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.

Structured Indications
Not Available
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
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Metiamide.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Metiamide.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Metiamide.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Metiamide.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Metiamide.Approved, Illicit
AtazanavirThe serum concentration of Atazanavir can be decreased when it is combined with Metiamide.Approved, Investigational
BenzphetamineBenzphetamine may decrease the sedative activities of Metiamide.Approved, Illicit
Benzylpenicilloyl PolylysineMetiamide may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Metiamide.Approved
BosutinibThe serum concentration of Bosutinib can be decreased when it is combined with Metiamide.Approved
CefditorenThe serum concentration of Cefditoren can be decreased when it is combined with Metiamide.Approved
CefpodoximeMetiamide can cause a decrease in the absorption of Cefpodoxime resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Vet Approved
CefuroximeMetiamide can cause a decrease in the absorption of Cefuroxime resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ChlorphentermineChlorphentermine may decrease the sedative activities of Metiamide.Illicit, Withdrawn
CysteamineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Metiamide.Approved, Investigational
DabrafenibThe serum concentration of Dabrafenib can be decreased when it is combined with Metiamide.Approved
DasatinibMetiamide can cause a decrease in the absorption of Dasatinib resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
DelavirdineMetiamide can cause a decrease in the absorption of Delavirdine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DexmethylphenidateMetiamide can cause an increase in the absorption of Dexmethylphenidate resulting in an increased serum concentration and potentially a worsening of adverse effects.Approved
DextroamphetamineDextroamphetamine may decrease the sedative activities of Metiamide.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Metiamide.Approved, Illicit
ErlotinibThe serum concentration of Erlotinib can be decreased when it is combined with Metiamide.Approved, Investigational
Ferric CarboxymaltoseMetiamide can cause a decrease in the absorption of Ferric Carboxymaltose resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Ferric CitrateMetiamide can cause a decrease in the absorption of Ferric Citrate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
Ferric pyrophosphateMetiamide can cause a decrease in the absorption of Ferric pyrophosphate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
FosamprenavirThe serum concentration of Fosamprenavir can be decreased when it is combined with Metiamide.Approved
GefitinibThe serum concentration of Gefitinib can be decreased when it is combined with Metiamide.Approved, Investigational
GepefrineGepefrine may decrease the sedative activities of Metiamide.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Metiamide.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Metiamide.Approved
IndinavirThe serum concentration of Indinavir can be decreased when it is combined with Metiamide.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Metiamide.Approved
IronMetiamide can cause a decrease in the absorption of Iron resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Iron DextranMetiamide can cause a decrease in the absorption of Iron Dextran resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Vet Approved
Iron saccharateMetiamide can cause a decrease in the absorption of Iron saccharate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ItraconazoleThe serum concentration of Itraconazole can be decreased when it is combined with Metiamide.Approved, Investigational
KetoconazoleThe serum concentration of Ketoconazole can be decreased when it is combined with Metiamide.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be decreased when it is combined with Metiamide.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Metiamide.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Metiamide.Investigational
MephentermineMephentermine may decrease the sedative activities of Metiamide.Approved
MesalazineThe therapeutic efficacy of Mesalazine can be decreased when used in combination with Metiamide.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Metiamide.Approved, Illicit
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Metiamide.Experimental
MethylphenidateMetiamide can cause an increase in the absorption of Methylphenidate resulting in an increased serum concentration and potentially a worsening of adverse effects.Approved, Investigational
MidomafetamineMidomafetamine may decrease the sedative activities of Metiamide.Experimental, Illicit, Investigational
MMDAMMDA may decrease the sedative activities of Metiamide.Experimental, Illicit
NelfinavirThe serum concentration of Nelfinavir can be decreased when it is combined with Metiamide.Approved
NilotinibThe serum concentration of Nilotinib can be decreased when it is combined with Metiamide.Approved, Investigational
PazopanibMetiamide can cause a decrease in the absorption of Pazopanib resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
PhenterminePhentermine may decrease the sedative activities of Metiamide.Approved, Illicit
PosaconazoleThe serum concentration of Posaconazole can be decreased when it is combined with Metiamide.Approved, Investigational, Vet Approved
PseudoephedrinePseudoephedrine may decrease the sedative activities of Metiamide.Approved
RisedronateMetiamide can cause an increase in the absorption of Risedronate resulting in an increased serum concentration and potentially a worsening of adverse effects.Approved, Investigational
RitobegronRitobegron may decrease the sedative activities of Metiamide.Investigational
SaquinavirThe serum concentration of Saquinavir can be increased when it is combined with Metiamide.Approved, Investigational
VareniclineThe serum concentration of Varenicline can be increased when it is combined with Metiamide.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB61722
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 09, 2017 04:40