Identification

Name
Cimetidine
Accession Number
DB00501  (APRD00568)
Type
Small Molecule
Groups
Approved, Investigational
Description

A histamine congener, it competitively inhibits histamine binding to histamine H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrins output. It also blocks the activity of cytochrome P-450 which might explain proposals for use in neoadjuvant therapy. [PubChem]

Structure
Thumb
Synonyms
  • 1-Cyano-2-methyl-3-(2-(((5-methyl-4-imidazolyl)methyl)thio)ethyl)guanidine
  • 2-Cyano-1-methyl-3-(2-(((5-methylimidazol-4-yl)methyl)thio)ethyl)guanidine
  • Cimetag
  • Cimetidin
  • Cimetidina
  • Cimétidine
  • Cimetidinum
  • N-Cyano-n'-methyl-n''-(2-([(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl)ethyl)guanidine
  • N''-cyano-N-methyl-n'-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]thio}ethyl)guanidine
  • Tagamet hb 200
  • Ulcerfen
External IDs
NSC-335308 / SKF 92334 / SKF-92334
Product Ingredients
IngredientUNIICASInChI Key
Cimetidine HydrochlorideWF1049167370059-30-2QJHCNBWLPSXHBL-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo Cimetidine Tab 200mgTablet200 mgOralApotex Corporation1982-12-31Not applicableCanada
Apo Cimetidine Tab 300mgTablet300 mgOralApotex Corporation1982-12-31Not applicableCanada
Apo Cimetidine Tab 400mgTablet400 mgOralApotex Corporation1983-12-31Not applicableCanada
Apo Cimetidine Tab 600mgTablet600 mgOralApotex Corporation1983-12-31Not applicableCanada
CimetidineTablet, film coated200 mg/1OralTEVA PHARMACEUTICALS USA2006-11-282006-11-28Us
Cimetidine 200 Tab 200mgTablet200 mgOralPro Doc Limitee1984-12-312009-07-23Canada
Cimetidine in Sodium ChlorideInjection, solution6 mg/1mLIntravenousHospira, Inc.2006-04-13Not applicableUs
Cimetidine Tab 300mgTablet300 mgOralPro Doc Limitee1983-12-312010-07-13Canada
Cimetidine Tab 400mgTablet400 mgOralPro Doc Limitee1984-12-312009-07-23Canada
Cimetidine Tab 600mgTablet600 mgOralPro Doc Limitee1984-12-312012-07-23Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-cimetidine Oral SolutionLiquid300 mgOralApotex Corporation2001-01-05Not applicableCanada
Apo-cimetidine Tab 800mgTablet800 mgOralApotex Corporation1988-12-31Not applicableCanada
CimetidineTablet, film coated300 mg/1OralBlenheim Pharmacal, Inc.2014-01-14Not applicableUs
CimetidineTablet, film coated300 mg/1OralRemedy Repack2013-03-142014-03-14Us00093 8192 01 nlmimage10 39361ce0
CimetidineTablet, film coated200 mg/1OralMylan Pharmaceuticals Inc.1994-05-17Not applicableUs
CimetidineTablet400 mg/1OralRebel Distributors2010-11-24Not applicableUs
CimetidineTablet, film coated400 mg/1OralPreferreed Pharmaceuticals Inc.2011-07-06Not applicableUs68788 906420180913 8702 1az3vta
CimetidineTablet, film coated300 mg/1OralIVAX Pharmaceuticals, Inc.1995-06-292012-03-31Us
CimetidineTablet, film coated400 mg/1OralAidarex Pharmaceuticals LLC2004-02-02Not applicableUs
CimetidineTablet, film coated300 mg/1Oralbryant ranch prepack2003-11-24Not applicableUs63629 178320180907 15195 dxf6ws
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Acid ReducerTablet200 mg/1OralRite Aid2005-07-082014-07-27Us
Acid ReducerTablet200 mg/1OralKroger2015-10-21Not applicableUs
Cimetidine Acid ReducerTablet200 mg/1OralWalgreen2001-03-27Not applicableUs
DG Health Heartburn ReliefTablet200 mg/1OralDolgencorp2010-03-022014-08-18Us
Equaline Acid ReducerTablet200 mg/1OralSupervalu2004-09-152014-11-01Us
Equate CimetidineTablet200 mg/1OralWalmart Stores2006-09-27Not applicableUs
Gaviscon All-nightTablet100 mgOralGlaxosmithkline IncNot applicableNot applicableCanada
Gaviscon PreventTablet100 mgOralGlaxosmithkline Inc1998-08-172002-07-31Canada
Gaviscon Prevent Extra StrengthTablet200 mgOralGlaxosmithkline IncNot applicableNot applicableCanada
Good Neighbor Pharmacy Heartburn ReliefTablet200 mg/1OralAmerisource Bergen2000-01-05Not applicableUs
International/Other Brands
Cimetag (Julphar) / Tagamet HB200 (GlaxoSmithKline) / Ulcedine / Ulcerfen (Finadiet) / Ulcimet (Farmasa)
Categories
UNII
80061L1WGD
CAS number
51481-61-9
Weight
Average: 252.339
Monoisotopic: 252.115715232
Chemical Formula
C10H16N6S
InChI Key
AQIXAKUUQRKLND-UHFFFAOYSA-N
InChI
InChI=1S/C10H16N6S/c1-8-9(16-7-15-8)5-17-4-3-13-10(12-2)14-6-11/h7H,3-5H2,1-2H3,(H,15,16)(H2,12,13,14)
IUPAC Name
(Z)-1-cyano-2-methyl-3-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl)guanidine
SMILES
C\N=C(\NCCSCC1=C(C)NC=N1)NC#N

