Nicotine

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Identification

Summary

Nicotine is a stimulatory alkaloid found in tobacco products that is often used for the relief of nicotine withdrawal symptoms and as an aid to smoking cessation.

Brand Names

Habitrol, Nicoderm C-Q, Nicorelief, Nicorette, Nicotrol

Generic Name

Nicotine

DrugBank Accession Number

DB00184

Background

Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 162.2316
Monoisotopic: 162.115698458
Chemical Formula: C₁₀H₁₄N₂

Synonyms

(−)-nicotine
(S)-(−)-nicotine
(S)-3-(1-methylpyrrolidin-2-yl)pyridine
(S)-3-(N-methylpyrrolidin-2-yl)pyridine
(S)-Nicotine
3-(2-(N-methylpyrrolidinyl))pyridine
3-(N-methylpyrollidino)pyridine
L(−)-nicotine
Nicotina
Nicotine
Nicotine betadex
Nicotine polacrilex
Nikotin
Nikotyna

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Pharmacology

Indication

For the relief of nicotine withdrawal symptoms and as an aid to smoking cessation.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Management of	Withdrawal nicotine		••••••••••••	•••••

Associated Therapies

Smoking cessation therapy

Contraindications & Blackbox Warnings

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Pharmacodynamics

Nicotine, the primary alkaloid in tobacco products binds stereo-selectively to nicotinic-cholinergic receptors on autonomic ganglia, the adrenal medulla, neuromuscular junctions and in the brain. Nicotine exerts two effects, a stimulant effect exerted at the locus ceruleus and a reward effect in the limbic system. Itranvenous administration of nicotine causes release of acetylcholine, norepinephrine, dopamine, serotonine, vasopressin, beta-endorphin and ACTH. Nicotine is a highly addictive substance. Nicotine also induces peripheral vasoconstriction, tachycardia and elevated blood pressure. Nicotine inhalers and patches are used to treat smoking withdrawl syndrome. Nicotine is classified as a stimulant of autonomic ganglia.

Mechanism of action

Nicotine is a stimulant drug that acts as an agonist at nicotinic acetylcholine receptors. These are ionotropic receptors composed up of five homomeric or heteromeric subunits. In the brain, nicotine binds to nicotinic acetylcholine receptors on dopaminergic neurons in the cortico-limbic pathways. This causes the channel to open and allow conductance of multiple cations including sodium, calcium, and potassium. This leads to depolarization, which activates voltage-gated calcium channels and allows more calcium to enter the axon terminal. Calcium stimulates vesicle trafficking towards the plasma membrane and the release of dopamine into the synapse. Dopamine binding to its receptors is responsible the euphoric and addictive properties of nicotine. Nicotine also binds to nicotinic acetylcholine receptors on the chromaffin cells in the adrenal medulla. Binding opens the ion channel allowing influx of sodium, causing depolarization of the cell, which activates voltage-gated calcium channels. Calcium triggers the release of epinephrine from intracellular vesicles into the bloodstream, which causes vasoconstriction, increased blood pressure, increased heart rate, and increased blood sugar.

Target	Actions	Organism
ANeuronal acetylcholine receptor subunit alpha-4	agonist	Humans
ANeuronal acetylcholine receptor subunit alpha-7	agonist	Humans
ANeuronal acetylcholine receptor subunit beta-2	agonist	Humans
UNeuronal acetylcholine receptor subunit alpha-2	agonist	Humans
UNeuronal acetylcholine receptor subunit alpha-3	agonist	Humans
UNeuronal acetylcholine receptor subunit alpha-5	agonist	Humans
UNeuronal acetylcholine receptor subunit alpha-6	agonist	Humans
UNeuronal acetylcholine receptor subunit alpha-9	agonist	Humans
UNeuronal acetylcholine receptor subunit alpha-10	agonist	Humans
UNeuronal acetylcholine receptor subunit beta-3	agonist	Humans
UNeuronal acetylcholine receptor subunit beta-4	agonist	Humans
UAromatase	inhibitor	Humans
UCholine O-acetyltransferase	inhibitor	Humans

Absorption

Absorption of nicotine through the buccal mucosa is relatively slow and the high and rapid rise followed by the decline in nicotine arterial plasma concentrations seen with cigarette smoking are not achieved with the inhaler. About 10% of absorbed nicotine is excreted unchanged in urine.

Volume of distribution

2 to 3 L/kg

Protein binding

Less than 5%

Metabolism

Primarily hepatic, cotinine is the primary metabolite.

Hover over products below to view reaction partners

Nicotine

Route of elimination

About 10% of the nicotine absorbed is excreted unchanged in the urine.

Half-life

Cotinine has a half life of 15-20 hours, while nicotine has a half life of 1-3 hours

Clearance

1.2 L/min [healthy adult smoker]

Adverse Effects

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Toxicity

Symptoms of overdose include nausea, abdominal pain, vomiting, diarrhea, diaphoresis, flushing, dizziness, disturbed hearing and vision, confusion, weakness, palpitations, altered respiration and hypotension. LD₅₀= 24 mg/kg (orally in mice).

Pathways

Pathway	Category
Nicotine Action Pathway	Drug action
Nicotine Metabolism Pathway	Drug metabolism

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abametapir	The serum concentration of Nicotine can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Nicotine can be increased when combined with Abatacept.
Acebutolol	The risk or severity of adverse effects can be increased when Acebutolol is combined with Nicotine.
Acetaminophen	Nicotine may increase the hepatotoxic activities of Acetaminophen.
Acetazolamide	The risk or severity of adverse effects can be increased when Acetazolamide is combined with Nicotine.

