U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C13H13N3.C4H6O6
Molecular Weight 361.3493
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VARENICLINE TARTRATE

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.C1[C@H]2CNC[C@@H]1C3=CC4=C(C=C23)N=CC=N4

InChI

InChIKey=TWYFGYXQSYOKLK-CYUSMAIQSA-N
InChI=1S/C13H13N3.C4H6O6/c1-2-16-13-5-11-9-3-8(6-14-7-9)10(11)4-12(13)15-1;5-1(3(7)8)2(6)4(9)10/h1-2,4-5,8-9,14H,3,6-7H2;1-2,5-6H,(H,7,8)(H,9,10)/t8-,9+;1-,2-/m.1/s1

HIDE SMILES / InChI

Molecular Formula C13H13N3
Molecular Weight 211.2624
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity NONE

Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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. 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. Varenicline is sold under the trade name Chantix and Champix, it is indicated for use as an aid to smoking cessation treatment.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.4 nM [Ki]
130.0 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
CHANTIX

Cmax

ValueDoseCo-administeredAnalytePopulation
6.38 ng/mL
1 mg single, oral
VARENICLINE plasma
Homo sapiens
5.7 ng/mL
1 mg single, oral
VARENICLINE plasma
Homo sapiens
9.22 ng/mL
1 mg 2 times / day multiple, oral
VARENICLINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
106 ng × h/mL
1 mg single, oral
VARENICLINE plasma
Homo sapiens
97.7 ng × h/mL
1 mg single, oral
VARENICLINE plasma
Homo sapiens
186 ng × h/mL
1 mg 2 times / day steady-state, oral
VARENICLINE plasma
Homo sapiens
194 ng × h/mL
1 mg 2 times / day multiple, oral
VARENICLINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
10.9 h
1 mg single, oral
VARENICLINE plasma
Homo sapiens
11.1 h
1 mg single, oral
VARENICLINE plasma
Homo sapiens
24 h
1 mg 2 times / day steady-state, oral
VARENICLINE plasma
Homo sapiens
33 h
1 mg 2 times / day multiple, oral
VARENICLINE plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
Begin CHANTIX (Varenicline) dosing one week before the date set by the patient to stop smoking. Alternatively, the patient can begin CHANTIX dosing and then quit smoking between days 8 and 35 of treatment. (2.1) • Starting week: 0.5 mg once daily on days 1-3 and 0.5 mg twice daily on days 4-7. (2.1) • Continuing Weeks: 1 mg twice daily for a total of 12 weeks. (2.1) • An additional 12 weeks of treatment is recommended for successful quitters to increase likelihood of long-term abstinence. (2.1) • Consider a gradual approach to quitting smoking with CHANTIX for patients who are sure that they are not able or willing to quit abruptly. Patients should begin CHANTIX dosing and reduce smoking by 50% from baseline within the first four weeks, by an additional 50% in the next four weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks. Continue treatment for an additional 12 weeks, for a total of 24 weeks. (2.1) CHANTIX should be taken orally after eating and with a full glass of water.
Route of Administration: Oral
In Vitro Use Guide
Varenicline potently desensitized the α4β2 nAChR with IC50 value of 420 nM
Substance Class Chemical
Record UNII
82269ASB48
Record Status Validated (UNII)
Record Version