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Record Information
Version2.0
Creation Date2009-07-21 20:27:02 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2810
Identification
Common NameCimetidine
ClassSmall Molecule
DescriptionA 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.
Compound Type
  • Adjuvant
  • Amide
  • Amine
  • Analgesic
  • Anti-Ulcer Agent
  • Drug
  • Enzyme Inhibitor
  • Ether
  • Histamine Antagonist
  • Histamine H2 Antagonist
  • Metabolite
  • Nitrile
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
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
Cimetidine Hcl
Cimetidinum
N''-cyano-N-methyl-n'-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]thio}ethyl)guanidine
N-Cyano-n'-methyl-n''-(2-([(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl)ethyl)guanidine
Tagamet
Tagamet HB
Tagamet hb 200
Tagamet HB200
Ulcedine
Ulcerfen
Ulcimet
Chemical FormulaC10H16N6S
Average Molecular Mass252.339 g/mol
Monoisotopic Mass252.116 g/mol
CAS Registry Number51481-61-9
IUPAC Name(Z)-N-cyano-N''-methyl-N'-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl)guanidine
Traditional Nametagamet HB
SMILESCN=C(NCCSCC1=C(C)N=CN1)NC#N
InChI IdentifierInChI=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)
InChI KeyInChIKey=AQIXAKUUQRKLND-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as imidazoles. Imidazoles 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassImidazoles
Direct ParentImidazoles
Alternative Parents
Substituents
  • Imidazole
  • Heteroaromatic compound
  • Guanidine
  • Thioether
  • Carboximidamide
  • Sulfenyl compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Dialkylthioether
  • Azacycle
  • Organic nitrogen compound
  • Organopnictogen compound
  • Imine
  • Organonitrogen compound
  • Organosulfur compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Cimetidine PathwayNot AvailableNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point142°C
Boiling PointNot Available
Solubility9380 mg/L (at 25°C)
LogP0.4
Predicted Properties
PropertyValueSource
Water Solubility0.82 g/LALOGPS
logP0.44ALOGPS
logP-0.11ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)13.38ChemAxon
pKa (Strongest Basic)6.91ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area88.89 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity70.32 m³·mol⁻¹ChemAxon
Polarizability27.47 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0005-9500000000-8ff5fa28797a788c95beJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0002-9511000000-75fc9243ad1eb9c79cb4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0a4j-5900000000-122f9dbdf583bbe3dee8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0002-9300000000-39ee157d9e264867cfa4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0002-9000000000-6e876a668444c8277412JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0002-9000000000-85640be9b2799889fd02JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0002-9000000000-9b8d3eafde213bee6396JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0a4j-9000000000-b47e11697992a843f5e4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0a4i-9000000000-75ebe86c90f5ed341c57JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0aor-9000000000-d7302885bef7454b4db2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014i-9000000000-b2f3ab1b5ae1e2f8f8bbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-0930000000-dbae8348b5c999cc664dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-052b-9600000000-8b4b94cd7303c9b9a0efJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0002-9000000000-c23b62afdf4dff8c43dbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0002-9000000000-e477cd71a628f6adaf46JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-052e-9000000000-61584ad991262d50a01bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0zfr-1980000000-84e04b032e6f422e5b6bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0aos-2900000000-e8d9297512335ce612fbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-052b-9800000000-7235208cf21d7ea1f7adJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-9300000000-4996f6630fe29fccd7d1JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0ufs-7790000000-535b3b79ad51bbf5a724JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-056s-5910000000-059a8f3e3eb08432dd72JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-9100000000-ceadcc70f9905df3cd1bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0ufs-7960000000-d054508682ae0a8a700dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0adm-5910000000-05af2f300dae46b29b5fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-43451f5e853f064cd924JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-002b-9510000000-36ce01132725fd5bf5d8JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureOral, rapid 60-70%
Mechanism of ToxicityCimetidine 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.
MetabolismHepatic Route of Elimination: The principal route of excretion of cimetidine is the urine. Half Life: 2 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (4)
Uses/SourcesFor the treatment and the management of acid-reflux disorders (GERD), peptic ulcer disease, heartburn, and acid indigestion.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include nausea, vomiting, diarrhea, increased saliva production, difficulty breathing, and a fast heartbeat.
