Identification

Name
Roxatidine acetate
Accession Number
DB08806
Type
Small Molecule
Groups
Experimental
Description

Roxatidine acetate is a specific and competitive H2 receptor antagonist. It is currently approved in South Africa under the tradename Roxit.

Structure
Thumb
Synonyms
  • Pifatidine
Product Ingredients
IngredientUNIICASInChI Key
Roxatidine acetate hydrochloride60426GOR1E93793-83-0FEWCTJHCXOHWNL-UHFFFAOYSA-N
International/Other Brands
Roxit
Categories
UNII
ZUP3LSD0DO
CAS number
78628-28-1
Weight
Average: 348.4366
Monoisotopic: 348.204907394
Chemical Formula
C19H28N2O4
InChI Key
SMTZFNFIKUPEJC-UHFFFAOYSA-N
InChI
InChI=1S/C19H28N2O4/c1-16(22)25-15-19(23)20-9-6-12-24-18-8-5-7-17(13-18)14-21-10-3-2-4-11-21/h5,7-8,13H,2-4,6,9-12,14-15H2,1H3,(H,20,23)
IUPAC Name
({3-[3-(piperidin-1-ylmethyl)phenoxy]propyl}carbamoyl)methyl acetate
SMILES
CC(=O)OCC(=O)NCCCOC1=CC=CC(CN2CCCCC2)=C1

Pharmacology

Indication

For the treatment of disorders of the upper gastro-intestinal region that are due to an excess of hydrochloric acid in the gastric juice, i.e. duodenal ulcers, benign gastric ulcers. Also for prophylaxis of recurrent gastric and duodenal ulcers

Pharmacodynamics

Roxatidine acetate suppresses the effect of histamine on the parietal cells of the stomach (H2-receptor antagonist). This suppressive action is dose-dependent. As a result, the production and secretion, particularly of gastric acid, are reduced. Roxatidine acetate has no antiandrogenic effects and does not influence drug-metabolizing enzymes in the liver.

Mechanism of action

The H2 antagonists are competitive inhibitors of histamine at the parietal cell H2 receptor. They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms: histamine released by ECL cells in the stomach is blocked from binding on parietal cell H2 receptors which stimulate acid secretion, and other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells when the H2 receptors are blocked.

TargetActionsOrganism
AHistamine H2 receptor
antagonist
Human
Absorption

Well absorbed orally (80–90% bioavailability).

Volume of distribution
Not Available
Protein binding

5-7%

Metabolism

Roxatidine acetate is rapidly metabolised to the primary, active desacetyl metabolite.

Route of elimination
Not Available
Half life

5-6 hours

Clearance
Not Available
Toxicity

Oral, mouse LD50: 1000 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Roxatidine Acetate Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Roxatidine acetate.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Roxatidine acetate.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Roxatidine acetate.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Roxatidine acetate.
AmphetamineAmphetamine may decrease the sedative and stimulatory activities of Roxatidine acetate.
AmprenavirRoxatidine acetate can cause a decrease in the absorption of Amprenavir resulting in a reduced serum concentration and potentially a decrease in efficacy.
AtazanavirRoxatidine acetate can cause a decrease in the absorption of Atazanavir resulting in a reduced serum concentration and potentially a decrease in efficacy.
BenzphetamineBenzphetamine may decrease the sedative and stimulatory activities of Roxatidine acetate.
Benzylpenicilloyl PolylysineRoxatidine acetate may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Roxatidine acetate.
Food Interactions
Not Available

References

General References
  1. Murdoch D, McTavish D: Roxatidine acetate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic potential in peptic ulcer disease and related disorders. Drugs. 1991 Aug;42(2):240-60. [PubMed:1717223]
  2. Product Insert [Link]
External Links
Human Metabolome Database
HMDB0015695
KEGG Drug
D08495
PubChem Compound
5105
PubChem Substance
99445276
ChemSpider
4926
BindingDB
50404032
ChEBI
94758
ChEMBL
CHEMBL46102
PharmGKB
PA165958424
Wikipedia
Roxatidine_acetate
ATC Codes
A02BA06 — Roxatidine
MSDS
Download (1.19 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableCommunity Acquired Pneumonia (CAP) / Gastro-esophageal Reflux Disease (GERD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)145-146 for HCl saltMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0612 mg/mLALOGPS
logP2.27ALOGPS
logP1.31ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)14.88ChemAxon
pKa (Strongest Basic)8.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area67.87 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity96.32 m3·mol-1ChemAxon
Polarizability39.26 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9475
Blood Brain Barrier+0.8366
Caco-2 permeable-0.6032
P-glycoprotein substrateSubstrate0.7781
P-glycoprotein inhibitor IInhibitor0.7868
P-glycoprotein inhibitor IINon-inhibitor0.675
Renal organic cation transporterNon-inhibitor0.645
CYP450 2C9 substrateNon-substrate0.7803
CYP450 2D6 substrateNon-substrate0.8415
CYP450 3A4 substrateSubstrate0.5264
CYP450 1A2 substrateNon-inhibitor0.9143
CYP450 2C9 inhibitorNon-inhibitor0.8237
CYP450 2D6 inhibitorNon-inhibitor0.6876
CYP450 2C19 inhibitorNon-inhibitor0.7797
CYP450 3A4 inhibitorNon-inhibitor0.9203
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6467
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9324
BiodegradationNot ready biodegradable0.5199
Rat acute toxicity2.0100 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8833
hERG inhibition (predictor II)Inhibitor0.5448
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-benzylpiperidines. These are heterocyclic Compounds containing a piperidine ring conjugated to a benzyl group through one nitrogen ring atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Benzylpiperidines
Direct Parent
N-benzylpiperidines
Alternative Parents
Benzylamines / Phenol ethers / Phenoxy compounds / Phenylmethylamines / Alkyl aryl ethers / Aralkylamines / Amino acids and derivatives / Carboxylic acid esters / Secondary carboxylic acid amides / Trialkylamines
show 6 more
Substituents
N-benzylpiperidine / Phenoxy compound / Benzylamine / Phenol ether / Phenylmethylamine / Alkyl aryl ether / Aralkylamine / Monocyclic benzene moiety / Benzenoid / Amino acid or derivatives
show 19 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Details
1. Histamine H2 receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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 diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Agrawal SS, Alvin Jose M: Roxatidine, an H(2) receptor blocker, is an estrogenic compound--experimental evidence. Syst Biol Reprod Med. 2010 Aug;56(4):286-91. doi: 10.3109/19396368.2010.496894. [PubMed:20718616]

Drug created on October 18, 2010 16:57 / Updated on November 02, 2018 08:43