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 2760	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 2760	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 2760

Conditions

Condition	Modality	Highest Phase	Product
Duodenal ulcer 41 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8360	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 66 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8360	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 60 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8360	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 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018703s065,019675s031,020251s016lbl.pdf	Primary	Approved 8360	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 1579 substrate 1709		inhibitor 1837 substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 506 OCT2 638 OCT3 149 MATE1 304 MATE2 261 CYP3A 211 CYP1A2 1509	OCT1 322 OCT2 348 OCT3 79 P-gp 1527 FMO3 66 FMO1 16 CYP1A2 1032 CYP2A6 523 CYP2C19 985 CYP2E1 648

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1673	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/	no
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/	no
CYP3A 295	inhibitor 3240 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 149	inhibitor 3240 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	weak [IC50 290 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers	weak
OCT2 639	inhibitor 3240 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes [IC50 114 uM]
MATE1 306	inhibitor 3240 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20053795	yes [IC50 18.9 uM]
OCT1 523	inhibitor 3240 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes [IC50 28 uM]
MATE2 261	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 25 uM]

Drug as victim

Target	Modality	Activity
FMO3 66	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	major
FMO1 16	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	minor
OCT2 348	substrate 3326 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	minor
CYP2A6 523	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
OCT3 79	substrate 3326 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	no
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
OCT1 322	substrate 3326 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes
P-gp 1527	substrate 3326 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
Histamine H2 antagonists and the nervous system.	1985 Dec	4072863
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
Mania associated with intravenous ranitidine therapy.	1987 Nov	3500517
Fatal renal and hepatic toxicity after treatment with diltiazem.	1987 Nov 14	3120959
First-degree atrioventricular block in a young duodenal ulcer patient treated with a standard oral dose of ranitidine.	1988 Jul	3177090
Reversible chorea due to ranitidine and cimetidine.	1988 Jul 16	2899203
Ranitidine and bradycardia.	1988 Mar	3341694
A dog model for acetaminophen-induced fulminant hepatic failure.	1989 Feb	2910762
Histamine release in the isolated vascularly perfused stomach of the rat: regulation by autoreceptors.	1989 Mar	2470453
Histamine release and SOD, allopurinol and ranitidine pretreatment in haemorrhagic shock in the rat.	1992	1285366
Ranitidine does not alter adinazolam pharmacokinetics or pharmacodynamics.	1992 Aug	1527233
Ranitidine pharmacokinetics and adverse central nervous system reactions.	1992 Nov	1444693
Ranitidine-related Stevens-Johnson syndrome in patients with severe liver diseases: a report of two cases.	2001 Apr	11354291
Proton pump inhibitors versus H2-antagonists: a meta-analysis of their efficacy in treating bleeding peptic ulcer.	2001 Jul	11421865
Management of heartburn in a large, randomized, community-based study: comparison of four therapeutic strategies.	2001 Jun	11419818
Effects of three H2-receptor antagonists (cimetidine, famotidine, ranitidine) on serum gastrin level.	2002	12503773
Functional analysis of histamine receptor subtypes involved in endothelium-mediated relaxation of the human uterine artery.	2002 Aug	12100006
Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials.	2002 Jul 15	12119060
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
Ranitidine treatment during a modest inflammatory response precipitates idiosyncrasy-like liver injury in rats.	2003 Oct	12893837
Involvement of substance P, CGRP and histamine in the hyperalgesia and cytokine upregulation induced by intraplantar injection of capsaicin in rats.	2004 Aug	15265675
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
Switching of H(2)-Receptor Antagonists to Over-the-Counter Status in Finland : Implications for Consumption and Adverse Effects.	2005	17523774
Drug specificity and intestinal membrane localization of human organic cation transporters (OCT).	2005 Dec 5	16263091
Weak inhibitors protect cholinesterases from strong inhibitors (paraoxon): in vitro effect of ranitidine.	2005 Jan-Feb	15669026
Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response.	2005 Jul	15995512
Mechanisms of action of leptin in preventing gastric ulcer.	2005 Jul 21	16015682
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
Weak inhibitors protect cholinesterases from strong inhibitors (paraoxon): in vitro effect of tiapride.	2005 Nov-Dec	16193528
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
In vitro availability of metformin in presence of h(2) receptor antagonists.	2006 Jan	16632449
Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats.	2006 Jan 3	16169175
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
Coagulation-dependent gene expression and liver injury in rats given lipopolysaccharide with ranitidine but not with famotidine.	2006 May	16401727
Novel role of famotidine in downregulation of matrix metalloproteinase-9 during protection of ethanol-induced acute gastric ulcer.	2007 Jul 15	17603938
Gastroprotective and antioxidant effects of amiodarone on indomethacin-induced gastric ulcers in rats.	2007 Nov	18087811
Severe hypomagnesaemia due to lansoprazole.	2009	22180759
Protective effect of histamine H2 receptor antagonist ranitidine against rotenone-induced apoptosis.	2009 Nov	19723537
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

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 `Wed Jul 05 23:41:37 UTC 2023` Edited by `admin` on `Wed Jul 05 23:41:37 UTC 2023`
Record UNII	884KT10YB7
Record Status	`Validated (UNII)`
Record Version

Download

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