Pharmacology

Indication

For the treatment and the management of acid-reflux disorders (GERD), peptic ulcer disease, heartburn, and acid indigestion.

Associated Conditions
Pharmacodynamics

Cimetidine is a histamine H2-receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. It is used to treat gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. Cimetidine inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Cimetidine include an increase in gastric bacterial flora such as nitrate-reducing organisms.

Mechanism of action

Cimetidine binds to an H2-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity.

TargetActionsOrganism
AHistamine H2 receptor
antagonist
Human
Absorption

Rapid 60-70%

Volume of distribution
Not Available
Protein binding

15-20%

Metabolism

Hepatic

Route of elimination

The principal route of excretion of cimetidine is the urine.

Half life

2 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include nausea, vomiting, diarrhea, increased saliva production, difficulty breathing, and a fast heartbeat.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Cimetidine Action PathwayDrug action
Cimetidine Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Cimetidine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Cimetidine.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Cimetidine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Cimetidine.
3-isobutyl-1-methyl-7H-xanthineThe metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Cimetidine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Cimetidine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Cimetidine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Cimetidine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Cimetidine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Cimetidine.
Food Interactions
  • Avoid alcohol.
  • Best effect when taken with food.
  • Limit caffeine intake.

References

Synthesis Reference

Saburo Uchikuga, Tomoyasu Tashiro, Yasuko Osawa, "Process for preparing the H.sub.2 -receptor antagonist cimetidine." U.S. Patent US4413129, issued March, 1972.