Food Interactions

Take separate from meals. For nicotine gum, lozenges, and oral sprays, avoid eating and drinking for 15 minutes before and during its use.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Nicotine bitartrate	7892ZN5G41	65-31-6	RFEJUZJILGIRHQ-OMDKHLBYSA-N
Nicotine bitartrate dihydrate	R7M676M8YV	6019-06-3	LDMPZNTVIGIREC-ZGPNLCEMSA-N

Product Images

International/Other Brands

Habitrol / Nicoderm

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Nicorette Invisipatch	Patch	25 mg / 16 hour	Transdermal	Mcneil Consumer Healthcare Division Of Johnson & Johnson Inc	Not applicable	Not applicable
Nicotine Polacrilex	Powder	180 g/1kg	Oral	Nicobrand Ltd.	1994-02-01	2010-12-08
Nicotine Polacrilex	Powder	200 g/1kg	Oral	Nicobrand Ltd.	1994-02-01	2010-12-08
Nicotine Polacrilex	Powder	150 g/1kg	Oral	Nicobrand Ltd.	1994-02-01	2010-12-08
Nicotine Tartrate	Powder	1 kg/1kg	Oral	Nicobrand Ltd.	1997-07-11	Not applicable

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Amazon Basic Care Nicotine Polacrilex	Lozenge	2 mg/1	Oral	Amazon.com Services LLC	2024-05-15	Not applicable
Amazon Basic Care Nicotine Polacrilex	Lozenge	4 mg/1	Oral	Amazon.com Services LLC	2024-05-15	Not applicable
Amazon Basic Care Nicotine Polacrilex	Lozenge	2 mg/1	Oral	Amazon.com Services LLC	2024-05-15	Not applicable
Amazon Basic Care Nicotine Polacrilex	Lozenge	4 mg/1	Oral	Amazon.com Services LLC	2024-05-15	Not applicable
American Fare Nicotine Transdermal System	Patch, extended release	14 mg/1	Transdermal	GlaxoSmithKline Consumer Healthcare Holdings (US) LLC	2012-01-02	2014-12-29

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Basic Care Nicotine	Nicotine (2 mg/1) + Nicotine (2 mg/1)	Kit	Oral	L. Perrigo Company	2019-01-16	Not applicable
Basic Care Nicotine	Nicotine (2 mg/1) + Nicotine (2 mg/1)	Kit	Oral	L. Perrigo Company	2019-01-16	Not applicable
Nicorette and Aquafresh Fruit Chill and Extreme Clean Whitening	Nicotine (4 mg/1) + Sodium fluoride (1.13 mg/1g)	Gum, chewing; Kit; Paste	Dental; Oral	GlaxoSmithKline Consumer Healthcare Holdings (US) LLC	2015-12-07	2018-06-30
Nicotine	Nicotine (2 mg/1) + Nicotine (2 mg/1)	Kit; Lozenge	Oral	CVS PHARMACY	2018-04-09	Not applicable
Nicotine	Nicotine (4 mg/1) + Nicotine (4 mg/1)	Kit; Lozenge	Oral	CVS PHARMACY	2018-04-09	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Nicotine Polacrilex	Nicotine (180 g/1kg)	Powder	Oral	Nicobrand Ltd.	1994-02-01	2010-12-08
Nicotine Polacrilex	Nicotine (200 g/1kg)	Powder	Oral	Nicobrand Ltd.	1994-02-01	2010-12-08
Nicotine Polacrilex	Nicotine (150 g/1kg)	Powder	Oral	Nicobrand Ltd.	1994-02-01	2010-12-08
Nicotine Tartrate	Nicotine bitartrate (1 kg/1kg)	Powder	Oral	Nicobrand Ltd.	1997-07-11	Not applicable
Nicotine UN1654	Nicotine (1 L/1L)	Liquid	Oral	Nicobrand Ltd.	1997-07-11	Not applicable

Chemical Identifiers

UNII: 6M3C89ZY6R
CAS number: 54-11-5
InChI Key: SNICXCGAKADSCV-JTQLQIEISA-N
InChI: 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
IUPAC Name: 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
SMILES: CN1CCC[C@H]1C1=CN=CC=C1

References

Synthesis Reference

Charles G. Chavdarian, Edward B. Sanders, "Process for the preparation of optically active nicotine analogs." U.S. Patent US4321387, issued September, 1959.

US4321387

General References

Nolley EP, Kelley BM: Adolescent reward system perseveration due to nicotine: studies with methylphenidate. Neurotoxicol Teratol. 2007 Jan-Feb;29(1):47-56. Epub 2006 Oct 4. [Article]
de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ: Schizophrenia and tobacco smoking: a replication study in another US psychiatric hospital. Schizophr Res. 2002 Jul 1;56(1-2):55-65. [Article]
de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM: Schizophrenia and smoking: an epidemiological survey in a state hospital. Am J Psychiatry. 1995 Mar;152(3):453-5. [Article]
Aguilar MC, Gurpegui M, Diaz FJ, de Leon J: Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions. Br J Psychiatry. 2005 Mar;186:215-21. [Article]

External Links

Human Metabolome Database: HMDB0001934
KEGG Drug: D03365
KEGG Compound: C00745
PubChem Compound: 89594
PubChem Substance: 46506924
ChemSpider: 80863
BindingDB: 82070
RxNav: 31765
ChEBI: 17688
ChEMBL: CHEMBL3
ZINC: ZINC000000391812
Therapeutic Targets Database: DAP000175
PharmGKB: PA450626
PDBe Ligand: NCT
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
PDRhealth: PDRhealth Drug Page
Wikipedia: Nicotine

PDB Entries

1p2y / 1p7r / 1uw6 / 2yk1 / 4ejg / 4ejj / 5kxi / 5o87 / 6c71 / 6cnj …

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FDA label

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MSDS

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Clinical Trials

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Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data
Not Available	Active Not Recruiting	Health Services Research	Coronavirus Disease 2019 (COVID‑19) / Smoking, Cessation	1	somestatus	stop reason	just information to hide
Not Available	Active Not Recruiting	Health Services Research	Smoking, Cessation / Substance Related Disorders	1	somestatus	stop reason	just information to hide
Not Available	Active Not Recruiting	Other	Coronary Artery Disease (CAD) / Smoking, Cessation	1	somestatus	stop reason	just information to hide
Not Available	Active Not Recruiting	Other	Smoking, Cessation	1	somestatus	stop reason	just information to hide
Not Available	Active Not Recruiting	Prevention	Cigarette Smokers / Tobacco Use Disorders	1	somestatus	stop reason	just information to hide

Pharmacoeconomics

Manufacturers

Novartis consumer health inc
Sanofi aventis us llc
Aveva drug delivery systems inc
Mcneil consumer healthcare
Pharmacia and upjohn co
Pfizer inc
Glaxosmithkline
Ivax pharmaceuticals inc sub teva pharmaceuticals usa
Perrigo co
Perrigo r and d co
Watson laboratories inc
Glaxosmithkline consumer healthcare

Packagers

Aveva Drug Delivery Systems Inc.
Cardinal Health
CVS Pharmacy
Dispensing Solutions
Elan Pharmaceuticals Inc.
Gallipot
GlaxoSmithKline Inc.
LTS Lohmann Therapy Systems Corp.
Mckesson Corp.
McNeil Laboratories
Novartis AG
Perrigo Co.
Pfizer Inc.
Pharmacia Inc.
Physicians Total Care Inc.

