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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2020-02-26 21:40:25 UTC
HMDB IDHMDB0014835
Secondary Accession Numbers
  • HMDB14835
Metabolite Identification
Common NameTizanidine
DescriptionTizanidine is a short-acting drug for the management of spasticity. Tizanidine is an agonist at a2-adrenergic receptor sites and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. In animal models, tizanidine has no direct effect on skeletal muscle fibers or the neuromuscular junction, and no major effect on monosynaptic spinal reflexes. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons. Tizanidine has two major metabolites: (1) 5-chloro-4-(2-imidazolin-4-on-2-ylamino)-2,1,3-benzothiazdiazole and (2) 5-chloro-4-(2-imidazolin-4-on-2-ylamino)-2,1,3-benzothiadiazole (PMID: 9929503 , 19961320 ).
Structure
Data?1582753225
Synonyms
ValueSource
5-Chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazoleChEBI
TizanidinaChEBI
TizanidinumChEBI
SirdaludKegg
5-Chloro-4-(2-imidazolin-4-on-2-ylamino)-2,1,3-benzothiadiazoleHMDB
ZanaflexHMDB
Tizanidine monohydrochlorideHMDB
5-Chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazoleHMDB
Acorda brand OF tizanidine hydrochlorideHMDB
Novartis brand OF tizanidine hydrochlorideHMDB
Sanofi synthelabo brand OF tizanidine hydrochlorideHMDB
Tizanidine hydrochlorideHMDB
Chemical FormulaC9H8ClN5S
Average Molecular Weight253.711
Monoisotopic Molecular Weight253.018893678
IUPAC Name5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine
Traditional Nametizanidine
CAS Registry Number51322-75-9
SMILES
ClC1=C(NC2=NCCN2)C2=NSN=C2C=C1
InChI Identifier
InChI=1S/C9H8ClN5S/c10-5-1-2-6-8(15-16-14-6)7(5)13-9-11-3-4-12-9/h1-2H,3-4H2,(H2,11,12,13)
InChI KeyXFYDIVBRZNQMJC-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as benzothiadiazoles. These are heterocyclic aromatic compounds containing a benzene ring fused to a thiadiazole ring. Thiadiazole is a five-membered aromatic heterocycle made up of one sulfur atom and two nitrogen atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiadiazoles
Sub ClassNot Available
Direct ParentBenzothiadiazoles
Alternative Parents
Substituents
  • 2,1,3-benzothiadiazole
  • Aryl chloride
  • Aryl halide
  • Benzenoid
  • Azole
  • Heteroaromatic compound
  • 2-imidazoline
  • Thiadiazole
  • Guanidine
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Azacycle
  • Carboximidamide
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Source

Route of exposure

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.13 g/LNot Available
LogP1.4Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+CBM149.430932474
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.13 g/LALOGPS
logP10(1.6) g/LALOGPS
logP10(2.02) g/LChemAxon
logS10(-3.3) g/LALOGPS
pKa (Strongest Basic)7.49ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area62.2 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity64.77 m³·mol⁻¹ChemAxon
Polarizability23.97 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+147.37130932474
DeepCCS[M-H]-144.97630932474

