Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C10H14N2 |
Molecular Weight | 162.2316 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCC[C@H]1C2=CN=CC=C2
InChI
InChIKey=SNICXCGAKADSCV-JTQLQIEISA-N
InChI=1S/C10H14N2/c1-12-7-3-5-10(12)9-4-2-6-11-8-9/h2,4,6,8,10H,3,5,7H2,1H3/t10-/m0/s1
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 |
DescriptionSources: www.inchem.org/documents/pims/chemical/nicotine.htmCurator'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/
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1907589 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15528443 |
7.9 null [pKi] | ||
Target ID: CHEMBL1907594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22148173 |
260.0 nM [Ki] | ||
Target ID: CHEMBL2492 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15528443 |
3.0 µM [Ki] | ||
Target ID: CHEMBL2109238 |
|||
Target ID: Nicotinic acetylcholine receptors |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | NICORETTE Approved UseReduces withdrawal symptoms, including nicotine craving associated with quitting smoking Launch Date1984 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
6 mg single, oral Highest studied dose |
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 |
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) Sources: Nausea (1 patient) |
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) Sources: Nausea (grade 2-3, 2 patients) |
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
AE | Significance | Dose | Population |
---|---|---|---|
Bradycardia | 1 patient Disc. AE |
6 mg single, oral Highest studied dose |
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 |
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: - |
no | |||
Page: - |
yes | |||
Page: - |
yes | |||
Page: - |
yes | |||
Page: - |
yes | |||
Page: - |
yes | |||
Page: - |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 245.0 |
minor | |||
Page: 245.0 |
minor | |||
Sources: https://molpharm.aspetjournals.org/content/72/3/761 Page: - |
no | |||
Page: - |
yes | |||
Page: 245.0 |
yes | |||
Page: - |
yes | |||
Page: 60.0 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/17909004/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20876810/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20876810/ Page: - |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: - |
PubMed
Title | Date | PubMed |
---|---|---|
Chronic nicotine pretreatment protects the blood-brain barrier against nicotine-induced seizures in the rat. | 1999 Sep |
|
Deficient cotinine formation from nicotine is attributed to the whole deletion of the CYP2A6 gene in humans. | 2000 Jan |
|
CYP2A6 genetic polymorphisms and liver microsomal coumarin and nicotine oxidation activities in Japanese and Caucasians. | 2000 Jan |
|
Dermal exposure to pesticides modifies antioxidant enzymes in tissues of rats. | 2000 Jul |
|
Antioxidant effect of onion oil (Allium cepa. Linn) on the damages induced by nicotine in rats as compared to alpha-tocopherol. | 2000 Jul 27 |
|
Nicotine switches the form of H(2)O(2)-induced cell death from apoptosis to necrosis in U937 cells. | 2000 Jun 1 |
|
An animal model of adolescent nicotine exposure: effects on gene expression and macromolecular constituents in rat brain regions. | 2000 Jun 9 |
|
Prenatal nicotine exposure is associated with an increase in [125I]epibatidine binding in discrete cortical regions in rats. | 2000 Oct |
|
Effects of nicotine on the intervertebral disc: an experimental study in rabbits. | 2001 |
|
Chronic nicotine exposure reduces N-methyl-D-aspartate receptor-mediated damage in the hippocampus without altering calcium accumulation or extrusion: evidence of calbindin-D28K overexpression. | 2001 |
|
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 |
|
Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro. | 2001 Jun |
|
Reversal of diminished inhibitory sensory gating in cocaine addicts by a nicotinic cholinergic mechanism. | 2001 Jun |
|
A novel single nucleotide polymorphism altering stability and activity of CYP2a6. | 2001 Mar 2 |
|
Activation of 5-HT(2C) receptors reduces the locomotor and rewarding effects of nicotine. | 2001 Sep |
|
Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco. | 2001 Sep 21 |
|
Fetal and adolescent nicotine administration: effects on CNS serotonergic systems. | 2001 Sep 28 |
|
[Acute confusional syndrome due to acute nicotine withdrawal]. | 2002 |
|
Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. | 2002 Feb |
|
An in vivo pilot study characterizing the new CYP2A6*7, *8, and *10 alleles. | 2002 Jan 11 |
|
Involvement of human heat shock protein 90 alpha in nicotine-induced apoptosis. | 2002 Jul 1 |
|
beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure. | 2002 Oct 1 |
|
Lasting effects of adolescent nicotine exposure on the electroencephalogram, event related potentials, and locomotor activity in the rat. | 2002 Sep 20 |
|
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22148173
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
Edited
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by
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Fri Dec 15 15:07:38 GMT 2023
