Identification

Name
Chlormezanone
Accession Number
DB01178  (APRD00865)
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

A non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm. [PubChem]

Structure
Thumb
Synonyms
  • (+-)-Chlormezanone
  • (±)-chlormezanone
  • 2-(P-Chlorophenyl)tetrahydro-3-methyl-4H-1,3-thiazin-4-one 1,1-dioxide
  • 2-(P-Chlorphenyl)-3-methyl-1,3-perhydrothiazin-4-on-1,1-dioxide
  • Chlormethazanone
  • Chlormezanona
  • Chlormezanone
  • Chlormezanonum
  • Clormezanona
International/Other Brands
Fenaprim / Trancopal (WinthropSreon)
Categories
UNII
GP568V9G19
CAS number
80-77-3
Weight
Average: 273.736
Monoisotopic: 273.022641652
Chemical Formula
C11H12ClNO3S
InChI Key
WEQAYVWKMWHEJO-UHFFFAOYSA-N
InChI
InChI=1S/C11H12ClNO3S/c1-13-10(14)6-7-17(15,16)11(13)8-2-4-9(12)5-3-8/h2-5,11H,6-7H2,1H3
IUPAC Name
2-(4-chlorophenyl)-3-methyl-1λ⁶,3-thiazinane-1,1,4-trione
SMILES
CN1C(C2=CC=C(Cl)C=C2)S(=O)(=O)CCC1=O

Pharmacology

Indication

Used in the management of anxiety and in the treatment of muscle spasm.

Pharmacodynamics

Chlormezanone is a non-benzodiazepine muscle relaxant. It was discontinued worldwide in 1996 by its manufacturer due to confirmed serious and rare cutaneous reactions (toxic epidermal necrolysis).

Mechanism of action

Chlormezanone binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.

TargetActionsOrganism
ATranslocator protein
agonist
Human
Absorption
Not Available
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

Symptoms of overdose include drowsiness, weakness, nausea, dizziness, abdominal pain, cerebral oedema and renal tubular necrosis, hyperglycaemia and hypoglycaemia, liver damage, encephalopathy, coma and death.

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

Interactions

Drug Interactions
DrugInteraction
7-NitroindazoleThe risk or severity of adverse effects can be increased when Chlormezanone is combined with 7-Nitroindazole.
AcepromazineThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Aceprometazine.
AdipiplonThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Adipiplon.
AgomelatineThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Agomelatine.
AlaproclateThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Alaproclate.
AlfaxaloneThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Alfaxalone.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Chlormezanone.
AlimemazineThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Alimemazine.
AllopregnanoloneThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Allopregnanolone.
Food Interactions
Not Available

References

General References
  1. Wollina U, Hipler UC, Seeling A, Oelschlager H: Investigations of interactions of chlormezanone racemate and its enantiomers on human keratinocytes and human leucoytes in vitro. Skin Pharmacol Physiol. 2005 May-Jun;18(3):132-8. [PubMed:15897685]
  2. Seeling A, Oelschlager H, Rothley D: [Important pharmaceutical-chemical characteristics of the central muscle relaxant chlormezanone]. Pharmazie. 2000 Apr;55(4):293-6. [PubMed:10798243]
  3. Oelschlager H, Klinger W, Rothley D, Seeling A, Bockhard H, Hofmann B, Machts H, Riederer H, Rackur H: [Cleavage and biotransformation of the central muscle relaxant chlormezanone]. Pharmazie. 1998 Sep;53(9):620-4. [PubMed:9770210]
  4. Gautier V, Vincon G, Demotes-Mainard F, Albin H: [Pharmacokinetics of chlormezanone in healthy volunteers]. Therapie. 1990 Jul-Aug;45(4):315-9. [PubMed:2399514]
External Links
Human Metabolome Database
HMDB0015309
KEGG Drug
D00268
PubChem Compound
2717
PubChem Substance
46505352
ChemSpider
2616
ChEBI
3619
ChEMBL
CHEMBL1200714
Therapeutic Targets Database
DAP001252
PharmGKB
PA448939
Wikipedia
Chlormezanone
ATC Codes
M03BB02 — ChlormezanoneM03BB72 — Chlormezanone, combinations with psycholepticsM03BB52 — Chlormezanone, combinations excl. psycholeptics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)116.2-118.6Merck Index 2072
water solubility2500 mg/L (at 25 °C)MERCK INDEX (1996)
logP1.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.61 mg/mLALOGPS
logP0.84ALOGPS
logP0.92ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)19.07ChemAxon
pKa (Strongest Basic)-2.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area54.45 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity64.88 m3·mol-1ChemAxon
Polarizability25.89 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9167
Blood Brain Barrier+0.9383
Caco-2 permeable-0.5597
P-glycoprotein substrateNon-substrate0.6347
P-glycoprotein inhibitor INon-inhibitor0.6885
P-glycoprotein inhibitor IINon-inhibitor0.9959
Renal organic cation transporterNon-inhibitor0.7164
CYP450 2C9 substrateNon-substrate0.6022
CYP450 2D6 substrateNon-substrate0.7983
CYP450 3A4 substrateSubstrate0.6616
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9375
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5186
Ames testNon AMES toxic0.6263
CarcinogenicityNon-carcinogens0.7622
BiodegradationNot ready biodegradable0.6329
Rat acute toxicity2.6246 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9892
hERG inhibition (predictor II)Non-inhibitor0.7018
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
Mass Spectrum (Electron Ionization)MSsplash10-0udi-7900000000-6c729f1a3c9cb4241b45
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0kmi-0690000000-1392c5b54088e4de1cda
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as chlorobenzenes. These are compounds containing one or more chlorine atoms attached to a benzene moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Chlorobenzenes
Alternative Parents
Thiazinanes / Aryl chlorides / Tertiary carboxylic acid amides / Sulfones / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides / Organic oxides
show 2 more
Substituents
Chlorobenzene / Aryl chloride / Aryl halide / 1,3-thiazinane / Sulfone / Tertiary carboxylic acid amide / Carboxamide group / Lactam / Carboxylic acid derivative / Azacycle
show 12 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfone, lactam, monochlorobenzenes, 1,3-thiazine (CHEBI:3619)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Cholesterol binding
Specific Function
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in l...
Gene Name
TSPO
Uniprot ID
P30536
Uniprot Name
Translocator protein
Molecular Weight
18827.81 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 04:33