Dosage Forms

Form	Route	Strength
Patch, extended release	Transdermal	14 mg/1
Kit	Oral
Patch, extended release	Transdermal	21 mg/1
Patch, extended release	Transdermal	7 mg/1
Lozenge	Oral	2 mg/1
Lozenge	Oral	4 mg/1
Patch, extended release	Transdermal	7 mg/24h
Patch	Transdermal	14 mg/1
Patch	Transdermal	21 mg/1
Patch	Transdermal	7 mg/1
Patch, extended release	Topical	21 mg/1
Patch, extended release	Topical	7 mg/1
Patch	Transdermal	114 mg / pad
Patch	Transdermal	36 mg / pad
Patch	Transdermal	78 mg / pad
Patch	Transdermal	31.5 mg
Patch	Transdermal	47.3 mg
Patch	Transdermal	15.8 mg
Spray	Oral	1 mg
Gum, chewing	Oral
Gum, chewing	Oral	2 G
Patch	Transdermal
Patch	Transdermal	10 MG/16ORE
Patch	Transdermal	15 MG/16ORE
Patch	Transdermal	5 MG/16ORE
Solution
Solution		10 MG
Tablet
Plaster	Transdermal	10 mg/16h
Aerosol, metered	Respiratory (inhalation)	15 mg
Plaster	Transdermal	15 mg/16h
Plaster	Transdermal	25 mg/16h
Gum, chewing; kit; paste	Dental; Oral
Gum, chewing	Buccal	2 mg
Gum, chewing	Buccal	4 mg
Lozenge	Oral	2 mg
Lozenge	Oral	4 mg
Gum, chewing	Oral	2 mg / gum
Aerosol	Respiratory (inhalation)	10 mg
Patch	Transdermal	10 mg/16hr
Patch	Transdermal	15 mg/16hr
Patch	Transdermal	25 mg/16hr
Patch	Transdermal	25 mg/16h
Patch	Transdermal	10 mg/16h
Patch, extended release	Transdermal	15.75 mg/9sq cm
Patch	Transdermal	10 mg
Patch	Transdermal	15 mg/16h
Patch, extended release	Transdermal	23.62 mg/13.5sq cm
Patch, extended release	Transdermal	39.37 mg/22.5sq cm
Patch	Transdermal	25 mg / 16 hour
Patch	Transdermal	15.75 mg
Patch	Transdermal	23.62 mg
Patch	Transdermal	39.37 mg
Patch	Transdermal	25 mg
Gum, chewing	Oral	4 mg / gum
Patch	Transdermal	10 mg/20sq cm
Patch	Transdermal	15 mg/30sq cm
Patch	Transdermal	5 mg/10sq cm
Spray	Transmucosal
Kit; lozenge	Oral
Patch	Transdermal	14 mg/24h
Patch	Transdermal	14 mg/1d
Patch	Transdermal	21 mg/1d
Patch	Transdermal	21 mg/24h
Patch	Transdermal	7 mg/24h
Patch	Transdermal	7 mg/1d
Patch	Transdermal	14 MG
Patch	Transdermal	21 MG
Patch	Transdermal	7 MG
Gum, chewing	Oral	4 mg/1
Powder	Oral	150 g/1kg
Powder	Oral	180 g/1kg
Powder	Oral	200 g/1kg
Gum, chewing	Buccal	2 mg/1
Gum, chewing	Buccal	4 mg/1
Powder	Not applicable	1 kg/1kg
Powder	Oral	1 kg/1kg
Patch	Topical
Kit	Transdermal
Patch, extended release	Topical	21 mg/24h
Patch, extended release	Transdermal	21 mg/24h
Patch, extended release	Topical	14 mg/24h
Patch, extended release	Transdermal	14 mg/24h
Patch, extended release	Topical	7 mg/24h
Liquid	Oral	1 L/1L
Tablet, extended release		2 mg
Patch	Transdermal	14 mg/24hr
Patch	Transdermal	21 mg/24hr
Patch	Transdermal	7 mg/24hr
Gum	Oral	2 mg
Gum, chewing	Oral	2.0 mg
Gum	Oral
Gum, chewing	Oral	4.0 mg
Tablet	Transmucosal
Lozenge	Oral	1 mg
Lozenge	Buccal	2 mg
Plaster	Transdermal	7 mg/24h
Patch	Transdermal	17.5 mg/10sq cm
Plaster	Transdermal	14 mg/24h
Patch	Transdermal	35 mg/20sq cm
Plaster	Transdermal	21 mg/24h
Patch	Transdermal	52.5 mg/30sq cm
Patch
Inhalant	Respiratory (inhalation)	4 mg/1
Spray, metered	Nasal	10 mg/1mL
Film	Oral	2.5 MG
Patch	Cutaneous	36.000 mg
Patch	Transdermal	14 mg/24ore
Patch	Transdermal	21 mg/24ore
Patch	Transdermal	7 mg/24ore
Tablet	Transmucosal	1.5 MG
Tablet	Transmucosal	2 MG
Tablet	Transmucosal	4 MG
Plaster	Transdermal	14 mg/24stunde
Plaster	Transdermal	21 mg/24stunde
Plaster	Transdermal	7 mg/24stunde
Patch	Transdermal	36 mg
Patch	Transdermal	78 mg
Tablet	Buccal; Oral	2 mg
Patch	Topical; Transdermal	114 mg
Gum, chewing	Oral	2 mg/1
Gum, chewing	Oral	2 mg/2h
Gum, chewing	Oral	4 mg/2h
Tablet, chewable	Oral	2 mg
Tablet, chewable	Oral	4 mg
Gum, chewing	Oral	2 mg
Gum, chewing	Oral	4 mg

