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

Details

Stereochemistry ABSOLUTE
Molecular Formula C10H14N2.2C4H6O6.2H2O
Molecular Weight 498.4358
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NICOTINE BITARTRATE

SMILES

O.O.O[C@H]([C@@H](O)C(O)=O)C(O)=O.O[C@H]([C@@H](O)C(O)=O)C(O)=O.CN1CCC[C@H]1C2=CN=CC=C2

InChI

InChIKey=LDMPZNTVIGIREC-ZGPNLCEMSA-N
InChI=1S/C10H14N2.2C4H6O6.2H2O/c1-12-7-3-5-10(12)9-4-2-6-11-8-9;2*5-1(3(7)8)2(6)4(9)10;;/h2,4,6,8,10H,3,5,7H2,1H3;2*1-2,5-6H,(H,7,8)(H,9,10);2*1H2/t10-;2*1-,2-;;/m011../s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C10H14N2
Molecular Weight 162.2316
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Sources: www.inchem.org/documents/pims/chemical/nicotine.htm
Curator's Comment: description was created based on several sources, including https://cancercontrol.cancer.gov/brp/tcrb/monographs/1/index.html https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928221/

Nicotine is a natural alkaloid obtained from the dried leaves and stems of the nightshade family of pants, such as Nicotiana tabacum and Nicotiana rustica, where it occurs in concentrations of 0.5-8%. Cigarette tobacco varies in its nicotine content, but common blends contain 15-25 mg per cigarette, with a current trend towards lower levels. Nicotine is highly addictive substance, it exhibits a stimulant effect when adsorbed at 2 mg. Administration of higher doses could be harmful. Action of nicotine is mediated by nicotinic cholinergic receptors. Nicotine binds to the interface between two subunits of the receptors, opens the channel and allows the entry of sodium or calcium. The principal mediator of nicotine dependence is α4β2 nicotine receptor.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
NICORETTE

Approved Use

Reduces withdrawal symptoms, including nicotine craving associated with quitting smoking

Launch Date

1984
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
12 ng/mL
1 mg single, nasal
dose: 1 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NICOTINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6 ng × h/mL
1 mg single, nasal
dose: 1 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NICOTINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3 min
1 mg single, nasal
dose: 1 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NICOTINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
95%
1 mg single, nasal
dose: 1 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NICOTINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
6 mg single, oral
Highest studied dose
Dose: 6 mg
Route: oral
Route: single
Dose: 6 mg
Sources:
healthy, 19 - 49 years
n = 44
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 49 years
Sex: M+F
Population Size: 44
Sources:
Disc. AE: Bradycardia...
AEs leading to
discontinuation/dose reduction:
Bradycardia (1 patient)
Sources:
4 mg single, oral
Studied dose
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources:
healthy, 19 - 49 years
n = 44
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 49 years
Sex: M+F
Population Size: 44
Sources:
Disc. AE: Allergic dermatitis...
AEs leading to
discontinuation/dose reduction:
Allergic dermatitis (1 patient)
Sources:
6 mg 1 times / hour steady, oral
Highest studied dose
Dose: 6 mg, 1 times / hour
Route: oral
Route: steady
Dose: 6 mg, 1 times / hour
Sources:
healthy, 19 - 50 years
n = 50
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 50 years
Sex: M+F
Population Size: 50
Sources:
Disc. AE: Hypersensitivity, Nausea...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity (1 patient)
Nausea (1 patient)
Sources:
8 mg 1 times / hour steady, oral
Highest studied dose
Dose: 8 mg, 1 times / hour
Route: oral
Route: steady
Dose: 8 mg, 1 times / hour
Sources:
healthy, 19 - 50 years
n = 50
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 50 years
Sex: M+F
Population Size: 50
Sources:
Disc. AE: Depression, Nausea...
AEs leading to
discontinuation/dose reduction:
Depression (1 patient)
Nausea (grade 2-3, 2 patients)
Sources:
111 mg single, transdermal
Overdose
Dose: 111 mg
Route: transdermal
Route: single
Dose: 111 mg
Sources:
healthy, 41 years
n = 1
Health Status: healthy
Condition: adult smoker
Age Group: 41 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 1 patient)
Sources:
84 mg 1 times / day steady, transdermal
Highest studied dose
Dose: 84 mg, 1 times / day
Route: transdermal
Route: steady
Dose: 84 mg, 1 times / day
Sources:
healthy, adult
n = 36
Health Status: healthy
Condition: adult smokers
Age Group: adult
Sex: unknown
Population Size: 36
Sources:
Other AEs: Nausea...
AEs

