CIMETIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H16N6S
Molecular Weight	252.3407
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1c(CSCCNC(=NC)NC#N)[nH]cn1

InChI

InChIKey=AQIXAKUUQRKLND-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00501
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/cdi/cimetidine.html

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. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H2 receptor 43 Target ID: CHEMBL1941 Sources: http://www.drugbank.ca/drugs/DB00501	Antagonist 2577		70.0 nM [Ki]
Multidrug and toxin extrusion protein 1 3 Target ID: CHEMBL1743126 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23241029	Inhibitor 7701		1.2 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Stomach Ulcer 2 Sources: https://www.drugs.com/cdi/tagamet.html	Primary		Approved 7997	TAGAMET Approved Use Treating and preventing ulcers of the stomach and small intestine, and treating gastroesophageal reflux disease (GERD). It may be used for treating esophagitis (inflammation of the esophagus) caused by acid reflux and certain conditions that cause increased acid secretion (eg, Zollinger-Ellison syndrome). Launch Date 8.0343361E11
Gastroesophageal reflux disease 56 Sources: https://www.drugs.com/cdi/tagamet.html	Primary		Approved 7997	TAGAMET Approved Use Treating and preventing ulcers of the stomach and small intestine, and treating gastroesophageal reflux disease (GERD). It may be used for treating esophagitis (inflammation of the esophagus) caused by acid reflux and certain conditions that cause increased acid secretion (eg, Zollinger-Ellison syndrome). Launch Date 8.0343361E11

C_max

Value	Dose	Co-administered	Analyte	Population
1.056 μg/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75285_Cimetidine.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		CIMETIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
4.22 μg × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75285_Cimetidine.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		CIMETIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.4 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75285_Cimetidine.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		CIMETIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3520794	unhealthy, 50 years (range: 22-85 years) n = 17 Health Status: unhealthy Age Group: 50 years (range: 22-85 years) Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/3520794	Other AEs: Headache, Abdominal pain... Other AEs: Headache (2 patients) Abdominal pain (2 patients) Nausea (2 patients) Anorexia (2 patients) Vomiting (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/3520794
20 g single, oral Overdose Dose: 20 g Route: oral Route: single Dose: 20 g Sources: https://pubmed.ncbi.nlm.nih.gov/92705	unhealthy, adult n = 3 Health Status: unhealthy Age Group: adult Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/92705	Sources: https://pubmed.ncbi.nlm.nih.gov/92705
3 g 4 times / day multiple, oral Overdose Dose: 3 g, 4 times / day Route: oral Route: multiple Dose: 3 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/74598	unhealthy, adult n = 1 Health Status: unhealthy Condition: duodenal ulcer Age Group: adult Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/74598	Sources: https://pubmed.ncbi.nlm.nih.gov/74598
300 mg 4 times / day multiple, respiratory Recommended Dose: 300 mg, 4 times / day Route: respiratory Route: multiple Dose: 300 mg, 4 times / day Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aa4ee5b-b5be-4a98-5b8c-6f75e2b59e51	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aa4ee5b-b5be-4a98-5b8c-6f75e2b59e51	Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aa4ee5b-b5be-4a98-5b8c-6f75e2b59e51

AEs

AE	Significance	Dose	Population
Abdominal pain	2 patients	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3520794	unhealthy, 50 years (range: 22-85 years) n = 17 Health Status: unhealthy Age Group: 50 years (range: 22-85 years) Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/3520794
Anorexia	2 patients	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3520794	unhealthy, 50 years (range: 22-85 years) n = 17 Health Status: unhealthy Age Group: 50 years (range: 22-85 years) Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/3520794
Headache	2 patients	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3520794	unhealthy, 50 years (range: 22-85 years) n = 17 Health Status: unhealthy Age Group: 50 years (range: 22-85 years) Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/3520794
Nausea	2 patients	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3520794	unhealthy, 50 years (range: 22-85 years) n = 17 Health Status: unhealthy Age Group: 50 years (range: 22-85 years) Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/3520794
Vomiting	2 patients	1200 mg 1 times / day multiple, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3520794	unhealthy, 50 years (range: 22-85 years) n = 17 Health Status: unhealthy Age Group: 50 years (range: 22-85 years) Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/3520794

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1318	inhibitor 1421	inhibitor 1360

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1268 CYP3A4/5 225 CYP2C19 1215 MATE1 290 OCT2 582 OAT3 570 MATE2 258 OCT1 473	OAT3 299 MATE1 123 MATE2 91