Prices

Unit description	Cost	Unit
Nicotrol 168 10 mg Inhalant Inhaler	223.5USD	inhaler
Nicotine 30 21 mg/24hr Patches Box	206.52USD	box
Nicotine 30 14 mg/24hr Patches Box	196.27USD	box
Nicotrol NS 10 mg/ml Solution 10ml Bottle	55.88USD	bottle
Nicotine polacrilex powder	11.25USD	g
Nicotrol ns 10 mg/ml spray	5.37USD	ml
Nicoderm cq 21 mg/24hr patch	4.08USD	patch
Nicoderm cq 14 mg/24hr patch	3.52USD	patch
Nicoderm cq 7 mg/24hr patch	3.52USD	patch
Nicotine 11 mg/24hr patch	3.14USD	patch
Nicotine 22 mg/24hr patch	3.14USD	patch
Nicotine transdermal system	1.83USD	each
Nicotrol cartridge inhaler	1.28USD	each
Commit 2 mg lozenge	0.55USD	lozenge
Commit 4 mg lozenge	0.55USD	lozenge
Nicorette 4 mg chewing gum	0.52USD	each
Nicorette 2 mg chewing gum	0.45USD	each
Thrive nicotine 2 mg gum	0.42USD	each
Thrive nicotine 4 mg gum	0.42USD	each
CVS Pharmacy nicotine 4 mg chewing gum	0.38USD	each
CVS Pharmacy nicotine 2 mg chewing gum	0.34USD	each
Nicotine 4 mg chewing gum	0.3USD	each
Nicotine 2 mg chewing gum	0.25USD	each

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5656255	No	1997-08-12	2014-08-12
US5501236	No	1996-03-26	2010-06-08
CA1333051	No	1994-11-15	2011-11-15
US8323683	No	2012-12-04	2028-04-30
US8999379	No	2015-04-07	2020-02-13
US9205059	No	2015-12-08	2019-12-15
US8075911	No	2011-12-13	2021-05-22
US8663680	No	2014-03-04	2020-02-13
US8501164	No	2013-08-06	2029-06-14
US8940772	No	2015-01-27	2029-04-30

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	-79 °C	PhysProp
boiling point (°C)	247 °C	PhysProp
water solubility	1E+006 mg/L	SEIDELL,A (1941)
logP	1.17	HANSCH,C ET AL. (1995)
logS	0.79	ADME Research, USCD
Caco2 permeability	-4.71	ADME Research, USCD
pKa	8.5	http://www.surgeongeneral.gov/library/reports/50-years-of-progress/sgr50-chap-5.pdf

Predicted Properties

Property	Value	Source
Water Solubility	93.3 mg/mL	ALOGPS
logP	0.87	ALOGPS
logP	1.16	Chemaxon
logS	-0.24	ALOGPS
pKa (Strongest Basic)	8.58	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	2	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	16.13 Å²	Chemaxon
Rotatable Bond Count	1	Chemaxon
Refractivity	49.66 m³·mol^-1	Chemaxon
Polarizability	18.59 Å³	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	Yes	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9748
Caco-2 permeable	+	0.8867
P-glycoprotein substrate	Substrate	0.5
P-glycoprotein inhibitor I	Non-inhibitor	0.8998
P-glycoprotein inhibitor II	Non-inhibitor	0.9368
Renal organic cation transporter	Inhibitor	0.6868
CYP450 2C9 substrate	Non-substrate	0.7998
CYP450 2D6 substrate	Substrate	0.8918
CYP450 3A4 substrate	Non-substrate	0.5
CYP450 1A2 substrate	Non-inhibitor	0.6347
CYP450 2C9 inhibitor	Non-inhibitor	0.8433
CYP450 2D6 inhibitor	Non-inhibitor	0.8838
CYP450 2C19 inhibitor	Non-inhibitor	0.8543
CYP450 3A4 inhibitor	Non-inhibitor	0.8308
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.7589
Ames test	Non AMES toxic	0.9133
Carcinogenicity	Non-carcinogens	0.9626
Biodegradation	Not ready biodegradable	0.9478
Rat acute toxicity	3.4798 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.8851
hERG inhibition (predictor II)	Non-inhibitor	0.7978

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

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Spectra

Spectrum	Spectrum Type	Splash Key
GC-MS Spectrum - GC-MS	GC-MS	splash10-001i-9500000000-f2d4835c504301f9410e
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-001i-4900000000-6d65165a4417a6129eeb
GC-MS Spectrum - EI-B	GC-MS	splash10-01q9-7900000000-1e2c38b5e4e7aae10d37
GC-MS Spectrum - EI-B	GC-MS	splash10-001i-9800000000-fe889308f7088d47c31d
GC-MS Spectrum - GC-MS	GC-MS	splash10-001i-9500000000-f2d4835c504301f9410e
Mass Spectrum (Electron Ionization)	MS	splash10-001i-9400000000-47a036aa305825218fa2
MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	LC-MS/MS	splash10-00di-0900000000-3e7377f36ca2547f4885
MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	LC-MS/MS	splash10-001i-2900000000-a505fff3a4028a6f0d52
MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	LC-MS/MS	splash10-00lr-7900000000-b91a12a16d7688e8679d
MS/MS Spectrum - EI-B (HITACHI M-80) , Positive	LC-MS/MS	splash10-01q9-7900000000-10d401d7ffa1c2cdbd9f
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	LC-MS/MS	splash10-03di-0900000000-440798524836a27b78b4
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	LC-MS/MS	splash10-01q9-0900000000-926940dd7f4851dbd73b
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	LC-MS/MS	splash10-00lr-0900000000-6bccc06d40ab273cf972
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	LC-MS/MS	splash10-0159-2900000000-f7512c405bb662e040a6
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	LC-MS/MS	splash10-014i-7900000000-f1781566be5aee88f6ef
LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	LC-MS/MS	splash10-001i-0900000000-09e9b29571abf3a52e44
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-03di-0900000000-16cdb5f23105be4a892b
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-03di-0900000000-720fe01876c739a30be0
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-001i-0900000000-85a813588b57acf531fe
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-001i-0900000000-93a3dae1577f4f2dda53
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-001i-1900000000-cb6f8cec40dd9ed35d00
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-00lr-1900000000-1443b1cf22d2de281898
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-03di-0900000000-440798524836a27b78b4
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-01q9-0900000000-926940dd7f4851dbd73b
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-00lr-0900000000-6bccc06d40ab273cf972
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-0159-2900000000-1e50e1cd59e45e211535
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-014i-7900000000-f1781566be5aee88f6ef
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-001i-0900000000-09e9b29571abf3a52e44
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03di-1900000000-5c94a5e0cae203f5cc0d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03di-1900000000-7297d3409bafd5940f7b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03di-4900000000-6eb5eb6e8465f6bcc549
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-01t9-8900000000-cb7d52fa096bf9026acc
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-001i-8900000000-fc9d44dfdbf638ced593
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-016r-9000000000-6a2a9d2fab1dd0ca25a5
1H NMR Spectrum	1D NMR	Not Applicable
1H NMR Spectrum	1D NMR	Not Applicable
13C NMR Spectrum	1D NMR	Not Applicable
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable
[1H,1H] 2D NMR Spectrum	2D NMR	Not Applicable
[1H,13C] 2D NMR Spectrum	2D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	137.2553359	predicted	DarkChem Lite v0.1.0
[M-H]-	137.7063359	predicted	DarkChem Lite v0.1.0
[M-H]-	137.6019359	predicted	DarkChem Lite v0.1.0
[M-H]-	132.68898	predicted	DeepCCS 1.0 (2019)
[M+H]+	138.5525359	predicted	DarkChem Lite v0.1.0
[M+H]+	138.2663359	predicted	DarkChem Lite v0.1.0
[M+H]+	138.6181359	predicted	DarkChem Lite v0.1.0
[M+H]+	135.03639	predicted	DeepCCS 1.0 (2019)
[M+Na]+	137.6425359	predicted	DarkChem Lite v0.1.0
[M+Na]+	138.0374359	predicted	DarkChem Lite v0.1.0
[M+Na]+	137.8634359	predicted	DarkChem Lite v0.1.0
[M+Na]+	142.47316	predicted	DeepCCS 1.0 (2019)