US4413129
General References
  1. Michnovicz JJ, Galbraith RA: Cimetidine inhibits catechol estrogen metabolism in women. Metabolism. 1991 Feb;40(2):170-4. [PubMed:1988774]
External Links
Human Metabolome Database
HMDB0014644
KEGG Drug
D00295
KEGG Compound
C06952
PubChem Compound
2756
PubChem Substance
46505360
ChemSpider
2654
BindingDB
22889
ChEBI
3699
ChEMBL
CHEMBL30
Therapeutic Targets Database
DAP000338
PharmGKB
PA449001
IUPHAR
1231
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cimetidine
ATC Codes
A02BA01 — CimetidineA02BA51 — Cimetidine, combinations
AHFS Codes
  • 56:28.12 — Histamine H2-antagonists
FDA label
Download (420 KB)
MSDS
Download (73.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedOtherDrug Drug Interaction (DDI) / Healthy Volunteers / Pharmacokinetics1
1CompletedOtherHealthy Volunteers2
1CompletedTreatmentHealthy Volunteers2
1TerminatedNot AvailableGeneralized Anxiety Disorder (GAD)1
1Unknown StatusBasic ScienceHealthy Volunteers1
2CompletedTreatmentEndometrial Cancers1
2CompletedTreatmentMelanoma (Skin) / Renal Cancers / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedPreventionPeptic ulcer haemorrhage1
3CompletedPreventionStress Ulcer Prophylaxis1
3CompletedPreventionUpper Gastrointestinal Hemorrhage1
Not AvailableCompletedNot AvailableCommunity Acquired Pneumonia (CAP) / Gastro-esophageal Reflux Disease (GERD)1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
  • Apotex inc
  • Contract pharmacal corp
  • Dava pharmaceuticals inc
  • Endo pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lek pharmaceuticals d d
  • Mylan pharmaceuticals inc
  • L perrigo co
  • Perrigo co
  • Pliva inc
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Teva parenteral medicines inc
  • Actavis mid atlantic llc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Hi tech pharmacal co inc
  • Novex pharma
  • Pharmaceutical assoc inc div beach products
  • Teva pharmaceuticals usa
  • Wockhardt eu operations (swiss) ag
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Baxter International Inc.
  • Bristol-Myers Squibb Co.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Central Texas Community Health Centers
  • Comprehensive Consultant Services Inc.
  • Darby Dental Supply Co. Inc.
  • DAVA Pharmaceuticals
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Endo Pharmaceuticals Inc.
  • GlaxoSmithKline Inc.
  • Group Health Cooperative
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hi Tech Pharmacal Co. Inc.
  • Hospira Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Lek Pharmaceuticals Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novex Pharma
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Perrigo Co.
  • Pharma Pac LLC
  • Pharmaceutical Association
  • Pharmedix
  • Pharmpak Inc.
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescription Dispensing Service Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Sandhills Packaging Inc.
  • Sanofi-Aventis Inc.
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
TabletOral200 mg
TabletOral300 mg
TabletOral600 mg
TabletOral300 mg/1
TabletOral400 mg/1
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral300 mg/1
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral800 mg/1
Injection, solutionIntramuscular; Intravenous150 mg/1mL
SolutionOral300 mg/5mL
Injection, solutionIntravenous6 mg/1mL
TabletOral100 mg
SolutionIntramuscular; Intravenous150 mg
TabletOral400 mg
TabletOral800 mg
TabletOral200 mg/1
LiquidIntravenous6 mg
LiquidIntramuscular; Intravenous150 mg
LiquidOral300 mg
LiquidOral60 mg
Prices
Unit descriptionCostUnit
Cimetidine 800 mg tablet2.7USD tablet
Tagamet 400 mg tablet2.51USD tablet
Cimetidine 150 mg/ml vial1.67USD ml
Cimetidine powder1.48USD g
Cimetidine 400 mg tablet1.44USD tablet
Tagamet 300 mg tablet1.28USD tablet
Cimetidine 300 mg tablet0.93USD tablet
Cimetidine 200 mg tablet0.46USD tablet
Cimetidine HCl 300 mg/5ml Solution0.38USD ml
Tagamet hb 200 mg tablet0.37USD tablet
Apo-Cimetidine 800 mg Tablet0.27USD tablet
Mylan-Cimetidine 800 mg Tablet0.27USD tablet
Acid reducer 200 mg tablet0.21USD tablet
Apo-Cimetidine 600 mg Tablet0.18USD tablet
Mylan-Cimetidine 600 mg Tablet0.18USD tablet
Novo-Cimetine 600 mg Tablet0.18USD tablet
Nu-Cimet 600 mg Tablet0.18USD tablet
Apo-Cimetidine 400 mg Tablet0.14USD tablet
Mylan-Cimetidine 400 mg Tablet0.14USD tablet
Novo-Cimetine 400 mg Tablet0.14USD tablet
Nu-Cimet 400 mg Tablet0.14USD tablet
Apo-Cimetidine 200 mg Tablet0.09USD tablet
Apo-Cimetidine 300 mg Tablet0.09USD tablet
Mylan-Cimetidine 300 mg Tablet0.09USD tablet
Novo-Cimetine 300 mg Tablet0.09USD tablet
Nu-Cimet 300 mg Tablet0.09USD tablet
Heartburn relief 200 mg tablet0.08USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)142 °CPhysProp
water solubility9380 mg/L (at 25 °C)MCFARLAND,JW ET AL. (2001)
logP0.40HANSCH,C ET AL. (1995)
logS-1.35ADME Research, USCD
Caco2 permeability-5.89ADME Research, USCD
pKa6.8TOMLINSON,E & HAFKENSCHEID,TL (1986)
Predicted Properties