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OCT2 583	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 110 uM]
OCT1 488	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 149 uM]
CYP1A2 1406	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/ Page: 3.0	yes [IC50 200 uM]
CYP2D6 1455	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/ Page: 4.0	yes [IC50 210 uM]
CYP3A4/5 277	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/ Page: 4.0	yes [IC50 480 uM]	yes (co-administration study) Comment: Coadministration with midazolam: [AUC(0-12)] and AUC(0-∞) values for midazolam were 507.0 ± 265.1 (40%) and 786.1 ± 365.2 (50%) nmol/mL · h, respectively; Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/ Page: 4.0
OAT3 572	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/17314201/	yes [IC50 79 uM]
CYP2C9 1362	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/11334262/ Page: 3.0	yes [Inhibition 10 uM]
CYP2C19 1277	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/11334262/ Page: 5.0	yes [Ki 157.8 uM]
MATE2 258	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/22072731/	yes [Ki 2.1 uM]
MATE1 291	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/22072731/	yes [Ki 3.8 uM]

Drug as victim

Target	Modality	Activity
MATE1 123	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MATE2 91	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
OAT3 299	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/16006492/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1392	inhibitor 1374 Sources: https://pubmed.ncbi.nlm.nih.gov/16278312/ Page: 3.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3699	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3699
ChemicalBook	CB31086794	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB31086794
ChemicalBook	CB4229414	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4229414
MolPort	MolPort-001-838-193	https://www.molport.com/shop/molecule-link/MolPort-001-838-193
MolPort	MolPort-003-895-998	https://www.molport.com/shop/molecule-link/MolPort-003-895-998
MolPort	MolPort-016-638-396	https://www.molport.com/shop/molecule-link/MolPort-016-638-396
MolPort	MolPort-020-313-426	https://www.molport.com/shop/molecule-link/MolPort-020-313-426
MolPort	MolPort-042-675-761	https://www.molport.com/shop/molecule-link/MolPort-042-675-761
Selleck Chemicals	Cimetidine(Tagamet)	http://www.selleckchem.com/products/Cimetidine(Tagamet).html
ZINC	ZINC000018115268	http://zinc15.docking.org/substances/ZINC000018115268
eMolecules	1107425	https://www.emolecules.com/cgi-bin/more?vid=1107425
eMolecules	19230646	https://www.emolecules.com/cgi-bin/more?vid=19230646
eMolecules	26714830	https://www.emolecules.com/cgi-bin/more?vid=26714830
eMolecules	6208997	https://www.emolecules.com/cgi-bin/more?vid=6208997
eMolecules	901649	https://www.emolecules.com/cgi-bin/more?vid=901649

PubMed

Title	Date	PubMed
[Cimetidine-induced aplastic anemia complicated with nonbacterial thrombotic endocarditis and cerebral infarction].	1990 Dec	2079735
[Confusion induced by the combination cimetidine-benzodiazepine; apropos of a case report].	1990 Jan	1968690
Hemodynamic effects of H2-receptor antagonists.	1990 Nov	1980182
Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity.	1991	1676005
Cimetidine inhibits catechol estrogen metabolism in women.	1991 Feb	1988774
[Cimetidine hepatitis].	1992 Dec 15	1289197
Cimetidine-dobutamine interaction?	1992 Nov	1466438
[A case of acute interstitial nephritis and nonoliguria acute renal failure induced by cimetidine].	1992 Nov	1294777
Polyuria and weight-loss associated with cimetidine.	1992 Sep	1480549
Activity of cathepsin B, D and L in rat cerebrum after cimetidine and famotidine administration.	2003	12903910
Role of cytochrome P450 2B1 in puromycin aminonucleoside-induced cytotoxicity to glomerular epithelial cells.	2003	12806184
Histamine inhibits atrial myocytic ANP release via H2 receptor-cAMP-protein kinase signaling.	2003 Aug	12714356
Radioprotective properties of histamine H2 receptor antagonists: present and future prospects.	2003 Jun	13678344
Cimetidine reduces impairment of cellular immunity after transcatheter arterial embolization in patients with hepatocellular carcinoma.	2003 Mar-Apr	12749247
Bioequivalence and other unresolved issues in generic drug substitution.	2003 Nov	14693311
[Roles of histamine receptors in pain perception: a study using receptors gene knockout mice].	2003 Nov	14569158
Regulation of cytokine production in carcinoembryonic antigen stimulated Kupffer cells by beta-2 adrenergic receptors: implications for hepatic metastasis.	2004 Jun 25	15159029
Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3.	2004 May	15100168
Relative contribution of OAT and OCT transporters to organic electrolyte transport in rabbit proximal tubule.	2004 Nov	15251863
Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A).	2004 Oct 25	15496291
Carrier-mediated uptake of H2-receptor antagonists by the rat choroid plexus: involvement of rat organic anion transporter 3.	2004 Sep	15319347
Comparison of information on the pharmacokinetic interactions of Ca antagonists in the package inserts from three countries (Japan, USA and UK).	2005 Aug	16041596
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A.	2005 Feb 27	15799453
Human breast cancer resistance protein: interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine.	2005 Jan	15365089
Interaction of organic cations with a newly identified plasma membrane monoamine transporter.	2005 Nov	16099839
Alteration of intracellular histamine H2 receptor cycling precedes antagonist-induced upregulation.	2005 Nov	15961859
Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes.	2006 Aug	16723495
In vitro availability of metformin in presence of h(2) receptor antagonists.	2006 Jan	16632449
Putting theory into practice: James Black, receptor theory and the development of the beta-blockers at ICI, 1958-1978.	2006 Jan	16502872
Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney.	2006 Nov	16928787
Effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and surface expression of endothelial adhesion molecules induced by high glucose levels.	2007 Jan-Feb	17189874
Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters.	2007 Jul 15	17509534
Cimetidine inhibits epidermal growth factor-induced cell signaling.	2007 Mar	17295779
Effect of sodium ozagrel on the activity of rat CYP2D6.	2007 Nov 14	17651725
Caki-1 cells as a model system for the interaction of renally secreted drugs with OCT3.	2008	18253050
Morphological evidences indicate that the interference of cimetidine on the peritubular components is responsible for detachment and apoptosis of Sertoli cells.	2008 May 9	18471284
Ameliorative effects of histamine on spatial memory deficits induced by scopolamine infusion into bilateral dorsal or ventral hippocampus as evaluated by the radial arm maze task.	2009 Aug	19215234
Androgen action via testicular peritubular myoid cells is essential for male fertility.	2009 Dec	19692648
Ocular surface tumors.	2009 Jan	21234217
Gastroprotective activity of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora Krause (Rutaceae).	2009 Jul 15	19497430
Pharmacokinetics of cimetidine in dogs after oral administration of cimetidine tablets.	2009 Jun	19646084
Ligand diversity of human and chimpanzee CYP3A4: activation of human CYP3A4 by lithocholic acid results from positive selection.	2009 Jun	19299527
Enhanced ERbeta immunoexpression and apoptosis in the germ cells of cimetidine-treated rats.	2009 Nov 18	19922658
Antiulcer and anticonvulsant activity of Croton zambesicus.	2009 Oct	19783516
Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney.	2010	20332632
Size-dependent effects of nanoparticles on the activity of cytochrome P450 isoenzymes.	2010 Feb 1	19909766
Contribution of mast cells to the oedema induced by Bothrops moojeni snake venom and a pharmacological assessment of the inflammatory mediators involved.	2010 Feb-Mar	19703484
Drug interaction and pharmacist.	2010 Jul	21042495
Two cases of h(2)-receptor antagonist hypersensitivity and cross-reactivity.	2011 Apr	21461253
Involvement of histaminergic receptor mechanisms in the stimulation of NT-3 synthesis in astrocytes.	2011 Jun	21276809