Targets

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Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	4700	N/A	N/A	A27354
EC 50 (nM)	6600	N/A	N/A	A27355

Details1. Neuronal acetylcholine receptor subunit alpha-4

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions
Specific Function: acetylcholine binding
Gene Name: CHRNA4
Uniprot ID: P43681
Uniprot Name: Neuronal acetylcholine receptor subunit alpha-4
Molecular Weight: 69956.47 Da

References

Espeseth T, Endestad T, Rootwelt H, Reinvang I: Nicotine receptor gene CHRNA4 modulates early event-related potentials in auditory and visual oddball target detection tasks. Neuroscience. 2007 Jul 29;147(4):974-85. Epub 2007 Jun 27. [Article]
Winterer G, Musso F, Konrad A, Vucurevic G, Stoeter P, Sander T, Gallinat J: Association of attentional network function with exon 5 variations of the CHRNA4 gene. Hum Mol Genet. 2007 Sep 15;16(18):2165-74. Epub 2007 Jul 5. [Article]
Ehringer MA, Clegg HV, Collins AC, Corley RP, Crowley T, Hewitt JK, Hopfer CJ, Krauter K, Lessem J, Rhee SH, Schlaepfer I, Smolen A, Stallings MC, Young SE, Zeiger JS: Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine. Am J Med Genet B Neuropsychiatr Genet. 2007 Jul 5;144B(5):596-604. [Article]
Klaassen A, Glykys J, Maguire J, Labarca C, Mody I, Boulter J: Seizures and enhanced cortical GABAergic inhibition in two mouse models of human autosomal dominant nocturnal frontal lobe epilepsy. Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19152-7. Epub 2006 Dec 4. [Article]
De Luca V, Voineskos S, Wong G, Kennedy JL: Genetic interaction between alpha4 and beta2 subunits of high affinity nicotinic receptor: analysis in schizophrenia. Exp Brain Res. 2006 Sep;174(2):292-6. Epub 2006 Apr 25. [Article]
Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Details2. Neuronal acetylcholine receptor subunit alpha-7

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin
Specific Function: acetylcholine binding
Gene Name: CHRNA7
Uniprot ID: P36544
Uniprot Name: Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight: 56448.925 Da

References

Mexal S, Jenkins PM, Lautner MA, Iacob E, Crouch EL, Stitzel JA: alpha7 nicotinic receptor gene promoter polymorphisms in inbred mice affect expression in a cell type-specific fashion. J Biol Chem. 2007 May 4;282(18):13220-7. Epub 2007 Mar 14. [Article]
Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R: Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry. 2006 Jun;63(6):630-8. [Article]
Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	4000	N/A	N/A	A27356
EC 50 (nM)	5000	N/A	N/A	A27357
EC 50 (nM)	132000	N/A	N/A	A27370
EC 50 (nM)	9400	N/A	N/A	A27372
EC 50 (nM)	6600	N/A	N/A	A27373
EC 50 (nM)	300	N/A	N/A	A27376
EC 50 (nM)	290	N/A	N/A	A27377 / A27378
EC 50 (nM)	1	N/A	N/A	A27380
EC 50 (nM)	3000	N/A	N/A	A27381
EC 50 (nM)	295	N/A	N/A	A27382
EC 50 (nM)	295.12	N/A	N/A	A27382
EC 50 (nM)	2400	N/A	N/A	A27384
IC 50 (nM)	430	N/A	N/A	A27376 / A27377 / A27378
IC 50 (nM)	427	N/A	N/A	A27382
IC 50 (nM)	426.58	N/A	N/A	A27382
IC 50 (nM)	370	N/A	N/A	A27384
Ki (nM)	4	N/A	N/A	A27358
Ki (nM)	2.3	N/A	N/A	A27359
Ki (nM)	1.26	N/A	N/A	A27360
Ki (nM)	1.5	N/A	N/A	A27360 / A27374
Ki (nM)	1.01	N/A	N/A	A27360
Ki (nM)	2	N/A	N/A	A27361 / A27365 / A27381 / A27383
Ki (nM)	1.4	N/A	N/A	A27362
Ki (nM)	9.1	N/A	N/A	A27363
Ki (nM)	2.1	N/A	N/A	A27364
Ki (nM)	1.2	N/A	N/A	A27366
Ki (nM)	47	N/A	N/A	A27367
Ki (nM)	>10000	N/A	N/A	A27368
Ki (nM)	1.6	N/A	N/A	A27369 / A27371
Ki (nM)	9.46	N/A	N/A	A27375
Ki (nM)	12.59	N/A	N/A	A27379
Ki (nM)	4.9	N/A	N/A	A27382
Ki (nM)	5.5	N/A	N/A	A27382

Details3. Neuronal acetylcholine receptor subunit beta-2

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodiun ions
Specific Function: acetylcholine binding
Gene Name: CHRNB2
Uniprot ID: P17787
Uniprot Name: Neuronal acetylcholine receptor subunit beta-2
Molecular Weight: 57018.575 Da