PropertyValueSource
Water Solubility0.816 mg/mLALOGPS
logP0.44ALOGPS
logP-0.11ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)13.38ChemAxon
pKa (Strongest Basic)6.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area88.89 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity70.32 m3·mol-1ChemAxon
Polarizability27.47 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9855
Blood Brain Barrier-0.6782
Caco-2 permeable-0.6358
P-glycoprotein substrateSubstrate0.7887
P-glycoprotein inhibitor INon-inhibitor0.8781
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterInhibitor0.7233
CYP450 2C9 substrateNon-substrate0.8048
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5795
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.5773
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9575
Ames testNon AMES toxic0.837
CarcinogenicityNon-carcinogens0.9579
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.7341 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7983
hERG inhibition (predictor II)Non-inhibitor0.8745
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-002b-9510000000-36ce01132725fd5bf5d8
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4j-5900000000-122f9dbdf583bbe3dee8
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-9300000000-39ee157d9e264867cfa4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-9000000000-6e876a668444c8277412
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-9000000000-85640be9b2799889fd02
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-9000000000-9b8d3eafde213bee6396
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4j-9000000000-b47e11697992a843f5e4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-9000000000-75ebe86c90f5ed341c57
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0aor-9000000000-d7302885bef7454b4db2
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-9000000000-b2f3ab1b5ae1e2f8f8bb
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-0930000000-dbae8348b5c999cc664d
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-052b-9600000000-8b4b94cd7303c9b9a0ef
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0002-9000000000-c23b62afdf4dff8c43db
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0002-9000000000-e477cd71a628f6adaf46
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-052e-9000000000-61584ad991262d50a01b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0zfr-1980000000-84e04b032e6f422e5b6b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0aos-2900000000-e8d9297512335ce612fb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-052b-9800000000-7235208cf21d7ea1f7ad
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9300000000-4996f6630fe29fccd7d1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9100000000-a5e040b5d19e189571ba
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9000000000-d8853f62b77fc7f6ab01
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9000000000-a5bdbde532dc871c2dc3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-114j-9000000000-89e11e4ab1dbea690ecd
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-1000-9000000000-2968f2af0b540684c21f
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0090000000-b6ea3493555e798b637d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0aos-2910000000-c696b6aba5edd10fe848
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00kb-9700000000-6b130a82094066468edc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-9200000000-6f64d37f41bf3bddd538
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-9100000000-f23125855effae49cbd8
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0aor-0900000000-9d38315a88e4b11bc9e7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0pb9-2940000000-eb44b45cbe2d97c7791c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-9511000000-75fc9243ad1eb9c79cb4
1H NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as imidazoles. These are compounds containing an imidazole ring, which is an aromatic five-member ring with two nitrogen atoms at positions 1 and 3, and three carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Imidazoles
Alternative Parents
Heteroaromatic compounds / Guanidines / Sulfenyl compounds / Propargyl-type 1,3-dipolar organic compounds / Dialkylthioethers / Carboximidamides / Azacyclic compounds / Organopnictogen compounds / Imines / Hydrocarbon derivatives
Substituents
Imidazole / Heteroaromatic compound / Guanidine / Thioether / Carboximidamide / Sulfenyl compound / Propargyl-type 1,3-dipolar organic compound / Organic 1,3-dipolar compound / Dialkylthioether / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, guanidines, aliphatic sulfide, nitrile (CHEBI:3699)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Hernandez-Munoz R, Montiel-Ruiz C, Vazquez-Martinez O: Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats. Lab Invest. 2000 Aug;80(8):1161-9. [PubMed:10950107]