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
TizanidineClC1=C(NC2=NCCN2)C2=NSN=C2C=C13476.4Standard polar33892256
TizanidineClC1=C(NC2=NCCN2)C2=NSN=C2C=C12408.8Standard non polar33892256
TizanidineClC1=C(NC2=NCCN2)C2=NSN=C2C=C12471.9Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Tizanidine,1TMS,isomer #1C[Si](C)(C)N(C1=NCCN1)C1=C(Cl)C=CC2=NSN=C122587.9Semi standard non polar33892256
Tizanidine,1TMS,isomer #1C[Si](C)(C)N(C1=NCCN1)C1=C(Cl)C=CC2=NSN=C122368.1Standard non polar33892256
Tizanidine,1TMS,isomer #1C[Si](C)(C)N(C1=NCCN1)C1=C(Cl)C=CC2=NSN=C124814.6Standard polar33892256
Tizanidine,1TMS,isomer #2C[Si](C)(C)N1CCN=C1NC1=C(Cl)C=CC2=NSN=C122622.0Semi standard non polar33892256
Tizanidine,1TMS,isomer #2C[Si](C)(C)N1CCN=C1NC1=C(Cl)C=CC2=NSN=C122484.5Standard non polar33892256
Tizanidine,1TMS,isomer #2C[Si](C)(C)N1CCN=C1NC1=C(Cl)C=CC2=NSN=C124332.7Standard polar33892256
Tizanidine,2TMS,isomer #1C[Si](C)(C)N1CCN=C1N(C1=C(Cl)C=CC2=NSN=C12)[Si](C)(C)C2544.4Semi standard non polar33892256
Tizanidine,2TMS,isomer #1C[Si](C)(C)N1CCN=C1N(C1=C(Cl)C=CC2=NSN=C12)[Si](C)(C)C2469.1Standard non polar33892256
Tizanidine,2TMS,isomer #1C[Si](C)(C)N1CCN=C1N(C1=C(Cl)C=CC2=NSN=C12)[Si](C)(C)C3869.1Standard polar33892256
Tizanidine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(C1=NCCN1)C1=C(Cl)C=CC2=NSN=C122774.6Semi standard non polar33892256
Tizanidine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(C1=NCCN1)C1=C(Cl)C=CC2=NSN=C122604.1Standard non polar33892256
Tizanidine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(C1=NCCN1)C1=C(Cl)C=CC2=NSN=C124806.4Standard polar33892256
Tizanidine,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1CCN=C1NC1=C(Cl)C=CC2=NSN=C122849.4Semi standard non polar33892256
Tizanidine,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1CCN=C1NC1=C(Cl)C=CC2=NSN=C122697.3Standard non polar33892256
Tizanidine,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1CCN=C1NC1=C(Cl)C=CC2=NSN=C124456.0Standard polar33892256
Tizanidine,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN=C1N(C1=C(Cl)C=CC2=NSN=C12)[Si](C)(C)C(C)(C)C2898.4Semi standard non polar33892256
Tizanidine,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN=C1N(C1=C(Cl)C=CC2=NSN=C12)[Si](C)(C)C(C)(C)C2909.8Standard non polar33892256
Tizanidine,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN=C1N(C1=C(Cl)C=CC2=NSN=C12)[Si](C)(C)C(C)(C)C3853.7Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Tizanidine GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-3960000000-3aca4c577af73cfa39972017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Tizanidine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
MSMass Spectrum (Electron Ionization)splash10-0udi-5490000000-5ee0610f321160b63c822014-09-20Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 10V, Positive-QTOFsplash10-0udi-0090000000-03af7132e7796b671fd22016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 20V, Positive-QTOFsplash10-0udi-2090000000-6ed6a84b177d1e4425ad2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 40V, Positive-QTOFsplash10-014i-9020000000-a1d6e32b00fde6ba39d42016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 10V, Negative-QTOFsplash10-0udi-0090000000-9ebe0248119b57c011752016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 20V, Negative-QTOFsplash10-0udi-1390000000-5ba6bc72d04cb138d4332016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 40V, Negative-QTOFsplash10-0a4i-2590000000-0e6b317aeab569aa3c972016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 10V, Positive-QTOFsplash10-0udi-0090000000-81fa3242a4171a3e23e82021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 20V, Positive-QTOFsplash10-0udi-0090000000-81fa3242a4171a3e23e82021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 40V, Positive-QTOFsplash10-000l-0930000000-89d08fc212d90d4e75ee2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 10V, Negative-QTOFsplash10-0udi-0090000000-809deeeabd14377046e02021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 20V, Negative-QTOFsplash10-001i-9000000000-c2fa753da65a4bac80a12021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tizanidine 40V, Negative-QTOFsplash10-001i-9000000000-a9ed1a171086d3aff4722021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00697 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00697 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00697
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5287
KEGG Compound IDC07452
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTizanidine
METLIN IDNot Available
PubChem Compound5487
PDB IDNot Available
ChEBI ID63629
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Shellenberger MK, Groves L, Shah J, Novack GD: A controlled pharmacokinetic evaluation of tizanidine and baclofen at steady state. Drug Metab Dispos. 1999 Feb;27(2):201-4. [PubMed:9929503 ]
  2. Zhou SF, Wang B, Yang LP, Liu JP: Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug Metab Rev. 2010 May;42(2):268-354. doi: 10.3109/03602530903286476. [PubMed:19961320 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  3. Shellenberger MK, Groves L, Shah J, Novack GD: A controlled pharmacokinetic evaluation of tizanidine and baclofen at steady state. Drug Metab Dispos. 1999 Feb;27(2):201-4. [PubMed:9929503 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular weight:
48956.3
References
  1. Piletz JE, Zhu H, Chikkala DN: Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J Pharmacol Exp Ther. 1996 Nov;279(2):694-702. [PubMed:8930173 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular weight:
49953.1
References
  1. Piletz JE, Zhu H, Chikkala DN: Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J Pharmacol Exp Ther. 1996 Nov;279(2):694-702. [PubMed:8930173 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular weight:
49521.6
References
  1. Piletz JE, Zhu H, Chikkala DN: Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J Pharmacol Exp Ther. 1996 Nov;279(2):694-702. [PubMed:8930173 ]