References

Ehringer MA, Clegg HV, Collins AC, Corley RP, Crowley T, Hewitt JK, Hopfer CJ, Krauter K, Lessem J, Rhee SH, Schlaepfer I, Smolen A, Stallings MC, Young SE, Zeiger JS: Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine. Am J Med Genet B Neuropsychiatr Genet. 2007 Jul 5;144B(5):596-604. [Article]
De Luca V, Voineskos S, Wong G, Kennedy JL: Genetic interaction between alpha4 and beta2 subunits of high affinity nicotinic receptor: analysis in schizophrenia. Exp Brain Res. 2006 Sep;174(2):292-6. Epub 2006 Apr 25. [Article]
Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	9900	N/A	N/A	A20290

Details4. Neuronal acetylcholine receptor subunit alpha-2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane
Specific Function: acetylcholine receptor activity
Gene Name: CHRNA2
Uniprot ID: Q15822
Uniprot Name: Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight: 59764.82 Da

References

Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]
Sullivan PF, Neale BM, van den Oord E, Miles MF, Neale MC, Bulik CM, Joyce PR, Straub RE, Kendler KS: Candidate genes for nicotine dependence via linkage, epistasis, and bioinformatics. Am J Med Genet B Neuropsychiatr Genet. 2004 Apr 1;126B(1):23-36. [Article]

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	9400	N/A	N/A	A27354
Ki (nM)	220	N/A	N/A	A27359

Details5. Neuronal acetylcholine receptor subunit alpha-3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane
Specific Function: acetylcholine binding
Gene Name: CHRNA3
Uniprot ID: P32297
Uniprot Name: Neuronal acetylcholine receptor subunit alpha-3
Molecular Weight: 57479.54 Da

References

Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Details6. Neuronal acetylcholine receptor subunit alpha-5

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane
Specific Function: acetylcholine receptor activity
Gene Name: CHRNA5
Uniprot ID: P30532
Uniprot Name: Neuronal acetylcholine receptor subunit alpha-5
Molecular Weight: 53053.965 Da

References

Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Details7. Neuronal acetylcholine receptor subunit alpha-6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane
Specific Function: acetylcholine receptor activity
Gene Name: CHRNA6
Uniprot ID: Q15825
Uniprot Name: Neuronal acetylcholine receptor subunit alpha-6
Molecular Weight: 56897.745 Da

References

Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Details8. Neuronal acetylcholine receptor subunit alpha-9

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding induces a conformation change that leads to the opening of an ion-conducting channel across the plasma membrane (PubMed:11752216, PubMed:25282151). The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane (PubMed:11752216, PubMed:25282151). In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma. May also regulate keratinocyte adhesion (PubMed:11021840)
Specific Function: acetylcholine-gated monoatomic cation-selective channel activity
Gene Name: CHRNA9
Uniprot ID: Q9UGM1
Uniprot Name: Neuronal acetylcholine receptor subunit alpha-9
Molecular Weight: 54806.63 Da

References

Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Details9. Neuronal acetylcholine receptor subunit alpha-10

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma
Specific Function: acetylcholine-gated monoatomic cation-selective channel activity
Gene Name: CHRNA10
Uniprot ID: Q9GZZ6
Uniprot Name: Neuronal acetylcholine receptor subunit alpha-10
Molecular Weight: 49704.295 Da

References

Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Details10. Neuronal acetylcholine receptor subunit beta-3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane
Specific Function: acetylcholine binding
Gene Name: CHRNB3
Uniprot ID: Q05901
Uniprot Name: Neuronal acetylcholine receptor subunit beta-3
Molecular Weight: 52728.215 Da

References

Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	4300	N/A	N/A	A27363
Ki (nM)	320	N/A	N/A	A27363
Ki (nM)	129	N/A	N/A	A27363

Details11. Neuronal acetylcholine receptor subunit beta-4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane
Specific Function: acetylcholine receptor activity
Gene Name: CHRNB4
Uniprot ID: P30926
Uniprot Name: Neuronal acetylcholine receptor subunit beta-4
Molecular Weight: 56378.985 Da

References

Mansvelder HD, Mertz M, Role LW: Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol. 2009 Jun;20(4):432-40. doi: 10.1016/j.semcdb.2009.01.007. Epub 2009 Jan 22. [Article]
Narahashi T, Fenster CP, Quick MW, Lester RA, Marszalec W, Aistrup GL, Sattelle DB, Martin BR, Levin ED: Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol Sci. 2000 Oct;57(2):193-202. [Article]
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI: Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther. 2010 Jul;334(1):137-46. doi: 10.1124/jpet.110.165738. Epub 2010 Apr 16. [Article]
Zaniewska M, Przegalinski E, Filip M: Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Pharmacol Rep. 2009 Nov-Dec;61(6):957-65. [Article]

Details12. Aromatase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (PubMed:27702664, PubMed:2848247). Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid (PubMed:20385561). Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen (PubMed:22773874). Also displays 2-hydroxylase activity toward estrone (PubMed:22773874). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:20385561, PubMed:22773874)
Specific Function: aromatase activity
Gene Name: CYP19A1
Uniprot ID: P11511
Uniprot Name: Aromatase
Molecular Weight: 57882.48 Da

References

Barbieri RL, Gochberg J, Ryan KJ: Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro. J Clin Invest. 1986 Jun;77(6):1727-33. [Article]

Details13. Choline O-acetyltransferase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses
Specific Function: choline O-acetyltransferase activity
Gene Name: CHAT
Uniprot ID: P28329
Uniprot Name: Choline O-acetyltransferase
Molecular Weight: 82535.025 Da

References

FAHMY AR, RYMAN BE, WALSH EO: The inhibition of choline acetylase by nicotine. J Pharm Pharmacol. 1954 Sep;6(9):607-9. [Article]

Enzymes

Details1. Cytochrome P450 1A1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inducer

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
Specific Function: arachidonic acid monooxygenase activity
Gene Name: CYP1A1
Uniprot ID: P04798
Uniprot Name: Cytochrome P450 1A1
Molecular Weight: 58164.815 Da

References

Wei C, Caccavale RJ, Weyand EH, Chen S, Iba MM: Induction of CYP1A1 and CYP1A2 expressions by prototypic and atypical inducers in the human lung. Cancer Lett. 2002 Apr 8;178(1):25-36. [Article]
Zevin S, Benowitz NL: Drug interactions with tobacco smoking. An update. Clin Pharmacokinet. 1999 Jun;36(6):425-38. doi: 10.2165/00003088-199936060-00004. [Article]
Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	4100000	N/A	N/A	A27385

Details2. Cytochrome P450 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inducer
Curator comments: Nicotine has been shown to be a CYP1A2 substrate when it is present in high concentrations.