  3. Kuint J, Linder N, Reichman B: Hypoxemia associated with cimetidine therapy in a newborn infant. Am J Perinatol. 1996 Jul;13(5):301-3. [PubMed:8863950]
  4. Takahashi HK, Watanabe T, Yokoyama A, Iwagaki H, Yoshino T, Tanaka N, Nishibori M: Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes. Mol Pharmacol. 2006 Aug;70(2):450-3. Epub 2006 May 24. [PubMed:16723495]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [PubMed:10223772]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [PubMed:10385678]
  2. Furuta S, Kamada E, Suzuki T, Sugimoto T, Kawabata Y, Shinozaki Y, Sano H: Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole. Xenobiotica. 2001 Jan;31(1):1-10. doi: 10.1080/00498250110035615 . [PubMed:11334262]
  3. Satoh T, Fujita KI, Munakata H, Itoh S, Nakamura K, Kamataki T, Itoh S, Yoshizawa I: Studies on the interactions between drugs and estrogen: analytical method for prediction system of gynecomastia induced by drugs on the inhibitory metabolism of estradiol using Escherichia coli coexpressing human CYP3A4 with human NADPH-cytochrome P450 reductase. Anal Biochem. 2000 Nov 15;286(2):179-86. doi: 10.1006/abio.1999.4775. [PubMed:11067738]
  4. Park EJ, Cho HY, Lee YB: Effect of Cimetidine and Phenobarbital on metabolite kinetics of Omeprazole in rats. Arch Pharm Res. 2005 Oct;28(10):1196-202. [PubMed:16276979]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Details
3. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y: Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002 Aug;302(2):510-5. [PubMed:12130709]
  2. Satoh T, Fujita KI, Munakata H, Itoh S, Nakamura K, Kamataki T, Itoh S, Yoshizawa I: Studies on the interactions between drugs and estrogen: analytical method for prediction system of gynecomastia induced by drugs on the inhibitory metabolism of estradiol using Escherichia coli coexpressing human CYP3A4 with human NADPH-cytochrome P450 reductase. Anal Biochem. 2000 Nov 15;286(2):179-86. doi: 10.1006/abio.1999.4775. [PubMed:11067738]
  3. Park EJ, Cho HY, Lee YB: Effect of Cimetidine and Phenobarbital on metabolite kinetics of Omeprazole in rats. Arch Pharm Res. 2005 Oct;28(10):1196-202. [PubMed:16276979]
  4. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [PubMed:10223772]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  6. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [PubMed:10223772]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  3. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [PubMed:10223772]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  3. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [PubMed:10223772]
  2. Orishiki M, Matsuo Y, Nishioka M, Ichikawa Y: In vivo administration of H2 blockers, cimetidine and ranitidine, reduced the contents of the cytochrome P450IID (CYP2D) subfamily and their activities in rat liver microsomes. Int J Biochem. 1994 Jun;26(6):751-8. [PubMed:8063004]
  3. Ishii Y, Nakamura K, Tsutsumi K, Kotegawa T, Nakano S, Nakatsuka K: Drug interaction between cimetidine and timolol ophthalmic solution: effect on heart rate and intraocular pressure in healthy Japanese volunteers. J Clin Pharmacol. 2000 Feb;40(2):193-9. [PubMed:10664926]
  4. Furuta S, Kamada E, Suzuki T, Sugimoto T, Kawabata Y, Shinozaki Y, Sano H: Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole. Xenobiotica. 2001 Jan;31(1):1-10. doi: 10.1080/00498250110035615 . [PubMed:11334262]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
References
  1. Kenyon CJ, Fraser R, Birnie GG, Connell JM, Lever AF: Dose related in vitro effects of ranitidine and cimetidine on basal and ACTH-stimulated steroidogenesis. Gut. 1986 Oct;27(10):1143-6. [PubMed:3023203]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Furuta S, Kamada E, Suzuki T, Sugimoto T, Kawabata Y, Shinozaki Y, Sano H: Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole. Xenobiotica. 2001 Jan;31(1):1-10. doi: 10.1080/00498250110035615 . [PubMed:11334262]
  2. Cimetidine FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Rendic S: Drug interactions of H2-receptor antagonists involving cytochrome P450 (CYPs) enzymes: from the laboratory to the clinic. Croat Med J. 1999 Sep;40(3):357-67. [PubMed:10411963]
  3. Ohashi K, Sakamoto K, Sudo T, Tateishi T, Fujimura A, Shiga T, Ebihara A: Effects of diltiazem and cimetidine on theophylline oxidative metabolism. J Clin Pharmacol. 1993 Dec;33(12):1233-7. [PubMed:8126258]
  4. Knodell RG, Browne DG, Gwozdz GP, Brian WR, Guengerich FP: Differential inhibition of individual human liver cytochromes P-450 by cimetidine. Gastroenterology. 1991 Dec;101(6):1680-91. [PubMed:1955133]
  5. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Trimethylamine monooxygenase activity
Specific Function
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an impor...
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
Molecular Weight
60032.975 Da
References
  1. Cashman JR: Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism. Curr Drug Metab. 2000 Sep;1(2):181-91. [PubMed:11465082]