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Record UNII |
6M3C89ZY6R
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C221
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LIVERTOX |
NBK548698
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WHO-ATC |
N07BA01
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NDF-RT |
N0000175706
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WHO-VATC |
QP53AX13
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WHO-VATC |
QN07BA01
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EPA PESTICIDE CODE |
56702
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NDF-RT |
N0000006496
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NCI_THESAURUS |
C73579
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NDF-RT |
N0000006496
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D009538
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7407
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100000079991
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2585
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C691
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Nicotine replacement therapy
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17688
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1107
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NICOTINE
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CHEMBL3
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DB00184
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SUB14645MIG
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Nicotine
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54-11-5
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nicotine
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SUB30160
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1920
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m7879
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5065
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200-193-3
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Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE | |||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
EP
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TARGET -> AGONIST |
NICOTINE IS AN ANTIHERBIVORY ALKALOID AND POTENT PARASYMPATHOMIMETIC STIMULANT AND FOUND IN PLANTS, MOSTLY THOSE IN THE NIGHTSHADE FAMILY. NICOTINE ACTS AS A RECEPTOR AGONIST AT MOST NICOTINIC ACETYLCHOLINE RECEPTORS (NACHRS), EXCEPT AT TWO NICOTINIC RECEPTOR SUBUNITS (NACHR.ALPHA.9 AND NACHR.ALPHA.10) WHERE IT ACTS AS A RECEPTOR ANTAGONIST.
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
USP
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SALT/SOLVATE -> PARENT | |||
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DERIVATIVE -> PARENT |
Carcinogenic substance present in cigarette smoke
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT | |||
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> INHIBITOR |
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TARGET -> INHIBITOR |
BINDING
IC50
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METABOLIC ENZYME -> SUBSTRATE | |||
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SUB_CONCEPT->SUBSTANCE | |||
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SALT/SOLVATE -> PARENT | |||
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PARENT -> CONSTITUENT ALWAYS PRESENT |
Nicotine (mg/cigarette)
Domestic = 12.6 SD(1.6)
Imported = 11.1 SD(2.2)
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT | |||
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LABELED -> NON-LABELED | |||
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INHIBITOR -> TARGET |
BINDS TO NICOTINE PREVENTS ACTION
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SUB_CONCEPT->SUBSTANCE | |||
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SALT/SOLVATE -> PARENT |
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Related Record | Type | Details | ||
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METABOLITE LESS ACTIVE -> PARENT |
75% is converted into cotintine which is further metabolized.
MAJOR
PLASMA; URINE
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METABOLITE -> PARENT |
circulating nicotine is metabolized to cotinine by cytochrome P450 and aldehyde oxidase
MAJOR
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METABOLITE -> PARENT |
in animals both N-oxide isomers form, in humans only the transisomers form.
MAJOR
URINE
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METABOLITE -> PARENT |
The extent of nicotine N-glucuronidation by African Americans is significantly lower than by Whites.
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METABOLITE -> PARENT |
PLASMA; URINE
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METABOLITE -> PARENT |
The extent of Cotinine N-glucuronidation by African Americans is significantly lower than by Whites.
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METABOLITE INACTIVE -> PARENT |
Related Record | Type | Details | ||
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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