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function: aromatase activity
Gene Name: CYP1A2
Uniprot ID: P05177
Uniprot Name: Cytochrome P450 1A2
Molecular Weight: 58406.915 Da

References

Hukkanen J, Jacob P 3rd, Peng M, Dempsey D, Benowitz NL: Effect of nicotine on cytochrome P450 1A2 activity. Br J Clin Pharmacol. 2011 Nov;72(5):836-8. doi: 10.1111/j.1365-2125.2011.04023.x. [Article]
Zevin S, Benowitz NL: Drug interactions with tobacco smoking. An update. Clin Pharmacokinet. 1999 Jun;36(6):425-38. doi: 10.2165/00003088-199936060-00004. [Article]
Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]
Pal D, Kwatra D, Minocha M, Paturi DK, Budda B, Mitra AK: Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals. Life Sci. 2011 May 23;88(21-22):959-71. doi: 10.1016/j.lfs.2010.09.012. Epub 2010 Nov 1. [Article]

Details3. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
Specific Function: (R)-limonene 6-monooxygenase activity
Gene Name: CYP2C19
Uniprot ID: P33261
Uniprot Name: Cytochrome P450 2C19
Molecular Weight: 55944.565 Da

References

Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]

Details4. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function: arachidonic acid epoxygenase activity
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]

Details5. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Curator comments: Nicotine has been shown to be a substrate of CYP2C9 when it is present in high concentrations. Clinical correlation is unknown.

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function: (R)-limonene 6-monooxygenase activity
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]

Details6. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function: anandamide 11,12 epoxidase activity
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]
Benowitz NL, Jacob P 3rd, Perez-Stable E: CYP2D6 phenotype and the metabolism of nicotine and cotinine. Pharmacogenetics. 1996 Jun;6(3):239-42. [Article]
Tiili EM, Antikainen MS, Mitiushkina NV, Sukhovskaya OA, Imyanitov EN, Hirvonen AP: Effect of genotype and methylation of CYP2D6 on smoking behaviour. Pharmacogenet Genomics. 2015 Nov;25(11):531-40. doi: 10.1097/FPC.0000000000000166. [Article]

Details7. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function: 1,8-cineole 2-exo-monooxygenase activity
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]

Details8. Amine oxidase [flavin-containing] A

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:18391214, PubMed:20493079, PubMed:24169519, PubMed:8316221). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity)
Specific Function: aliphatic amine oxidase activity
Gene Name: MAOA
Uniprot ID: P21397
Uniprot Name: Amine oxidase [flavin-containing] A
Molecular Weight: 59681.27 Da

References

Lewis AJ, Truman P, Hosking MR, Miller JH: Monoamine oxidase inhibitory activity in tobacco smoke varies with tobacco type. Tob Control. 2012 Jan;21(1):39-43. doi: 10.1136/tc.2010.040287. Epub 2011 Jun 2. [Article]
Leroy C, Bragulat V, Berlin I, Gregoire MC, Bottlaender M, Roumenov D, Dolle F, Bourgeois S, Penttila J, Artiges E, Martinot JL, Trichard C: Cerebral monoamine oxidase A inhibition in tobacco smokers confirmed with PET and [11C]befloxatone. J Clin Psychopharmacol. 2009 Feb;29(1):86-8. doi: 10.1097/JCP.0b013e31819e98f. [Article]

Details9. Amine oxidase [flavin-containing] B

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924). Preferentially degrades benzylamine and phenylethylamine (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924)
Specific Function: aliphatic amine oxidase activity
Gene Name: MAOB
Uniprot ID: P27338
Uniprot Name: Amine oxidase [flavin-containing] B
Molecular Weight: 58762.475 Da

References

Lewis AJ, Truman P, Hosking MR, Miller JH: Monoamine oxidase inhibitory activity in tobacco smoke varies with tobacco type. Tob Control. 2012 Jan;21(1):39-43. doi: 10.1136/tc.2010.040287. Epub 2011 Jun 2. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	580000	N/A	N/A	A27386

Details10. Cytochrome P450 2A6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity
Specific Function: arachidonic acid epoxygenase activity
Gene Name: CYP2A6
Uniprot ID: P11509
Uniprot Name: Cytochrome P450 2A6
Molecular Weight: 56517.005 Da

References

Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]
von Weymarn LB, Retzlaff C, Murphy SE: CYP2A6- and CYP2A13-catalyzed metabolism of the nicotine Delta5'(1')iminium ion. J Pharmacol Exp Ther. 2012 Nov;343(2):307-15. doi: 10.1124/jpet.112.195255. Epub 2012 Aug 6. [Article]
Raunio H, Rautio A, Gullsten H, Pelkonen O: Polymorphisms of CYP2A6 and its practical consequences. Br J Clin Pharmacol. 2001 Oct;52(4):357-63. [Article]
Denton TT, Zhang X, Cashman JR: Nicotine-related alkaloids and metabolites as inhibitors of human cytochrome P-450 2A6. Biochem Pharmacol. 2004 Feb 15;67(4):751-6. [Article]

Details11. Cytochrome P450 2E1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer
Curator comments: References provide evidence mainly through in vitro tests. The actual role and strength of the interaction of nicotine on CYP2E1 is unclear.

