CIMETIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H16N6S
Molecular Weight	252.339
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(NCCSCC1=C(C)NC=N1)=NC#N

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 46 Target ID: CHEMBL1941 Sources: http://www.drugbank.ca/drugs/DB00501	Antagonist 2849		70.0 nM [Ki]
Multidrug and toxin extrusion protein 1 3 Target ID: CHEMBL1743126 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23241029	Inhibitor 8504		1.2 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Stomach Ulcer 2 Sources: https://www.drugs.com/cdi/tagamet.html	Primary		Approved 8583	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 1995
Gastroesophageal reflux disease 68 Sources: https://www.drugs.com/cdi/tagamet.html	Primary		Approved 8583	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 1995

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) Health Status: unhealthy Age Group: 50 years (range: 22-85 years) 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 Health Status: unhealthy Age Group: adult 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 Health Status: unhealthy Age Group: adult Sex: M 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) Health Status: unhealthy Age Group: 50 years (range: 22-85 years) 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) Health Status: unhealthy Age Group: 50 years (range: 22-85 years) 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) Health Status: unhealthy Age Group: 50 years (range: 22-85 years) 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) Health Status: unhealthy Age Group: 50 years (range: 22-85 years) 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) Health Status: unhealthy Age Group: 50 years (range: 22-85 years) Sources: https://pubmed.ncbi.nlm.nih.gov/3520794

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP3A4/5 296 CYP2C19 2057 MATE1 415 OCT2 779 OAT3 747 MATE2 267 OCT1 620	OAT3 391 MATE1 182 MATE2 98

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 110 uM]
OCT1 656	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 149 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/ Page: 3.0	yes [IC50 200 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/ Page: 4.0	yes [IC50 210 uM]
CYP3A4/5 357	inhibitor 4027 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 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17314201/	yes [IC50 79 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11334262/ Page: 3.0	yes [Inhibition 10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11334262/ Page: 5.0	yes [Ki 157.8 uM]
MATE2 267	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22072731/	yes [Ki 2.1 uM]
MATE1 416	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22072731/	yes [Ki 3.8 uM]

Drug as victim

Target	Modality	Activity
MATE1 182	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MATE2 98	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
OAT3 391	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16006492/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 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
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
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

PubMed

Title	Date	PubMed
Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity.	1991	1676005
Decreased histamine H1 receptors in the frontal cortex of brains from patients with chronic schizophrenia.	1991 Aug 15	1912125
Cimetidine inhibits catechol estrogen metabolism in women.	1991 Feb	1988774
[A case of acute interstitial nephritis and nonoliguria acute renal failure induced by cimetidine].	1992 Nov	1294777
Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain.	1999 May 7	10224140
Effects of three H2-receptor antagonists (cimetidine, famotidine, ranitidine) on serum gastrin level.	2002	12503773
Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum.	2002	12442916
Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis.	2002 Jul	12065299
Weekly 1-h paclitaxel infusion in patients with recurrent endometrial cancer: a preliminary study.	2003 Feb	12601542
Cimetidine reduces impairment of cellular immunity after transcatheter arterial embolization in patients with hepatocellular carcinoma.	2003 Mar-Apr	12749247
Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A).	2004 Oct 25	15496291
Cimetidine-induced tubulointerstitial nephritis with both MPO-ANCA and PR3-ANCA.	2005 Dec	16362162
Sex-dependent expression and activity of the ATP-binding cassette transporter breast cancer resistance protein (BCRP/ABCG2) in liver.	2005 May	15722455
Alteration of intracellular histamine H2 receptor cycling precedes antagonist-induced upregulation.	2005 Nov	15961859
A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters.	2005 Oct	16006492
Effect of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine as evaluated by step-through avoidance response in rats.	2006 Apr 15	16488453
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
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.	2006 Mar	16291876
Involvement of human multidrug and toxin extrusion 1 in the drug interaction between cimetidine and metformin in renal epithelial cells.	2009 Apr	19164462
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
Inhibitory effects of the antiepileptic drug ethosuximide on G protein-activated inwardly rectifying K+ channels.	2009 Feb	18977371
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
The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity.	2009 Mar	19144690
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

ACILOC

Preferred Name

English

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

DYSPAMET

Brand Name

English

GASTROMET

Common Name

English

Cimetidine [WHO-DD]

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

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