, doi : 10.1055 / s-0032-1304895 . PMID 22492478 .

[5] FDA drug safety newsletter , 2009, Vol. 2, No. 1 (PDF; 778 kB).

[6] JR Hughes: Varenicline as a Cause of Suicidal Outcomes. . In: Nicotine & tobacco research: official journal of the Society for Research on Nicotine and Tobacco . January 8, 2015. doi : 10.1093 / ntr / ntu275 . PMID 25572451 .

[7] Varenicline: new drug. Smoking cessation: no better than nicotine. In: Prescrire international. Volume 15, Number 86, December 2006, pp. 210-212, PMID 17165237 .

[8] EJ Mills, K Thorlund, S Eapen, P Wu, JJ Prochaska: Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis. . In: Circulation . 129, No. 1, January 7, 2014, pp. 28-41. doi : 10.1161 / circulationaha.113.003961 . PMID 24323793 .

[9] Interactions of varenicline. Retrieved June 28, 2017 .

[10] JW Coe, PR Brooks, MG Vetelino, MC Wirtz, EP Arnold, J. Huang, SB Sands, TI Davis, LA Lebel, CB Fox, A. Shrikhande, JH Heym, E. Schaeffer, H. Rollema, Y. Lu , RS Mansbach, LK Chambers, CC Rovetti, DW Schulz, FD Tingley, BT O'Neill: Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. In: Journal of medicinal chemistry. Volume 48, Number 10, May 2005, pp. 3474-3477, doi : 10.1021 / jm050069n . PMID 15887955 .