Identification

Name
Methantheline
Accession Number
DB00940  (APRD00751)
Type
Small Molecule
Groups
Approved, Investigational
Description

Methantheline is a synthetic antispasmodic. Antispasmodics are used to relieve cramps or spasms of the stomach, intestines, and bladder. Methantheline is used to treat intestine or stomach ulcers (peptic ulcer disease), intestine problems (irritable bowel syndrome), pancreatitis, gastritis, biliary dyskinesia, pylorosplasm, or urinary problems (reflex neurogenic bladder in children).

Structure
Thumb
Synonyms
  • Methantheline
  • Methanthelinium
  • Methanthelinum
External IDs
MTB 51
Product Ingredients
IngredientUNIICASInChI Key
Methantheline Bromide090519SAPF53-46-3PQMWYJDJHJQZDE-UHFFFAOYSA-M
International/Other Brands
Banthine / Vagantin
Categories
UNII
36EI79TX7I
CAS number
5818-17-7
Weight
Average: 340.436
Monoisotopic: 340.191268703
Chemical Formula
C21H26NO3
InChI Key
GZHFODJQISUKAY-UHFFFAOYSA-N
InChI
InChI=1S/C21H26NO3/c1-4-22(3,5-2)14-15-24-21(23)20-16-10-6-8-12-18(16)25-19-13-9-7-11-17(19)20/h6-13,20H,4-5,14-15H2,1-3H3/q+1
IUPAC Name
diethyl(methyl)[2-(9H-xanthene-9-carbonyloxy)ethyl]azanium
SMILES
CC[N+](C)(CC)CCOC(=O)C1C2=CC=CC=C2OC2=CC=CC=C12

Pharmacology

Indication

For the treatment of peptic ulcer disease, irritable bowel syndrome, pancreatitis, gastritis, biliary dyskinesia, pylorosplasm, and reflex neurogenic bladder in children.

Pharmacodynamics

Methantheline is a synthetic quarternary ammonium antimuscarinic used to relieve cramps or spasms of the stomach, intestines, and bladder. It can be used together with antacids or other medicines, such as H2-receptor antagonists, in the treatment of peptic ulcer. Methantheline inhibits muscarinic actions at postganglionic parasympathetic neuroeffector sites.

Mechanism of action

Methantheline inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These postganglionic receptor sites are present in the autonomic effector cells of the smooth muscle, cardiac muscle, sinoatrial and atrioventricular nodes, and exocrine glands. Depending on the dose, anticholinergics may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder.

TargetActionsOrganism
UMuscarinic acetylcholine receptor M1
antagonist
Human
AHistamine H2 receptor
antagonist
Human
Absorption

Rapidly absorbed.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic, by enzymatic hydrolysis.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose: blurred vision (continuing) or changes in near vision, clumsiness or unsteadiness, confusion, convulsions, difficulty in breathing, muscle weakness (severe), or tiredness (severe), dizziness, drowsiness (severe), dryness of mouth, nose, or throat (severe), fast heartbeat, fever, hallucinations, slurred speech, unusual excitement, nervousness, restlessness, or irritability, unusual warmth, dryness, and flushing of skin.

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

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Methantheline can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Methantheline.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Methantheline.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Methantheline.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Methantheline.
AbafunginMethantheline can cause a decrease in the absorption of Abafungin resulting in a reduced serum concentration and potentially a decrease in efficacy.
AclidiniumThe risk or severity of adverse effects can be increased when Methantheline is combined with Aclidinium.
AgmatineThe risk or severity of adverse effects can be increased when Methantheline is combined with Agmatine.
Ajulemic acidThe risk or severity of Tachycardia and drowsiness can be increased when Methantheline is combined with Ajulemic acid.
AlbaconazoleMethantheline can cause a decrease in the absorption of Albaconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015075
KEGG Compound
C07849
PubChem Compound
4097
PubChem Substance
46505807
ChemSpider
3955
ChEBI
6817
ChEMBL
CHEMBL1201264
Therapeutic Targets Database
DAP001109
PharmGKB
PA164747037
Wikipedia
Methantheline
ATC Codes
A03AB07 — Methantheline

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceNeurogenic Bladder Dysfunction1

Pharmacoeconomics

Manufacturers
  • Shire development inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000132 mg/mLALOGPS
logP0.5ALOGPS
logP-0.47ChemAxon
logS-6.4ALOGPS
pKa (Strongest Acidic)18.1ChemAxon
pKa (Strongest Basic)-7.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area35.53 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity110.42 m3·mol-1ChemAxon
Polarizability37.44 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9075
Blood Brain Barrier+0.9411
Caco-2 permeable+0.648
P-glycoprotein substrateSubstrate0.8327
P-glycoprotein inhibitor INon-inhibitor0.817
P-glycoprotein inhibitor IINon-inhibitor0.5977
Renal organic cation transporterNon-inhibitor0.5359
CYP450 2C9 substrateNon-substrate0.8214
CYP450 2D6 substrateNon-substrate0.599
CYP450 3A4 substrateSubstrate0.6801
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8476
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5637
Ames testNon AMES toxic0.8371
CarcinogenicityNon-carcinogens0.7407
BiodegradationNot ready biodegradable0.5863
Rat acute toxicity2.7675 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7426
hERG inhibition (predictor II)Inhibitor0.7318
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as xanthenes. These are polycyclic aromatic compounds containing a xanthene moiety, which consists of two benzene rings joined to each other by a pyran ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzopyrans
Sub Class
1-benzopyrans
Direct Parent
Xanthenes
Alternative Parents
Diarylethers / Benzenoids / Tetraalkylammonium salts / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Organopnictogen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives
show 3 more
Substituents
Xanthene / Diaryl ether / Benzenoid / Quaternary ammonium salt / Tetraalkylammonium salt / Carboxylic acid ester / Carboxylic acid derivative / Ether / Monocarboxylic acid or derivatives / Oxacycle
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
xanthenes (CHEBI:6817)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c 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
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 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]
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. Hough LB, Barker LA: Histamine H2-receptor antagonism by propantheline and derivatives. J Pharmacol Exp Ther. 1981 Nov;219(2):453-8. [PubMed:6116801]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:35