  2. Cashman JR, Park SB, Berkman CE, Cashman LE: Role of hepatic flavin-containing monooxygenase 3 in drug and chemical metabolism in adult humans. Chem Biol Interact. 1995 Apr 28;96(1):33-46. [PubMed:7720103]
  3. Hai X, Adams E, Hoogmartens J, Van Schepdael A: Enantioselective in-line and off-line CE methods for the kinetic study on cimetidine and its chiral metabolites with reference to flavin-containing monooxygenase genetic isoforms. Electrophoresis. 2009 Apr;30(7):1248-57. doi: 10.1002/elps.200800604. [PubMed:19283698]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Nadp binding
Specific Function
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name
FMO1
Uniprot ID
Q01740
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 1
Molecular Weight
60310.285 Da
References
  1. Hai X, Adams E, Hoogmartens J, Van Schepdael A: Enantioselective in-line and off-line CE methods for the kinetic study on cimetidine and its chiral metabolites with reference to flavin-containing monooxygenase genetic isoforms. Electrophoresis. 2009 Apr;30(7):1248-57. doi: 10.1002/elps.200800604. [PubMed:19283698]
  2. Cashman JR: Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism. Curr Drug Metab. 2000 Sep;1(2):181-91. [PubMed:11465082]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Romiti N, Tramonti G, Chieli E: Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line. Toxicol Appl Pharmacol. 2002 Sep 1;183(2):83-91. [PubMed:12387747]
  2. Lentz KA, Polli JW, Wring SA, Humphreys JE, Polli JE: Influence of passive permeability on apparent P-glycoprotein kinetics. Pharm Res. 2000 Dec;17(12):1456-60. [PubMed:11303953]
  3. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
  4. van der Sandt IC, Blom-Roosemalen MC, de Boer AG, Breimer DD: Specificity of doxorubicin versus rhodamine-123 in assessing P-glycoprotein functionality in the LLC-PK1, LLC-PK1:MDR1 and Caco-2 cell lines. Eur J Pharm Sci. 2000 Sep;11(3):207-14. [PubMed:11042226]
  5. Ito T, Yano I, Tanaka K, Inui KI: Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J Pharmacol Exp Ther. 1997 Aug;282(2):955-60. [PubMed:9262363]
  6. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [PubMed:11785684]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. 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. [PubMed:12089365]
  2. Motohashi H, Uwai Y, Hiramoto K, Okuda M, Inui K: Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol. 2004 Oct 25;503(1-3):25-30. [PubMed:15496291]
  3. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. [PubMed:12176030]
  4. 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. [PubMed:9808712]
  5. 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. [PubMed:10082798]
  6. Pan BF, Sweet DH, Pritchard JB, Chen R, Nelson JA: A transfected cell model for the renal toxin transporter, rOCT2. Toxicol Sci. 1999 Feb;47(2):181-6. [PubMed:10220855]
  7. Dudley AJ, Bleasby K, Brown CD: The organic cation transporter OCT2 mediates the uptake of beta-adrenoceptor antagonists across the apical membrane of renal LLC-PK(1) cell monolayers. Br J Pharmacol. 2000 Sep;131(1):71-9. [PubMed:10960071]
  8. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  9. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [PubMed:10385678]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. [PubMed:9187257]
  2. 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. [PubMed:9655880]
  3. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. [PubMed:12176030]
  4. Zhang L, Dresser MJ, Chun JK, Babbitt PC, Giacomini KM: Cloning and functional characterization of a rat renal organic cation transporter isoform (rOCT1A). J Biol Chem. 1997 Jun 27;272(26):16548-54. [PubMed:9195965]
  5. 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. [PubMed:9808712]
  6. 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. [PubMed:10082798]
  7. Jonker JW, Wagenaar E, Mol CA, Buitelaar M, Koepsell H, Smit JW, Schinkel AH: Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene. Mol Cell Biol. 2001 Aug;21(16):5471-7. [PubMed:11463829]
  8. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [PubMed:10385678]
  9. Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y: Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002 Aug;302(2):510-5. [PubMed:12130709]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Grundemann D, Schechinger B, Rappold GA, Schomig E: Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998 Sep;1(5):349-51. [PubMed:10196521]
  2. Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, Leibach FH, Ganapathy V: Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58. [PubMed:10966924]
  3. 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. [PubMed:9632645]
  4. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [PubMed:10385678]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific 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. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. 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. [PubMed:9618255]
