Identification
- Generic Name
- Metixene
- DrugBank Accession Number
- DB00340
- Background
Metixene (or methixene) is a anticholinergic used as an antiparkinsonian agent.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Metixene (DB00340)
- Weight
- Average: 309.468
Monoisotopic: 309.155120431 - Chemical Formula
- C20H23NS
- Synonyms
- Methixen
- Methixene
- Metisene
- Metixene
- Métixène
- Metixeno
- Metixenum
- External IDs
- 60 SJ 1977
Pharmacology
- Indication
Used for the symptomatic treatment of parkinsonism.
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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.
Target Actions Organism AMuscarinic acetylcholine receptor antagonistHumans - 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
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAclidinium The risk or severity of adverse effects can be increased when Metixene is combined with Aclidinium. Adenosine The risk or severity of Tachycardia can be increased when Metixene is combined with Adenosine. Alfentanil The risk or severity of adverse effects can be increased when Metixene is combined with Alfentanil. Alloin The therapeutic efficacy of Alloin can be decreased when used in combination with Metixene. Amantadine The risk or severity of adverse effects can be increased when Metixene is combined with Amantadine. Ambenonium The therapeutic efficacy of Metixene can be decreased when used in combination with Ambenonium. Amisulpride The therapeutic efficacy of Metixene can be decreased when used in combination with Amisulpride. Amitriptyline The risk or severity of adverse effects can be increased when Metixene is combined with Amitriptyline. Amitriptylinoxide The risk or severity of adverse effects can be increased when Metixene is combined with Amitriptylinoxide. Amobarbital The risk or severity of adverse effects can be increased when Metixene is combined with Amobarbital. 
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- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Metixene hydrochloride FRK5BSL54S 7081-40-5 RSXZRFHNNTTWCB-UHFFFAOYSA-N - International/Other Brands
- Cholinfall / Methixart / Tremaril / Tremarit
Categories
- ATC Codes
- N04AA03 — Metixene
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Amine / Aralkylamine / Aromatic heteropolycyclic compound / Aryl thioether / Azacycle / Benzenoid / Diarylthioether / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- piperidines, thioxanthenes (CHEBI:51024)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 32VY6L26ZW
- CAS number
- 4969-02-2
- 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-yl)methyl]piperidine
- SMILES
- CN1CCCC(CC2C3=CC=CC=C3SC3=CC=CC=C23)C1
References
- General References
- Link [Link]
- External Links
- Human Metabolome Database
- HMDB0014484
- KEGG Drug
- D01871
- PubChem Compound
- 4167
- PubChem Substance
- 46508970
- ChemSpider
- 4023
- BindingDB
- 79211
- 29682
- ChEBI
- 51024
- ChEMBL
- CHEMBL1201342
- Therapeutic Targets Database
- DAP000346
- PharmGKB
- PA164783811
- Wikipedia
- Metixene
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Novartis pharmaceuticals corp
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) < 25 °C PhysProp boiling point (°C) 173 °C at 7.00E-02 mm Hg PhysProp water solubility Soluble as HCl salt Not Available logP 4.7 Not Available - Predicted Properties
Property Value Source Water Solubility 0.000102 mg/mL ALOGPS logP 5.51 ALOGPS logP 5.06 Chemaxon logS -6.5 ALOGPS pKa (Strongest Basic) 9.34 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 3.24 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 97.17 m3·mol-1 Chemaxon Polarizability 35.65 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9825 Blood Brain Barrier + 0.995 Caco-2 permeable + 0.7863 P-glycoprotein substrate Substrate 0.81 P-glycoprotein inhibitor I Inhibitor 0.51 P-glycoprotein inhibitor II Inhibitor 0.8379 Renal organic cation transporter Inhibitor 0.8034 CYP450 2C9 substrate Non-substrate 0.7575 CYP450 2D6 substrate Substrate 0.7452 CYP450 3A4 substrate Non-substrate 0.5709 CYP450 1A2 substrate Non-inhibitor 0.8941 CYP450 2C9 inhibitor Non-inhibitor 0.9516 CYP450 2D6 inhibitor Inhibitor 0.9146 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.951 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6914 Ames test Non AMES toxic 0.8216 Carcinogenicity Non-carcinogens 0.9644 Biodegradation Not ready biodegradable 0.973 Rat acute toxicity 2.4059 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6823 hERG inhibition (predictor II) Inhibitor 0.8044
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- Curator comments
- Metixene has widespread antimuscarinic effects, but the data is currently limited on the exact receptors and their subunits.
- 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...
Components:
References
- Authors unspecified: Evaluation of an antispasmodic agent. Methixene hydrochloride (Trest). JAMA. 1966 Mar 7;195(10):851. doi: 10.1001/jama.1966.03100100103030. [Article]
- ABRUZZI W: THE USE OF METHIXENE HYDROCHLORIDE TO RELIEVE FUNCTIONAL GASTROINTESTINAL DISORDERS. J New Drugs. 1965 Mar-Apr;5(2):109-13. doi: 10.1002/j.1552-4604.1965.tb00233.x. [Article]
- Clarke S, Hay GA, Vas CJ: Therapeutic action of methixene hydrochloride on Parkinsonian tremor and a description of a new tremor-recording transducer. Br J Pharmacol Chemother. 1966 Feb;26(2):345-50. doi: 10.1111/j.1476-5381.1966.tb01913.x. [Article]
- Norris JW, Vas CJ: Mehixene hydrochloride and parkinsonian tremor. Acta Neurol Scand. 1967;43(4):535-8. doi: 10.1111/j.1600-0404.1967.tb05760.x. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 03, 2023 08:15