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Approved, Vet approved, Withdrawn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).

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
DrugInteractionDrug group
AgmatineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Agmatine.Experimental, Investigational
AtropineThe risk or severity of adverse effects can be increased when Atropine is combined with Diphemanil Methylsulfate.Approved, Vet Approved
BenzatropineThe risk or severity of adverse effects can be increased when Benzatropine is combined with Diphemanil Methylsulfate.Approved
BisacodylThe therapeutic efficacy of Bisacodyl can be decreased when used in combination with Diphemanil Methylsulfate.Approved
BrompheniramineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Brompheniramine.Approved
BupropionThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Bupropion.Approved
CodeineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Codeine.Approved, Illicit
DextromethorphanThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Dextromethorphan.Approved
DiphenhydramineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with Diphemanil Methylsulfate.Approved, Investigational
DocusateThe therapeutic efficacy of Docusate can be decreased when used in combination with Diphemanil Methylsulfate.Approved
DoxylamineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Doxylamine.Approved, Vet Approved
FentanylThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FluoxetineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Fluoxetine.Approved, Vet Approved
GlycerinThe therapeutic efficacy of Glycerin can be decreased when used in combination with Diphemanil Methylsulfate.Approved, Investigational
HydrochlorothiazideThe serum concentration of Hydrochlorothiazide can be increased when it is combined with Diphemanil Methylsulfate.Approved, Vet Approved
HydrocodoneThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Hydrocodone.Approved, Illicit
HyoscyamineThe risk or severity of adverse effects can be increased when Hyoscyamine is combined with Diphemanil Methylsulfate.Approved
IpratropiumThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Ipratropium.Approved
LactuloseThe therapeutic efficacy of Lactulose can be decreased when used in combination with Diphemanil Methylsulfate.Approved
LamotrigineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Lamotrigine.Approved, Investigational
Magnesium carbonateThe therapeutic efficacy of Magnesium carbonate can be decreased when used in combination with Diphemanil Methylsulfate.Approved, Investigational
Magnesium citrateThe therapeutic efficacy of Magnesium citrate can be decreased when used in combination with Diphemanil Methylsulfate.Approved
Magnesium hydroxideThe therapeutic efficacy of Magnesium hydroxide can be decreased when used in combination with Diphemanil Methylsulfate.Approved, Investigational
Magnesium sulfateThe therapeutic efficacy of Magnesium sulfate can be decreased when used in combination with Diphemanil Methylsulfate.Approved, Investigational, Vet Approved
MetoclopramideThe therapeutic efficacy of Diphemanil Methylsulfate can be decreased when used in combination with Metoclopramide.Approved, Investigational
Mineral oilThe therapeutic efficacy of Mineral oil can be decreased when used in combination with Diphemanil Methylsulfate.Approved, Vet Approved
NicardipineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Nicardipine.Approved, Investigational
OtiloniumThe risk or severity of adverse effects can be increased when Otilonium is combined with Diphemanil Methylsulfate.Experimental, Investigational
OxycodoneThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Oxycodone.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Oxymorphone.Approved, Investigational, Vet Approved
ParoxetineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Paroxetine.Approved, Investigational
PhenobarbitalThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Phenobarbital.Approved, Investigational
Potassium ChlorideThe risk or severity of gastrointestinal ulceration can be increased when Diphemanil Methylsulfate is combined with Potassium Chloride.Approved, Withdrawn
PromethazineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Promethazine.Approved, Investigational
QuetiapineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Quetiapine.Approved
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Diphemanil Methylsulfate.Approved, Investigational
Sodium phosphate, monobasicThe therapeutic efficacy of Sodium phosphate, monobasic can be decreased when used in combination with Diphemanil Methylsulfate.Approved
TopiramateThe risk or severity of hyperthermia and oligohydrosis can be increased when Diphemanil Methylsulfate is combined with Topiramate.Approved
TramadolThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Tramadol.Approved, Investigational
TrimebutineThe risk or severity of adverse effects can be increased when Diphemanil Methylsulfate is combined with Trimebutine.Approved
TrospiumThe risk or severity of adverse effects can be increased when Trospium is combined with Diphemanil Methylsulfate.Approved
VecuroniumThe risk or severity of adverse effects can be increased when Vecuronium is combined with Diphemanil Methylsulfate.Approved
WIN 55212-2The risk or severity of Tachycardia and drowsiness can be increased when Diphemanil Methylsulfate is combined with WIN 55212-2.Experimental
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
HMDB0014867
PubChem Compound
6126
PubChem Substance
46506069
ChemSpider
5896
ChEBI
59782
ChEMBL
CHEMBL1200880
Therapeutic Targets Database
DAP001130
PharmGKB
PA164748388
Wikipedia
Diphemanil_Methylsulfate

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 August 02, 2018 04:26