Identification

Name
Metiamide
Accession Number
DB08805
Type
Small Molecule
Groups
Experimental
Description

Metiamide is a histamine H2-receptor antagonist developed from another H2 antagonist, burimamide. It was an intermediate compound in the development of the successful anti-ulcer drug cimetidine.

Structure
Thumb
Synonyms
  • Methiamide
  • Metiamida
  • Metiamidum
External IDs
SK&F 92058
Categories
UNII
3K7670861M
CAS number
34839-70-8
Weight
Average: 244.38
Monoisotopic: 244.081637912
Chemical Formula
C9H16N4S2
InChI Key
FPBPLBWLMYGIQR-UHFFFAOYSA-N
InChI
InChI=1S/C9H16N4S2/c1-7-8(13-6-12-7)5-15-4-3-11-9(14)10-2/h6H,3-5H2,1-2H3,(H,12,13)(H2,10,11,14)
IUPAC Name
3-methyl-1-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl)thiourea
SMILES
CNC(=S)NCCSCC1=C(C)NC=N1

Pharmacology

Indication

Potential in the treatment and the management of acid-reflux disorders (GERD), peptic ulcer disease, heartburn, and acid indigestion.

Pharmacodynamics

Metiamide 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. Metiamide inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Metiamide include an increase in gastric bacterial flora such as nitrate-reducing organisms.

Mechanism of action

Metiamide 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.

TargetActionsOrganism
AHistamine H2 receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
PathwayCategory
Metiamide 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 Metiamide.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Metiamide.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Metiamide.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Metiamide.
AmphetamineAmphetamine may decrease the sedative and stimulatory activities of Metiamide.
AmprenavirMetiamide can cause a decrease in the absorption of Amprenavir resulting in a reduced serum concentration and potentially a decrease in efficacy.
AtazanavirMetiamide 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 Metiamide.
Benzylpenicilloyl PolylysineMetiamide may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Metiamide.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0061722
KEGG Drug
D05004
KEGG Compound
C07449
PubChem Compound
1548992
PubChem Substance
99445275
ChemSpider
1265996
BindingDB
50000382
ChEBI
6896
ChEMBL
CHEMBL275446
IUPHAR
1233
Guide to Pharmacology
GtP Drug Page
Wikipedia
Metiamide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0.50HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.0287 mg/mLALOGPS
logP0.5ALOGPS
logP0.34ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)12.48ChemAxon
pKa (Strongest Basic)6.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area52.74 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity70.4 m3·mol-1ChemAxon
Polarizability27.19 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9321
Blood Brain Barrier+0.8686
Caco-2 permeable-0.56
P-glycoprotein substrateSubstrate0.7606
P-glycoprotein inhibitor INon-inhibitor0.8835
P-glycoprotein inhibitor IINon-inhibitor0.9829
Renal organic cation transporterNon-inhibitor0.5167
CYP450 2C9 substrateNon-substrate0.8006
CYP450 2D6 substrateNon-substrate0.8241
CYP450 3A4 substrateNon-substrate0.6444
CYP450 1A2 substrateNon-inhibitor0.6219
CYP450 2C9 inhibitorNon-inhibitor0.7993
CYP450 2D6 inhibitorNon-inhibitor0.8256
CYP450 2C19 inhibitorNon-inhibitor0.5201
CYP450 3A4 inhibitorNon-inhibitor0.7244
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.821
Ames testNon AMES toxic0.6875
CarcinogenicityNon-carcinogens0.962
BiodegradationNot ready biodegradable0.9856
Rat acute toxicity2.2016 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7683
hERG inhibition (predictor II)Non-inhibitor0.7285
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 imidazoles. These are compounds containing an imidazole ring, which is an aromatic five-member ring with two nitrogen atoms at positions 1 and 3, and three carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Imidazoles
Alternative Parents
Heteroaromatic compounds / Thioureas / Sulfenyl compounds / Dialkylthioethers / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
Substituents
Heteroaromatic compound / Imidazole / Thiourea / Azacycle / Dialkylthioether / Sulfenyl compound / Thioether / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles (CHEBI:6896)

Targets

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. Black JW, Duncan WA, Emmett JC, Ganellin CR, Hesselbo T, Parsons ME, Wyllie JH: Metiamide--an orally active histamine H2-receptor antagonist. 1973. Agents Actions. 1994 Dec;43(3-4):91-5; discussion 96. [PubMed:7725982]

Drug created on October 15, 2010 16:20 / Updated on November 02, 2018 06:54