TreatmentThe usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring and supportive therapy should be employed. (3)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00501
HMDB IDHMDB14644
PubChem Compound ID2756
ChEMBL IDCHEMBL30
ChemSpider ID2654
KEGG IDC06952
UniProt IDNot Available
OMIM ID
ChEBI ID3699
BioCyc IDNot Available
CTD IDNot Available
Stitch IDCimetidine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCimetidine
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.

MSDSLink
General References
  1. Michnovicz JJ, Galbraith RA: Cimetidine inhibits catechol estrogen metabolism in women. Metabolism. 1991 Feb;40(2):170-4. [1988774 ]
  2. Drugs.com [Link]
  3. RxList: The Internet Drug Index (2009). [Link]
  4. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

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 differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity).
Gene Name:
HRH2
Uniprot ID:
P25021
Molecular Weight:
40097.65 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.14 uMNot AvailableBindingDB 50403559
IC500.14 uMNot AvailableBindingDB 50403559
IC500.27 uMNot AvailableBindingDB 50403559
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [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. [10950107 ]
  3. 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. [16723495 ]
  4. Kuint J, Linder N, Reichman B: Hypoxemia associated with cimetidine therapy in a newborn infant. Am J Perinatol. 1996 Jul;13(5):301-3. [8863950 ]
  5. Cappelli A, Manini M, Valenti S, Castriconi F, Giuliani G, Anzini M, Brogi S, Butini S, Gemma S, Campiani G, Giorgi G, Mennuni L, Lanza M, Giordani A, Caselli G, Letari O, Makovec F: Synthesis and structure-activity relationship studies in serotonin 5-HT(1A) receptor agonists based on fused pyrrolidone scaffolds. Eur J Med Chem. 2013 May;63:85-94. doi: 10.1016/j.ejmech.2013.01.044. Epub 2013 Feb 8. [23466604 ]
  6. Veinberg G, Vorona M, Zvejniece L, Vilskersts R, Vavers E, Liepinsh E, Kazoka H, Belyakov S, Mishnev A, Kuznecovs J, Vikainis S, Orlova N, Lebedev A, Ponomaryov Y, Dambrova M: Synthesis and biological evaluation of 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide stereoisomers as novel positive allosteric modulators of sigma-1 receptor. Bioorg Med Chem. 2013 May 15;21(10):2764-71. doi: 10.1016/j.bmc.2013.03.016. Epub 2013 Mar 24. [23582449 ]
  7. Nakai T, Kitamura N, Hashimoto T, Kajimoto Y, Nishino N, Mita T, Tanaka C: Decreased histamine H1 receptors in the frontal cortex of brains from patients with chronic schizophrenia. Biol Psychiatry. 1991 Aug 15;30(4):349-56. [1912125 ]
  8. Hosking MP, Lennon RL, Gronert GA: Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high-dose atracurium for rapid sequence endotracheal intubation. Anesth Analg. 1988 Nov;67(11):1089-92. [2461127 ]
  9. Alewijnse AE, Smit MJ, Hoffmann M, Verzijl D, Timmerman H, Leurs R: Constitutive activity and structural instability of the wild-type human H2 receptor. J Neurochem. 1998 Aug;71(2):799-807. [9681472 ]
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 molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. 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. [12429554 ]
  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. [14978359 ]
  3. Hashimoto T, Narikawa S, Huang XL, Minematsu T, Usui T, Kamimura H, Endou H: Characterization of the renal tubular transport of zonampanel, a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, by human organic anion transporters. Drug Metab Dispos. 2004 Oct;32(10):1096-102. [15377641 ]
  4. 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. [15496291 ]
  5. Ueo H, Motohashi H, Katsura T, Inui K: Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1. Biochem Pharmacol. 2005 Oct 1;70(7):1104-13. [16098483 ]
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory77 uMNot AvailableBindingDB 50403559
References
  1. Fontana E, Dansette PM, Poli SM: Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab. 2005 Oct;6(5):413-54. [16248836 ]
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 sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.2 uMNot AvailableBindingDB 50403559
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
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
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>50 uMNot AvailableBindingDB 50403559
References
  1. 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. [12699389 ]