Diphemanil Methylsulfate

Identification

Name
Diphemanil Methylsulfate
Accession Number
DB00729  (APRD00928)
Type
Small Molecule
Groups
Approved, Vet Approved, Withdrawn
Description

Diphemanil Methylsulfate is a quaternary ammonium anticholinergic. It binds muscarinic acetycholine receptors and thereby decreases secretory excretion of stomach acids as well as saliva and sweat.

Structure
Thumb
Synonyms
  • 4-(Diphenylmethylene)-1,1-dimethylpiperidinium methyl sulfate
  • Diphemanil methosulfate
  • Diphemanil methylsulfat
  • Diphemanil metilsulfate
  • Diphemanili metilsulfas
  • Métilsulfate de Diphémanil
  • Metilsulfato de difemanilo
  • N,N-Dimethyl-4-piperidylidene-1,1-diphenylmethane methylsulfate
  • P-(alpha-Phenylbenzylidene)-1,1-dimethylpiperidinium methyl sulfate
  • Vagophemanil
International/Other Brands
Demotil (Pharmacia) / Prantal (Schering-Plough) / Prentol (Essex)
Categories
UNII
W2ZG23MGYI
CAS number
62-97-5
Weight
Average: 389.508
Monoisotopic: 389.166079047
Chemical Formula
C21H27NO4S
InChI Key
BREMLQBSKCSNNH-UHFFFAOYSA-M
InChI
InChI=1S/C20H24N.CH4O4S/c1-21(2)15-13-19(14-16-21)20(17-9-5-3-6-10-17)18-11-7-4-8-12-18;1-5-6(2,3)4/h3-12H,13-16H2,1-2H3;1H3,(H,2,3,4)/q+1;/p-1
IUPAC Name
4-(diphenylmethylidene)-1,1-dimethylpiperidin-1-ium methyl sulfate
SMILES
COS([O-])(=O)=O.C[N+]1(C)CCC(CC1)=C(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

Used in the treatment of peptic ulcer, gastric hyperacidity, and hypermotility in gastritis and pylorospasm, and in the treatment of hyperhidrosis (excessive perspiration).

Structured Indications
Not Available
Pharmacodynamics

Diphemanil Methylsulfate is a quaternary ammonium anticholinergic. It binds muscarinic acetycholine receptors and thereby decreases secretory excretion of stomach acids as well as saliva and sweat.

Mechanism of action

Diphemanil Methylsulfate exerts its action by primarily binding the muscarinic M3 receptor. M3 receptors are located in the smooth muscles of the blood vessels, as well as in the lungs. This means they cause vasodilation and bronchoconstriction. They are also in the smooth muscles of the gastrointestinal tract (GIT), which help in increasing intestinal motility and dilating sphincters. The M3 receptors are also located in many glands which help to stimulate secretion in salivary glands and other glands of the body.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M3
antagonist
Human
Absorption

Poorly absorbed from the gastrointestinal tract with an absolute bioavailability of 15 to 25%.

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
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Sperber, N., Villani, F.J. and Papa, D.; U.S. Patent 2,739,968; March 27,1956; assigned to Schering Corporation.

General References
Not Available
External Links
Human Metabolome Database
HMDB14867
PubChem Compound
6126
PubChem Substance
46506069
ChemSpider
5896
ChEBI
59782
ChEMBL
CHEMBL1200880
Therapeutic Targets Database
DAP001130
PharmGKB
PA164748388

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Schering corp sub schering plough corp
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)196-197Sperber, N., Villani, F.J. and Papa, D.; U.S. Patent 2,739,968; March 27,1956; assigned to Schering Corporation.
logP2.57Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000204 mg/mLALOGPS
logP1.12ALOGPS
logP-0.15ChemAxon
logS-6.3ALOGPS
Physiological Charge1ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity111.69 m3·mol-1ChemAxon
Polarizability33.56 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7038
Blood Brain Barrier+0.833
Caco-2 permeable-0.5676
P-glycoprotein substrateSubstrate0.7646
P-glycoprotein inhibitor IInhibitor0.6935
P-glycoprotein inhibitor IINon-inhibitor0.9637
Renal organic cation transporterNon-inhibitor0.5581
CYP450 2C9 substrateNon-substrate0.881
CYP450 2D6 substrateNon-substrate0.791
CYP450 3A4 substrateSubstrate0.5871
CYP450 1A2 substrateNon-inhibitor0.7637
CYP450 2C9 inhibitorNon-inhibitor0.7642
CYP450 2D6 inhibitorNon-inhibitor0.8142
CYP450 2C19 inhibitorNon-inhibitor0.7145
CYP450 3A4 inhibitorNon-inhibitor0.8236
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8619
Ames testNon AMES toxic0.5415
CarcinogenicityCarcinogens 0.5205
BiodegradationReady biodegradable0.9789
Rat acute toxicity2.6718 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.883
hERG inhibition (predictor II)Non-inhibitor0.5373
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Sulfuric acid monoesters / Piperidines / Alkyl sulfates / Tetraalkylammonium salts / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Diphenylmethane / Piperidine / Sulfuric acid monoester / Sulfate-ester / Sulfuric acid ester / Alkyl sulfate / Organic sulfuric acid or derivatives / Quaternary ammonium salt / Tetraalkylammonium salt / Azacycle
show 11 more
Molecular Framework
Not Available
External Descriptors
piperidines, quaternary ammonium salt (CHEBI:59782)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:42