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Identification
NameMetixene
Accession NumberDB00340  (APRD01101)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
Methixen
Methixene
Metisene
Metixeno
Metixenum
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CholinfallNot Available
MethixartNot Available
TremarilNot Available
TremaritNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Metixene hydrochloride
Thumb
  • InChI Key: RSXZRFHNNTTWCB-UHFFFAOYNA-N
  • Monoisotopic Mass: 345.13179817
  • Average Mass: 345.929
DBSALT000602
Categories
UNII32VY6L26ZW
CAS number4969-02-2
WeightAverage: 309.468
Monoisotopic: 309.155120431
Chemical FormulaC20H23NS
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiopyrans
Sub Class1-benzothiopyrans
Direct ParentThioxanthenes
Alternative Parents
Substituents
  • Thioxanthene
  • Diarylthioether
  • Aralkylamine
  • Benzenoid
  • Piperidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Thioether
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed for the symptomatic treatment of parkinsonism.
PharmacodynamicsMetixene 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 actionParkinsonism 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.
Related Articles
AbsorptionAbsorbed in the gastrointestinal tract following oral administration, however the extent of absorption is not known.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. Metabolism occurs via sulfoxydation and N-demethylation.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySigns 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point< 25 °CPhysProp
boiling point173 °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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Link [Link]
External Links
ATC CodesN04AA03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
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 action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM5
Uniprot ID:
P08912
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 action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then trigge...
Gene Name:
CHRM2
Uniprot ID:
P08172
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
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 ]
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Drug created on June 13, 2005 07:24 / Updated on November 24, 2015 12:35