VARENICLINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H13N3
Molecular Weight	211.2624
Optical Activity	NONE
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1[C@H]2CNC[C@@H]1C3=C2C=C4N=CC=NC4=C3

InChI

InChIKey=JQSHBVHOMNKWFT-DTORHVGOSA-N

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+

HIDE SMILES / InChI

Molecular Formula	C13H13N3
Molecular Weight	211.2624
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugbank.ca/drugs/DB01273
Curator's Comment: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021928s039s041lbl.pdf

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 Target	Pharmacology	Condition	Potency
Neuronal acetylcholine receptor; alpha4/beta2 77 Target ID: CHEMBL1907589 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021928s039s041lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/22591063 \| https://www.ncbi.nlm.nih.gov/pubmed/16766716	Partial Agonist 297		0.4 nM [Ki]
Neuronal acetylcholine receptor protein alpha-7 subunit 78 Target ID: CHEMBL2492 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24406270	Agonist 2752		130.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Nicotine dependence 33 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021928s039s041lbl.pdf	Curative		Approved 8583	CHANTIX Approved Use CHANTIX is a nicotinic receptor partial agonist indicated for use as an aid to smoking cessation treatment. Launch Date 2006

C_max

Value	Dose	Analyte	Population
5.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920893/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	VARENICLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
9.22 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/21053991/	1 mg 2 times / day multiple, oral dose: 1 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VARENICLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.38 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21053991/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	VARENICLINE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
97.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920893/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	VARENICLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
186 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19916991/	1 mg 2 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VARENICLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
194 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/21053991/	1 mg 2 times / day multiple, oral dose: 1 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VARENICLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
106 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21053991/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	VARENICLINE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
11.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920893/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	VARENICLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
24 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19916991/	1 mg 2 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VARENICLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33 h REVIEW https://pubmed.ncbi.nlm.nih.gov/21053991/	1 mg 2 times / day multiple, oral dose: 1 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VARENICLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21053991/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	VARENICLINE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296 P-gp 1741 OCT2 779	OCT2 434 P-gp 2052 CYP 303 UGT enzymes 27	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no [IC50 >30 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 36.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 36.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 36.0	no	no (co-administration study) Comment: digoxin remained unchanged in the presence of varenicline Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 36.0
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_PharmR.pdf Page: 72.0	weak

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP 303	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 35.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 36.0	no	no (co-administration study) Comment: digoxin remained unchanged in the presence of varenicline Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 36.0
UGT enzymes 27	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_BioPharmR.pdf Page: 37, 272, 276	yes
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_PharmR.pdf Page: 46, 72	yes	yes (co-administration study) Comment: cimetidine increased the systemic exposure of varenicline by 29% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_PharmR.pdf Page: 46, 72

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_PharmR.pdf Page: 39.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:84500	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:84500
eMolecules	36500513	https://www.emolecules.com/cgi-bin/more?vid=36500513
MolPort	MolPort-006-167-759	https://www.molport.com/shop/molecule-link/MolPort-006-167-759
ZINC	ZINC000001481833	http://zinc15.docking.org/substances/ZINC000001481833