  2. 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. [PubMed:10525100]
  3. 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. [PubMed:10454528]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [PubMed:11669456]
  2. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. [PubMed:14978359]
  3. Nagata Y, Kusuhara H, Endou H, Sugiyama Y: Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol. 2002 May;61(5):982-8. [PubMed:11961115]
  4. Burckhardt BC, Brai S, Wallis S, Krick W, Wolff NA, Burckhardt G: Transport of cimetidine by flounder and human renal organic anion transporter 1. Am J Physiol Renal Physiol. 2003 Mar;284(3):F503-9. Epub 2002 Nov 12. [PubMed:12429554]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [PubMed:11669456]
  2. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. [PubMed:14978359]
  3. Motohashi H, Uwai Y, Hiramoto K, Okuda M, Inui K: Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol. 2004 Oct 25;503(1-3):25-30. [PubMed:15496291]
  4. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. [PubMed:14762099]
  5. Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. [PubMed:15100168]
  6. Nagata Y, Kusuhara H, Endou H, Sugiyama Y: Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol. 2002 May;61(5):982-8. [PubMed:11961115]
  7. Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T: Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab. 2003 Apr;23(4):432-40. [PubMed:12679720]
  8. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [PubMed:11306713]
  9. Bakhiya A, Bahn A, Burckhardt G, Wolff N: Human organic anion transporter 3 (hOAT3) can operate as an exchanger and mediate secretory urate flux. Cell Physiol Biochem. 2003;13(5):249-56. [PubMed:14586168]
  10. Tahara H, Kusuhara H, Chida M, Fuse E, Sugiyama Y: Is the monkey an appropriate animal model to examine drug-drug interactions involving renal clearance? Effect of probenecid on the renal elimination of H2 receptor antagonists. J Pharmacol Exp Ther. 2006 Mar;316(3):1187-94. Epub 2005 Nov 16. [PubMed:16291876]
  11. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [PubMed:10224140]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Lai Y, Sampson KE, Balogh LM, Brayman TG, Cox SR, Adams WJ, Kumar V, Stevens JC: Preclinical and clinical evidence for the collaborative transport and renal secretion of an oxazolidinone antibiotic by organic anion transporter 3 (OAT3/SLC22A8) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1). J Pharmacol Exp Ther. 2010 Sep 1;334(3):936-44. doi: 10.1124/jpet.110.170753. Epub 2010 Jun 2. [PubMed:20519552]
  2. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [PubMed:17509534]
  3. Burt HJ, Neuhoff S, Almond L, Gaohua L, Harwood MD, Jamei M, Rostami-Hodjegan A, Tucker GT, Rowland-Yeo K: Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug-drug interactions. Eur J Pharm Sci. 2016 Jun 10;88:70-82. doi: 10.1016/j.ejps.2016.03.020. Epub 2016 Mar 25. [PubMed:27019345]
  4. Elsby R, Chidlaw S, Outteridge S, Pickering S, Radcliffe A, Sullivan R, Jones H, Butler P: Mechanistic in vitro studies confirm that inhibition of the renal apical efflux transporter multidrug and toxin extrusion (MATE) 1, and not altered absorption, underlies the increased metformin exposure observed in clinical interactions with cimetidine, trimethoprim or pyrimethamine. Pharmacol Res Perspect. 2017 Oct;5(5). doi: 10.1002/prp2.357. [PubMed:28971610]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. 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. [PubMed:10215651]
  2. 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. [PubMed:10825452]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. [PubMed:14978359]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
References
  1. Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T: Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14. [PubMed:12065749]
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [PubMed:10224140]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wilson A. (2016). New horizons in predictive drug metabolism and pharmacokinetics. The Royal Society of Chemistry. [ISBN:978-1-84973-828-6]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Data based on in vitro studies.
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [PubMed:17509534]
  2. Ito S, Kusuhara H, Yokochi M, Toyoshima J, Inoue K, Yuasa H, Sugiyama Y: Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney. J Pharmacol Exp Ther. 2012 Feb;340(2):393-403. doi: 10.1124/jpet.111.184986. Epub 2011 Nov 9. [PubMed:22072731]
  3. Dumitras S, Sechaud R, Drollmann A, Pal P, Vaidyanathan S, Camenisch G, Kaiser G: Effect of cimetidine, a model drug for inhibition of the organic cation transport (OCT2/MATE1) in the kidney, on the pharmacokinetics of glycopyrronium. Int J Clin Pharmacol Ther. 2013 Oct;51(10):771-9. doi: 10.5414/CP201946. [PubMed:24040847]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:43