RANITIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H22N4O3S
Molecular Weight	314.404
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(NCCSCC1=CC=C(CN(C)C)O1)=C[N+]([O-])=O

InChI

InChIKey=VMXUWOKSQNHOCA-LCYFTJDESA-N

InChI=1S/C13H22N4O3S/c1-14-13(9-17(18)19)15-6-7-21-10-12-5-4-11(20-12)8-16(2)3/h4-5,9,14-15H,6-8,10H2,1-3H3/b13-9-

HIDE SMILES / InChI

Molecular Formula	C13H22N4O3S
Molecular Weight	314.404
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2667937,6309467

Ranitidine, a histamine H2-receptor antagonist, is now well established as a potent inhibitor of gastric acid secretion effective in the treatment and prophylaxis of gastrointestinal lesions aggravated by gastric acid secretion.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histamine H2 receptor 45 Target ID: P25102 Gene ID: 25461.0 Gene Symbol: Hrh2 Target Organism: Rattus norvegicus (Rat) Sources: http://www.pnas.org/content/93/13/6802.full.pdf	Antagonist 2737	0.14 µM [Ki]
Histamine H2 receptor 45 Target ID: P47747 Gene ID: NA Gene Symbol: HRH2 Target Organism: Cavia porcellus (Guinea pig) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9205741	Antagonist 2737	0.19 µM [Ki]
Histamine H2 receptor 45 Target ID: P25021 Gene ID: 3274.0 Gene Symbol: HRH2 Target Organism: Homo sapiens (Human) Sources: http://ca.gsk.com/media/592906/zantac.pdf	Antagonist 2737

Conditions

Condition	Modality	Highest Phase	Product
Duodenal ulcer 41 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8307	ZANTAC 150 Approved Use ZANTAC® (ranitidine hydrochloride) Tablets and Injection are indicated for the treatment of duodenal ulcer, benign gastric ulcer, reflux esophagitis, post-operative peptic ulcer, Zollinger-Ellison Syndrome, and other conditions where reduction of gastric secretion and acid output is desirable. These include the following: • the treatment of nonsteroidal anti-inflammatory drug (NSAID)- induced lesions, both ulcers and erosions, and their gastrointestinal (GI) symptoms and the prevention of their recurrence; • the prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients; • the prophylaxis of recurrent hemorrhage from bleeding ulcers; • the prevention of Acid Aspiration Syndrome from general anaesthesia in patients considered to be at risk for this, including obstetrical patients in labour, and obese patients. In addition, ZANTAC® is indicated for the prophylaxis and maintenance treatment of duodenal or benign gastric ulcer in patients with a history of recurrent ulceration. Launch Date 4.23964803E11
Gastric ulcer 61 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8307	ZANTAC 150 Approved Use ZANTAC® (ranitidine hydrochloride) Tablets and Injection are indicated for the treatment of duodenal ulcer, benign gastric ulcer, reflux esophagitis, post-operative peptic ulcer, Zollinger-Ellison Syndrome, and other conditions where reduction of gastric secretion and acid output is desirable. These include the following: • the treatment of nonsteroidal anti-inflammatory drug (NSAID)- induced lesions, both ulcers and erosions, and their gastrointestinal (GI) symptoms and the prevention of their recurrence; • the prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients; • the prophylaxis of recurrent hemorrhage from bleeding ulcers; • the prevention of Acid Aspiration Syndrome from general anaesthesia in patients considered to be at risk for this, including obstetrical patients in labour, and obese patients. In addition, ZANTAC® is indicated for the prophylaxis and maintenance treatment of duodenal or benign gastric ulcer in patients with a history of recurrent ulceration. Launch Date 4.23964803E11
Gastroesophageal reflux disease 61 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8307	ZANTAC 150 Approved Use ZANTAC® (ranitidine hydrochloride) Tablets and Injection are indicated for the treatment of duodenal ulcer, benign gastric ulcer, reflux esophagitis, post-operative peptic ulcer, Zollinger-Ellison Syndrome, and other conditions where reduction of gastric secretion and acid output is desirable. These include the following: • the treatment of nonsteroidal anti-inflammatory drug (NSAID)- induced lesions, both ulcers and erosions, and their gastrointestinal (GI) symptoms and the prevention of their recurrence; • the prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients; • the prophylaxis of recurrent hemorrhage from bleeding ulcers; • the prevention of Acid Aspiration Syndrome from general anaesthesia in patients considered to be at risk for this, including obstetrical patients in labour, and obese patients. In addition, ZANTAC® is indicated for the prophylaxis and maintenance treatment of duodenal or benign gastric ulcer in patients with a history of recurrent ulceration. Launch Date 4.23964803E11
Zollinger-Ellison syndrome 16 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018703s065,019675s031,020251s016lbl.pdf	Primary	Approved 8307	ZANTAC 150 Approved Use ZANTAC® (ranitidine hydrochloride) Tablets and Injection are indicated for the treatment of duodenal ulcer, benign gastric ulcer, reflux esophagitis, post-operative peptic ulcer, Zollinger-Ellison Syndrome, and other conditions where reduction of gastric secretion and acid output is desirable. These include the following: • the treatment of nonsteroidal anti-inflammatory drug (NSAID)- induced lesions, both ulcers and erosions, and their gastrointestinal (GI) symptoms and the prevention of their recurrence; • the prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients; • the prophylaxis of recurrent hemorrhage from bleeding ulcers; • the prevention of Acid Aspiration Syndrome from general anaesthesia in patients considered to be at risk for this, including obstetrical patients in labour, and obese patients. In addition, ZANTAC® is indicated for the prophylaxis and maintenance treatment of duodenal or benign gastric ulcer in patients with a history of recurrent ulceration. Launch Date 4.23964803E11