General Function: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
Specific Function: 4-nitrophenol 2-monooxygenase activity
Gene Name: CYP2E1
Uniprot ID: P05181
Uniprot Name: Cytochrome P450 2E1
Molecular Weight: 56848.42 Da

References

Howard LA, Miksys S, Hoffmann E, Mash D, Tyndale RF: Brain CYP2E1 is induced by nicotine and ethanol in rat and is higher in smokers and alcoholics. Br J Pharmacol. 2003 Apr;138(7):1376-86. doi: 10.1038/sj.bjp.0705146. [Article]
Van Vleet TR, Bombick DW, Coulombe RA Jr: Inhibition of human cytochrome P450 2E1 by nicotine, cotinine, and aqueous cigarette tar extract in vitro. Toxicol Sci. 2001 Dec;64(2):185-91. [Article]
Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]
Micu AL, Miksys S, Sellers EM, Koop DR, Tyndale RF: Rat hepatic CYP2E1 is induced by very low nicotine doses: an investigation of induction, time course, dose response, and mechanism. J Pharmacol Exp Ther. 2003 Sep;306(3):941-7. doi: 10.1124/jpet.103.052183. Epub 2003 May 15. [Article]
Hukkanen J, Jacob Iii P, Peng M, Dempsey D, Benowitz NL: Effects of nicotine on cytochrome P450 2A6 and 2E1 activities. Br J Clin Pharmacol. 2010 Feb;69(2):152-9. doi: 10.1111/j.1365-2125.2009.03568.x. [Article]
Nakayama H, Okuda H, Nakashima T, Imaoka S, Funae Y: Nicotine metabolism by rat hepatic cytochrome P450s. Biochem Pharmacol. 1993 Jun 22;45(12):2554-6. [Article]

Details12. Cytochrome P450 2A13

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity
Specific Function: arachidonic acid epoxygenase activity
Gene Name: CYP2A13
Uniprot ID: Q16696
Uniprot Name: Cytochrome P450 2A13
Molecular Weight: 56687.095 Da

References

von Weymarn LB, Brown KM, Murphy SE: Inactivation of CYP2A6 and CYP2A13 during nicotine metabolism. J Pharmacol Exp Ther. 2006 Jan;316(1):295-303. doi: 10.1124/jpet.105.091306. Epub 2005 Sep 27. [Article]
He XY, Shen J, Hu WY, Ding X, Lu AY, Hong JY: Identification of Val117 and Arg372 as critical amino acid residues for the activity difference between human CYP2A6 and CYP2A13 in coumarin 7-hydroxylation. Arch Biochem Biophys. 2004 Jul 15;427(2):143-53. doi: 10.1016/j.abb.2004.03.016. [Article]
Bao Z, He XY, Ding X, Prabhu S, Hong JY: Metabolism of nicotine and cotinine by human cytochrome P450 2A13. Drug Metab Dispos. 2005 Feb;33(2):258-61. doi: 10.1124/dmd.104.002105. Epub 2004 Nov 4. [Article]

Details13. Cytochrome P450 2B6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
Specific Function: anandamide 11,12 epoxidase activity
Gene Name: CYP2B6
Uniprot ID: P20813
Uniprot Name: Cytochrome P450 2B6
Molecular Weight: 56277.81 Da

References

Yamazaki H, Inoue K, Hashimoto M, Shimada T: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70. [Article]
Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]

Transporters

Details1. Solute carrier family 22 member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function: acetylcholine transmembrane transporter activity
Gene Name: SLC22A2
Uniprot ID: O15244
Uniprot Name: Solute carrier family 22 member 2
Molecular Weight: 62579.99 Da

References

Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [Article]
Urakami Y, Okuda M, Masuda S, Saito H, Inui KI: Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther. 1998 Nov;287(2):800-5. [Article]
Okuda M, Urakami Y, Saito H, Inui K: Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim Biophys Acta. 1999 Mar 4;1417(2):224-31. [Article]

Details2. Solute carrier family 22 member 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
Specific Function: (R)-carnitine transmembrane transporter activity
Gene Name: SLC22A1
Uniprot ID: O15245
Uniprot Name: Solute carrier family 22 member 1
Molecular Weight: 61153.345 Da

References

Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [Article]
Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. [Article]
Urakami Y, Okuda M, Masuda S, Saito H, Inui KI: Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther. 1998 Nov;287(2):800-5. [Article]

Details3. Solute carrier family 22 member 3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity)
Specific Function: monoamine transmembrane transporter activity
Gene Name: SLC22A3
Uniprot ID: O75751
Uniprot Name: Solute carrier family 22 member 3
Molecular Weight: 61279.485 Da

References

Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, Ganapathy V: Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem. 1998 Jun 26;273(26):15971-9. [Article]

Details4. Organic cation/carnitine transporter 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, PubMed:33124720). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from Bacillus Subtilis wich induces cytoprotective heat shock proteins contributing to intestinal homeostasis (PubMed:18005709). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function: (R)-carnitine transmembrane transporter activity
Gene Name: SLC22A5
Uniprot ID: O76082
Uniprot Name: Organic cation/carnitine transporter 2
Molecular Weight: 62751.08 Da

References

Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. [Article]
Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [Article]
Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. [Article]

Details5. Solute carrier family 22 member 4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:10215651, PubMed:15107849, PubMed:15795384, PubMed:16729965, PubMed:20601551, PubMed:22206629, PubMed:22569296, PubMed:29530864). Functions as a Na(+)-dependent and pH-dependent high affinity microbial symporter of potent food-derived antioxidant ergothioeine (PubMed:15795384, PubMed:29530864, PubMed:33124720). Transports one sodium ion with one ergothioeine molecule (By similarity). Involved in the absorption of ergothioneine from the luminal/apical side of the small intestine and renal tubular cells, and into non-parenchymal liver cells, thereby contributing to maintain steady-state ergothioneine level in the body (PubMed:20601551). Also mediates the bidirectional transport of acetycholine, although the exact transport mechanism has not been fully identified yet (PubMed:22206629). Most likely exports anti-inflammatory acetylcholine in non-neuronal tissues, thereby contributing to the non-neuronal cholinergic system (PubMed:22206629, PubMed:22569296). Displays a general physiological role linked to better survival by controlling inflammation and oxidative stress, which may be related to ergothioneine and acetycholine transports (PubMed:15795384, PubMed:22206629). May also function as a low-affinity Na(+)-dependent transporter of L-carnitine through the mitochondrial membrane, thereby maintaining intracellular carnitine homeostasis (PubMed:10215651, PubMed:15107849, PubMed:16729965). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (PubMed:35307651)
Specific Function: acetylcholine transmembrane transporter activity
Gene Name: SLC22A4
Uniprot ID: Q9H015
Uniprot Name: Solute carrier family 22 member 4
Molecular Weight: 62154.48 Da

References

Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [Article]
Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V: Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315-27. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 10, 2024 12:49

Nicotine

Identification

Structure for Nicotine (DB00184)

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Clinical Trial & Rare Diseases Add-on Data Package

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Enzymes

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