AEs

AESignificanceDosePopulation
Bradycardia 1 patient
Disc. AE
6 mg single, oral
Highest studied dose
Dose: 6 mg
Route: oral
Route: single
Dose: 6 mg
Sources:
healthy, 19 - 49 years
n = 44
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 49 years
Sex: M+F
Population Size: 44
Sources:
Allergic dermatitis 1 patient
Disc. AE
4 mg single, oral
Studied dose
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources:
healthy, 19 - 49 years
n = 44
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 49 years
Sex: M+F
Population Size: 44
Sources:
Hypersensitivity 1 patient
Disc. AE
6 mg 1 times / hour steady, oral
Highest studied dose
Dose: 6 mg, 1 times / hour
Route: oral
Route: steady
Dose: 6 mg, 1 times / hour
Sources:
healthy, 19 - 50 years
n = 50
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 50 years
Sex: M+F
Population Size: 50
Sources:
Nausea 1 patient
Disc. AE
6 mg 1 times / hour steady, oral
Highest studied dose
Dose: 6 mg, 1 times / hour
Route: oral
Route: steady
Dose: 6 mg, 1 times / hour
Sources:
healthy, 19 - 50 years
n = 50
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 50 years
Sex: M+F
Population Size: 50
Sources:
Depression 1 patient
Disc. AE
8 mg 1 times / hour steady, oral
Highest studied dose
Dose: 8 mg, 1 times / hour
Route: oral
Route: steady
Dose: 8 mg, 1 times / hour
Sources:
healthy, 19 - 50 years
n = 50
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 50 years
Sex: M+F
Population Size: 50
Sources:
Nausea grade 2-3, 2 patients
Disc. AE
8 mg 1 times / hour steady, oral
Highest studied dose
Dose: 8 mg, 1 times / hour
Route: oral
Route: steady
Dose: 8 mg, 1 times / hour
Sources:
healthy, 19 - 50 years
n = 50
Health Status: healthy
Condition: adult smokers
Age Group: 19 - 50 years
Sex: M+F
Population Size: 50
Sources:
Death grade 5, 1 patient
Disc. AE
111 mg single, transdermal
Overdose
Dose: 111 mg
Route: transdermal
Route: single
Dose: 111 mg
Sources:
healthy, 41 years
n = 1
Health Status: healthy
Condition: adult smoker
Age Group: 41 years
Sex: M
Population Size: 1
Sources:
Nausea
84 mg 1 times / day steady, transdermal
Highest studied dose
Dose: 84 mg, 1 times / day
Route: transdermal
Route: steady
Dose: 84 mg, 1 times / day
Sources:
healthy, adult
n = 36
Health Status: healthy
Condition: adult smokers
Age Group: adult
Sex: unknown
Population Size: 36
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Treatment outcome in tobacco dependence after nicotine replacement therapy and group therapy].
1999
Inducible, heterologous expression of human alpha7-nicotinic acetylcholine receptors in a native nicotinic receptor-null human clonal line.
1999 Apr 17
Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant.
1999 Feb 5
Predictors and timing of adverse experiences during trandsdermal nicotine therapy.
1999 Jun
Chronic nicotine pretreatment protects the blood-brain barrier against nicotine-induced seizures in the rat.
1999 Sep
Mimicking gene defects to treat drug dependence.
2000
Chick optic lobe contains a developmentally regulated alpha2alpha5beta2 nicotinic receptor subtype.
2000 Aug
Nicotinic receptor function: new perspectives from knockout mice.
2000 Jun
Nicotine-induced nystagmus: three-dimensional analysis and dependence on head position.
2000 Nov 28
Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior.
2000 Oct
Duplications and defects in the CYP2A6 gene: identification, genotyping, and in vivo effects on smoking.
2000 Oct
Effects of nicotine on the intervertebral disc: an experimental study in rabbits.
2001
Formation of the quaternary ammonium-linked glucuronide of nicotine in human liver microsomes: identification and stereoselectivity in the kinetics.
2001 Dec
Contributory role for nornicotine in nicotine neuropharmacology: nornicotine-evoked [3H]dopamine overflow from rat nucleus accumbens slices.
2001 Dec 15
Nicotine inhibits UV-induced activation of the apoptotic pathway.
2001 Dec 15
Tolerance to nicotine's effects in the elevated plus-maze and increased anxiety during withdrawal.
2001 Feb
Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers.
2001 Jul
Nicotine produces selective degeneration in the medial habenula and fasciculus retroflexus.
2001 Jul 6
Nicotinic regulation of c-fos and osteopontin expression in human-derived osteoblast-like cells and human trabecular bone organ culture.
2001 Jun
Reversal of diminished inhibitory sensory gating in cocaine addicts by a nicotinic cholinergic mechanism.
2001 Jun
An immunotherapeutic program for the treatment of nicotine addiction: hapten design and synthesis.
2001 Jun 15
Smoking and balance: correlation of nicotine-induced nystagmus and postural body sway.
2001 May 8
Nicotine induced seizures blocked by mecamylamine and its stereoisomers.
2001 Oct 19
Acute myocardial infarction soon after nicotine replacement therapy.
2001 Sep
[Acute confusional syndrome due to acute nicotine withdrawal].
2002
Molecular orbital calculations and nicotine metabolism: a rationale for experimentally observed metabolite ratios.
2002
Microsomal N-glucuronidation of nicotine and cotinine: human hepatic interindividual, human intertissue, and interspecies hepatic variation.
2002 Dec
Increased sensitivity to nicotine-induced seizures in mice heterozygous for the L250T mutation in the alpha7 nicotinic acetylcholine receptor.
2002 Feb 11
Enhancement of cocaine-seeking behavior by repeated nicotine exposure in rats.
2002 Jul
The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats differ in sensitivity to nicotine.
2002 Jun
Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism.
2002 Nov
Nicotine's oxidative and antioxidant properties in CNS.
2002 Nov 1
CYP2A6 genetic variation and potential consequences.
2002 Nov 18
Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence.
2002 Oct
beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure.
2002 Oct 1
[Review of current etiopathogenic data of Buerger disease].
2002 Sep
Lasting effects of adolescent nicotine exposure on the electroencephalogram, event related potentials, and locomotor activity in the rat.
2002 Sep 20
Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats.
2003 Jan
Oral caffeine maintenance potentiates the reinforcing and stimulant subjective effects of intravenous nicotine in cigarette smokers.
2003 Jan
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis.
2003 Jan 17
Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
2004 Jun
Nicotine addiction.
2010 Jun 17
How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century.
2014 Jan
Patents

