Identification

Name
Metixene
Accession Number
DB00340  (APRD01101)
Type
Small Molecule
Groups
Approved
Description

Metixene (or methixene) is a anticholinergic used as an antiparkinsonian agent.

Structure
Thumb
Synonyms
  • Methixen
  • Methixene
  • Metisene
  • Metixeno
  • Metixenum
Product Ingredients
IngredientUNIICASInChI Key
Metixene hydrochloride84L8XK6N1G7081-40-5RSXZRFHNNTTWCB-UHFFFAOYSA-N
International/Other Brands
Cholinfall / Methixart / Tremaril / Tremarit
Categories
UNII
32VY6L26ZW
CAS number
4969-02-2
Weight
Average: 309.468
Monoisotopic: 309.155120431
Chemical Formula
C20H23NS
InChI Key
MJFJKKXQDNNUJF-UHFFFAOYSA-N
InChI
InChI=1S/C20H23NS/c1-21-12-6-7-15(14-21)13-18-16-8-2-4-10-19(16)22-20-11-5-3-9-17(18)20/h2-5,8-11,15,18H,6-7,12-14H2,1H3
IUPAC Name
1-methyl-3-(9H-thioxanthen-9-ylmethyl)piperidine
SMILES
CN1CCCC(CC2C3=CC=CC=C3SC3=CC=CC=C23)C1

Pharmacology

Indication

Used for the symptomatic treatment of parkinsonism.

Pharmacodynamics

Metixene is a tertiary antimuscarinic with actions similar to those of atropine; it also has antihistaminic and direct antispasmodic properties. It is used for the symptomatic treatment of parkinsonism, including the alleviation of the extrapyramidal syndrome induced by other drugs such as phenothiazines, but, like other antimuscarinics, it is of no value against tardive dyskinesias. Metixene has been discontinued.

Mechanism of action

Parkinsonism is thought to result from an imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic) systems in the corpus striatum. The mechanism of action of centrally active anticholinergic drugs such as metixene is considered to relate to competitive antagonism of acetylcholine at muscarinic receptors in the corpus striatum, which then restores the balance.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M1
antagonist
Human
AMuscarinic acetylcholine receptor M4
antagonist
Human
AMuscarinic acetylcholine receptor M5
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
Absorption

Absorbed in the gastrointestinal tract following oral administration, however the extent of absorption is not known.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic. Metabolism occurs via sulfoxydation and N-demethylation.

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

Signs of overdose include dilated and sluggish pupils, warm, dry skin, facial flushing, decreased secretions of the mouth, pharynx, nose, and bronchi, foul-smelling breath, elevated temperature, tachycardia, cardiac arrhythmias, decreased bowel sounds, urinary retention, delirium, disorientation, anxiety, hallucinations, illusions, confusion, incoherence, agitation, hyperactivity, ataxia, loss of memory, paranoia, combativeness, and seizures.

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

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Metixene can be decreased when used in combination with 1,10-Phenanthroline.
AclidiniumThe risk or severity of adverse effects can be increased when Metixene is combined with Aclidinium.
AgmatineThe risk or severity of adverse effects can be increased when Metixene is combined with Agmatine.
Ajulemic acidThe risk or severity of Tachycardia and drowsiness can be increased when Metixene is combined with Ajulemic acid.
AlcuroniumThe risk or severity of adverse effects can be increased when Metixene is combined with Alcuronium.
AlfentanilThe risk or severity of adverse effects can be increased when Metixene is combined with Alfentanil.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Metixene is combined with Alphacetylmethadol.
AlphaprodineThe risk or severity of adverse effects can be increased when Metixene is combined with Alphaprodine.
Aluminum sulfateThe therapeutic efficacy of Aluminum sulfate can be decreased when used in combination with Metixene.
AmbenoniumThe therapeutic efficacy of Metixene can be decreased when used in combination with Ambenonium.
Food Interactions
Not Available

References

General References
  1. Link [Link]
External Links
Human Metabolome Database
HMDB0014484
KEGG Drug
D01871
PubChem Compound
4167
PubChem Substance
46508970
ChemSpider
4023
BindingDB
79211
ChEBI
51024
ChEMBL
CHEMBL1201342
Therapeutic Targets Database
DAP000346
PharmGKB
PA164783811
Wikipedia
Metixene
ATC Codes
N04AA03 — Metixene

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)< 25 °CPhysProp
boiling point (°C)173 °C at 7.00E-02 mm HgPhysProp
water solubilitySoluble as HCl saltNot Available
logP4.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000102 mg/mLALOGPS
logP5.51ALOGPS
logP5.06ChemAxon
logS-6.5ALOGPS
pKa (Strongest Basic)9.34ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity97.17 m3·mol-1ChemAxon
Polarizability35.67 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9825
Blood Brain Barrier+0.995
Caco-2 permeable+0.7863
P-glycoprotein substrateSubstrate0.81
P-glycoprotein inhibitor IInhibitor0.51
P-glycoprotein inhibitor IIInhibitor0.8379
Renal organic cation transporterInhibitor0.8034
CYP450 2C9 substrateNon-substrate0.7575
CYP450 2D6 substrateSubstrate0.7452
CYP450 3A4 substrateNon-substrate0.5709
CYP450 1A2 substrateNon-inhibitor0.8941
CYP450 2C9 inhibitorNon-inhibitor0.9516
CYP450 2D6 inhibitorInhibitor0.9146
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.951
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6914
Ames testNon AMES toxic0.8216
CarcinogenicityNon-carcinogens0.9644
BiodegradationNot ready biodegradable0.973
Rat acute toxicity2.4059 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6823
hERG inhibition (predictor II)Inhibitor0.8044
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 thioxanthenes. These are organic polycyclic compounds containing a thioxanthene moiety, which is an aromatic tricycle derived from xanthene by replacing the oxygen atom with a sulfur atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiopyrans
Sub Class
1-benzothiopyrans
Direct Parent
Thioxanthenes
Alternative Parents
Diarylthioethers / Aralkylamines / Piperidines / Benzenoids / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Thioxanthene / Diarylthioether / Aryl thioether / Aralkylamine / Piperidine / Benzenoid / Tertiary amine / Tertiary aliphatic amine / Thioether / Azacycle
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, thioxanthenes (CHEBI:51024)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
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
Guanyl-nucleotide exchange factor 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
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 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
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
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled acetylcholine 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
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 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
Unknown
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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:40