C_max

Value	Dose	Co-administered	Analyte	Population
440 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018703s068,019675s035,020251s019lbl.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
948.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6094785/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.69 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6094785/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018703s068,019675s035,020251s019lbl.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
85% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018703s068,019675s035,020251s019lbl.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg single, oral Highest studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6329583/	healthy, adult n = 136 Health Status: healthy Age Group: adult Sex: M+F Population Size: 136 Sources: https://pubmed.ncbi.nlm.nih.gov/6329583/	Sources: https://pubmed.ncbi.nlm.nih.gov/6329583/
1500 mg single, oral Overdose Dose: 1500 mg Route: oral Route: single Dose: 1500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28425352/	unknown, children n = 517 Health Status: unknown Age Group: children Sex: unknown Population Size: 517 Sources: https://pubmed.ncbi.nlm.nih.gov/28425352/	Sources: https://pubmed.ncbi.nlm.nih.gov/28425352/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1532 substrate 1670		inhibitor 1789 substrate 1168

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 498 OCT2 630 OCT3 143 MATE1 302 MATE2 259 CYP3A 208 CYP1A2 1463	OCT1 317 OCT2 336 OCT3 76 P-gp 1491 FMO3 65 FMO1 16 CYP1A2 1013 CYP2A6 510 CYP2C19 955 CYP2E1 633

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/	no
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/	no
CYP3A 291	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/	no	no (co-administration study) Comment: Ranitidine has no effect on midazolam exposure Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/
OCT3 143	inhibitor 3185 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	weak [IC50 290 uM]
CYP3A4 1857	inhibitor 3185 Sources: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers	weak
OCT2 631	inhibitor 3185 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes [IC50 114 uM]
MATE1 304	inhibitor 3185 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20053795	yes [IC50 18.9 uM]
OCT1 513	inhibitor 3185 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes [IC50 28 uM]
MATE2 259	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 25 uM]

Drug as victim

Target	Modality	Activity
FMO3 65	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	major
FMO1 16	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	minor
OCT2 336	substrate 3264 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	minor
CYP2A6 510	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
CYP2E1 633	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
OCT3 76	substrate 3264 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	no
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
CYP2D6 1168	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
OCT1 317	substrate 3264 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes
P-gp 1491	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/9862768/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8776	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8776
ChemicalBook	CB5480252	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5480252
MolPort	MolPort-003-666-370	https://www.molport.com/shop/molecule-link/MolPort-003-666-370
ZINC	ZINC000001530728	http://zinc15.docking.org/substances/ZINC000001530728