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Duodenal Ulcer Parenteral: 300 mg IV or IM every 6 to 8 hours. Alternatively, a continuous IV infusion may be administered at a rate of 37.5 to 50 mg/hour, or up to a maximum rate of 100 mg/hour (2.4 g/day). Oral: 800 mg to 1600 mg once a day at bedtime. Alternatively, dosage regimens of 300 mg four times per day, with meals and at bedtime, or 400 mg twice daily, in the morning and at bedtime, have shown to be effective.

Route of Administration: Other

In Vitro Use Guide

Cimetidine (10(-7)M) inhibited IL-10 production and restored IL-12 secretion in LPS-treated murine DCs.

Name

Type

Language

CIMETIDINE

Official Name

English

CIMETIDINE [MI]

Common Name

English

2-CYANO-1-METHYL-3-(2-(((5-METHYLIMIDAZOL-4-YL)METHYL)THIO)ETHYL)-GUANIDINE

Systematic Name

English

CIMETIDINE [JAN]

Common Name

English

CIMETIDINE [USAN]

Common Name

English

BRUMETIDINA

Brand Name

English

CIMETIDINE [IARC]

Common Name

English

TAGAMET

Brand Name

English

CIMAL

Brand Name

English

CIMETIDINE [MART.]

Common Name

English

ACINIL

Brand Name

English

STOMEDINE

Brand Name

English

CIMETIDINE [WHO-DD]

Common Name

English

DYSPAMET

Brand Name

English

GASTROMET

Common Name

English

CIMETIDINE [INN]

Common Name

English

CIMETIDINUM [WHO-IP LATIN]

Common Name

English

ULCEDIN

Brand Name

English

ULCOMEDINA

Common Name

English

CIMETIDINE [WHO-IP]

Common Name

English

GUANIDINE, N''-CYANO-N-METHYL-N'-(2-(((5-METHYL-1H-IMIDAZOL-4-YL)METHYL)THIO)ETHYL)-

Systematic Name

English

CIMETIDINE [HSDB]

Common Name

English

SKF-92334

Code

English

CIMETIDINE [USP-RS]

Common Name

English

ULCIMET

Brand Name

English

CIMETIDINE [USP MONOGRAPH]

Common Name

English

ACILOC

Brand Name

English

CIMETIDINE [VANDF]

Common Name

English

CIMETIDINE [EP MONOGRAPH]

Common Name

English

CIMETIDINE [ORANGE BOOK]

Common Name

English

NSC-335308

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C29702