PubMed

Title	Date	PubMed
Cytisine for smoking cessation: a research agenda.	2008-01-01	17825502
Neuronal nicotinic receptors: a perspective on two decades of drug discovery research.	2007-10-15	17662959
Smoking cessation interventions in clinical practice.	2007-10	17681834
A call to action: new treatment options provide even more reasons to intervene in tobacco dependence.	2007-09	17646852
Emerging pharmacotherapies for smoking cessation.	2007-08-15	17687057
Optimizing on smoke free legislation making the most of the opportunity.	2007-08	17851296
Varenicline: progress in smoking cessation treatment.	2007-08	17685891
Exacerbation of schizophrenia by varenicline.	2007-08	17671295
Varenicline-induced manic episode in a patient with bipolar disorder.	2007-08	17671294
[New smoking cessation preparations unsuitable in mental disorders].	2007-07-28	17655031
Kicking butts: smoking cessation update.	2007-07-11	17619503
The pharmacist's role in tobacco cessation: overview and introduction to the series.	2007-07-01	17592012
Varenicline: the newest agent for smoking cessation.	2007-07-01	17592002
Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation.	2007-07	17573127
Smoking cessation: lessons learned from clinical trial evidence.	2007-07	17556878
New non-nicotine drug to help smoking cessation efforts.	2007-06-30	17598689
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.	2007-06	17692720
A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers.	2007-06	17692719
How well does the new drug varenicline work for people who want to stop smoking?	2007-06	17657893
Smoking cessation update.	2007-06	17649863
Why choose varenicline (chantix) for smoking cessation treatment?	2007-06	17613164
Alcohol history and smoking cessation in nicotine replacement therapy, bupropion sustained release and varenicline trials: a review.	2007-05-29	17526629
Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation.	2007-04-18	17438382
An employer-based cost-benefit analysis of a novel pharmacotherapy agent for smoking cessation.	2007-04	17426529
A double-blind study evaluating the long-term safety of varenicline for smoking cessation.	2007-04	17407636
Comment: Oral varenicline for smoking cessation.	2007-04	17374627
The most addictive drug, the most deadly substance: smoking cessation tactics for the busy clinician.	2007-03	17481990
[Varenicline--a new drug for smoking cessation].	2007-03	17405480
[The path from cigarettes--with support it works better].	2007-03	17405479
[Giving up smoking is crucial for COPD patients].	2007-02-22	17615702
Smoking cessation efficacy and safety of varenicline, an alpha4beta2 nicotinic receptor partial agonist.	2007-02-13	17293731
[Drug of the month. Varenicline (Champix)].	2007-02	17461303
Varenicline: new treatment with efficacy in smoking cessation.	2007-02	17353944
Varenicline for smoking cessation.	2007-02	17286546
Drug approvals.	2007-02	17264794
Smoking cessation in patients with respiratory diseases: a high priority, integral component of therapy.	2007-02	17264326
Impact of pharmacometric reviews on new drug approval and labeling decisions--a survey of 31 new drug applications submitted between 2005 and 2006.	2007-02	17259946
[Champix has become a registered drug].	2007-01-28	17344137
Nicotine receptor partial agonists for smoking cessation.	2007-01-24	17253581
Antidepressants for smoking cessation.	2007-01-24	17253443
[The best of epidemiology and cardiovascular prevention in 2006].	2007-01	17405566
Smoking: tackling the silent epidemic.	2007	17824207
Rimonabant for treating tobacco dependence.	2007	17703638
[Varenicline (Champix)].	2007	17508668
[Tobacco use prevention and cessation in the dental practice].	2007	17425242
Maximizing smoking cessation in clinical practice: pharmacologic and behavioral interventions.	2007	17396064
Smoking cessation pharmacotherapy--nicotine and non-nicotine preparations.	2007	17396063
A clinical imperative: assisting patients who smoke to reduce their risk of cardiovascular disease.	2007	17396062
Varenicline (CHANTIX): a stop-smoking pill.	2006	17390707
Treating smoking dependence in depressed alcoholics.	2006	17373412

Patents

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 Created by `admin` on `Mon Mar 31 18:03:44 GMT 2025` Edited by `admin` on `Mon Mar 31 18:03:44 GMT 2025`
Record UNII	W6HS99O8ZO
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CP-526,555

Preferred Name

English

VARENICLINE

Official Name

English

VARENICLINE [MI]

Common Name

English

VARENICLINE [EMA EPAR]

Common Name

English

VARENICLINE [HSDB]

Common Name

English

VARENICLINE [VANDF]

Common Name

English

VARENICLINE [MART.]

Common Name

English

CP-526555

Code

English

7,8,9,10-TETRAHYDRO-6H-6,10-METHANOAZEPINO(4,5-G)QUINOXALINE

Systematic Name

English

varenicline [INN]

Common Name

English

Varenicline [WHO-DD]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175702