PubMed

Title	Date	PubMed
Comparison of ranitidine and high-dose antacid in the treatment of prepyloric or duodenal ulcer. A double-blind controlled trial.	1985 Jan	3887547
Bradycardia and neurologic disorders associated with ranitidine in a child.	1985 May	3984961
Mental confusion as a side effect of ranitidine.	1986 Feb	3946668
Depression associated with ranitidine.	1986 Jul	3717435
Myofascial headache. Exacerbation of symptoms due to diflunisal and ranitidine therapy. A case report.	1987 Aug	3308026
Histamine and hepatic glutathione in the mouse.	1987 May 25	2884542
Mania associated with intravenous ranitidine therapy.	1987 Nov	3500517
Fatal renal and hepatic toxicity after treatment with diltiazem.	1987 Nov 14	3120959
Famotidine-associated mental confusion in elderly patients.	1988 Dec	3243179
Reversible chorea due to ranitidine and cimetidine.	1988 Jul 16	2899203
Ranitidine and bradycardia.	1988 Mar	3341694
Cardiac arrest associated with ranitidine.	1989 Aug 19	2507055
Famotidine and ranitidine, but not cimetidine, cause severe, disabling headache.	1989 Feb	2563629
Ranitidine-induced chest pain.	1989 Mar	2718500
Histamine release in the isolated vascularly perfused stomach of the rat: regulation by autoreceptors.	1989 Mar	2470453
Effect of ranitidine on acetaminophen-induced hepatotoxicity in dogs.	1990 Mar	2307085
Effects of histamine H2-receptor blockade on the cardiovascular reflex response to lower-body negative pressure in man.	1990 May	1972605
Seizures during concomitant treatment with theophylline and ranitidine: a case report.	1990 Oct-Dec	2093363
Ranitidine-associated delirium.	1990 Winter	2300661
Ranitidine and depression.	1991 Sep	1958166
Ranitidine pharmacokinetics and adverse central nervous system reactions.	1992 Nov	1444693
Effects of three H2-receptor antagonists (cimetidine, famotidine, ranitidine) on serum gastrin level.	2002	12503773
Effects of H(2)-receptor antagonists on dapsone-induced methaemoglobinaemia in rats.	2002 Apr	12030789
Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials.	2002 Jul 15	12119060
Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [(3) H]tiotidine binding.	2002 Jun	12065605
Drug points: Severe myalgia from an interaction between treatments with pantoprazole and methotrexate.	2002 Jun 22	12077038
Effects of histamine H(2)-receptor antagonists on human plasma levels of calcitonin gene-related peptide, substance P and vasoactive intestinal peptide.	2002 Nov	12495560
Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells.	2003	14671421
Radioprotective properties of histamine H2 receptor antagonists: present and future prospects.	2003 Jun	13678344
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.	2004 Nov	15286053
Carrier-mediated uptake of H2-receptor antagonists by the rat choroid plexus: involvement of rat organic anion transporter 3.	2004 Sep	15319347
Lethal cardiomyopathy in epidermolysis bullosa associated with amitriptyline.	2005 Aug	16040888
Role of histamine in airway remodeling of asthmatic guinea pig.	2005 Dec 25	16344897
Weak inhibitors protect cholinesterases from strong inhibitors (paraoxon): in vitro effect of ranitidine.	2005 Jan-Feb	15669026
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Intracerebroventricular effects of histaminergic agents on morphine-induced anxiolysis in the elevated plus-maze in rats.	2005 Nov	16236138
Excitatory effect of histamine on neuronal activity of rat globus pallidus by activation of H2 receptors in vitro.	2005 Nov	16143415
A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters.	2005 Oct	16006492
Antisecretory and antiulcer activity of Asparagus racemosus Willd. against indomethacin plus phyloric ligation-induced gastric ulcer in rats.	2006	17135157
Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes.	2006 Aug	16723495
Attenuation of indomethacin- and HCl/ethanol-induced oxidative gastric mucosa damage in rats by kolaviron, a natural biflavonoid of Garcinia kola seed.	2006 Jan	16397915
Coagulation-dependent gene expression and liver injury in rats given lipopolysaccharide with ranitidine but not with famotidine.	2006 May	16401727
Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats.	2007 Sep	17895592
Severe hypomagnesaemia due to lansoprazole.	2009	22180759
Drug-induced aseptic meningitis, sensorineural hearing loss and vestibulopaty.	2010 Sep	20977110
Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats.	2011 Mar	21116686
Discovery of two clinical histamine H(3) receptor antagonists: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764).	2011 Nov 10	21928839
The mediation of the central histaminergic system in the pressor effect of intracerebroventricularly injected melittin, a phospholipase A2 activator, in normotensive rats.	2012 Oct-Nov	22995146
Gastroprotective effects of goniothalamin against ethanol and indomethacin-induced gastric lesions in rats: Role of prostaglandins, nitric oxide and sulfhydryl compounds.	2014 Dec 5	25451594
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014 Jan	24085192

Patents

Sample Use Guides

In Vivo Use Guide

150 mg twice daily (tablets or syrup)

Route of Administration: Oral

In Vitro Use Guide

10uM ranitidine partially suppresses histamine-elicited signaling in human tubular epithelial cells

Substance Class	Chemical Created by `admin` on `Fri Dec 16 19:38:28 UTC 2022` Edited by `admin` on `Fri Dec 16 19:38:28 UTC 2022`
Record UNII	884KT10YB7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RANITIDINE

Official Name

English

RANITIDINE [VANDF]

Common Name

English

RANITIDINE [MI]

Common Name

English

RANITIDINE [MART.]

Common Name

English

RANITIDINE [ORANGE BOOK]

Common Name

English

RANITIDINE [USAN]

Common Name

English

NSC-757851

Code

English

Ranitidine [WHO-DD]

Common Name

English

RANITIDINE [HSDB]

Common Name

English

ranitidine [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

A02BA02