Sample Use Guides

Reduces withdrawal symptoms, including nicotine craving associated with quitting smoking, nicotine is available as a chewing gum, and is administered according to a schedule at doses 2-4 mg once every 2-4 hours. Nicotine is also available as a transdermal patch.
Route of Administration: Other
Functional activity of nicotine against hα4β2 nicotinic receptors was evaluated using the 86Rb+ ion flux assay in SH-EP1 cells, expressing hα4β2. The 86Rb+ efflux was measured using the “flip-plate” technique. Nicotine activated 86Rb+ efflux with EC50 of 290 nM.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:28:07 GMT 2023
Edited
by admin
on Fri Dec 15 16:28:07 GMT 2023
Record UNII
R7M676M8YV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NICOTINE BITARTRATE
USAN   WHO-DD  
USAN  
Official Name English
NICOTINE (AS BITARTRATE)
Common Name English
Nicotine bitartrate dihydrate [WHO-DD]
Common Name English
NICOTINE DITARTRATE DIHYDRATE
EP  
Systematic Name English
NICOTINE BITARTRATE [USAN]
Common Name English
3-((2S)-1-METHYL-2-PYRROLIDINYL)PYRIDINE, (2R,3R)-2,3-DIHYDROXYBUTANEDIOATE (1:2), DIHYDRATE
Common Name English
NICOTINE BITARTRATE DIHYDRATE
USP-RS  
Systematic Name English
NICOTINE DITARTRATE DIHYDRATE [EP MONOGRAPH]
Common Name English
Nicotine bitartrate [WHO-DD]
Common Name English
NICOTINE DITARTRATE DIHYDRATE [EP IMPURITY]
Common Name English
NICOTINE ACID TARTRATE DIHYDRATE
Common Name English
PYRIDINE, 3-((2S)-1-METHYL-2-PYRROLIDINYL)-, (2R,3R)-2,3-DIHYDROXYBUTANEDIOATE, HYDRATE (1:2:2)
Systematic Name English
Code System Code Type Description
NCI_THESAURUS
C170219
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
EVMPD
SUB39891
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
SMS_ID
100000129686
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
RXCUI
1306107
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY RxNorm
FDA UNII
R7M676M8YV
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
ChEMBL
CHEMBL3
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
RS_ITEM_NUM
1463304
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
CAS
6019-06-3
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
USAN
LL-108
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
EVMPD
SUB22391
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
DRUG BANK
DBSALT002418
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
PUBCHEM
2735102
Created by admin on Fri Dec 15 16:28:07 GMT 2023 , Edited by admin on Fri Dec 15 16:28:07 GMT 2023
PRIMARY
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