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Record Information
Version2.0
Creation Date2009-07-21 20:27:26 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2862
Identification
Common NameTizanidine
ClassSmall Molecule
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.
Compound Type
  • Adrenergic alpha-2 Receptor Agonist
  • Adrenergic alpha-Agonist
  • Amide
  • Amine
  • Analgesic
  • Anticonvulsant
  • Drug
  • Metabolite
  • Muscle Relaxant
  • Muscle Relaxant, Central
  • Muscle Relaxant, Skeletal
  • Neuromuscular Agent
  • Organic Compound
  • Organochloride
  • Parasympatholytic
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
5-Chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole
5-chloro-4-(2-imidazolin-4-on-2-ylamino)-2,1,3-benzothiadiazole
Cimbrar
Musant
Myores
Navizan
Relaxkov
Sirdalid
Sirdalud
Sirdalud MR
Sizolan
Spaslax
Telzanine
Ternelin
Tizadin
Tizaflex
Tizalud
Tizan
Tizanidin
Tizanidina
Tizanidinum
Zanaflex
Zanpeak
Zitanid
Chemical FormulaC9H8ClN5S
Average Molecular Mass253.711 g/mol
Monoisotopic Mass253.019 g/mol
CAS Registry Number51322-75-9
IUPAC Name5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine
Traditional Nametizanidine
SMILESClC1=C(NC2=NCCN2)C2=NSN=C2C=C1
InChI IdentifierInChI=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 KeyInChIKey=XFYDIVBRZNQMJC-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
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility1.33e-01 g/L
LogP1.4
Predicted Properties
PropertyValueSource
Water Solubility0.13 g/LALOGPS
logP1.6ALOGPS
logP2.02ChemAxon
logS-3.3ALOGPS
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
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-3960000000-3aca4c577af73cfa3997JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0090000000-03af7132e7796b671fd2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-2090000000-6ed6a84b177d1e4425adJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9020000000-a1d6e32b00fde6ba39d4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0090000000-9ebe0248119b57c01175JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-1390000000-5ba6bc72d04cb138d433JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-2590000000-0e6b317aeab569aa3c97JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0090000000-81fa3242a4171a3e23e8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0090000000-81fa3242a4171a3e23e8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000l-0930000000-89d08fc212d90d4e75eeJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0090000000-809deeeabd14377046e0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9000000000-c2fa753da65a4bac80a1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9000000000-a9ed1a171086d3aff472JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0udi-5490000000-5ee0610f321160b63c82JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureOral
Mechanism of ToxicityTizanidine reduces spasticity by increasing presynaptic inhibition of motor neurons through agonist action at a2-adrenergic receptor sites.
Metabolism Route of Elimination: Approximately 95% of an administered dose is metabolized. Half Life: 2.5 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the management of increased muscle tone associated with spasticity
Minimum Risk LevelNot Available
Health EffectsMay cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsNot Available
TreatmentShould overdose occur, basic steps to ensure the adequacy of an airway and the monitoring of cardiovascular and respiratory systems should be undertaken. In general, symptoms resolve within one to three days following discontinuation of tizanidine and administration of appropriate therapy. Due to the similar mechanism of action, symptoms and management of tizanidine overdose are similar to those following clonidine overdose. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00697
HMDB IDHMDB14835
PubChem Compound ID5487
ChEMBL IDCHEMBL1079
ChemSpider ID5287
KEGG IDC07452
UniProt IDNot Available
OMIM ID
ChEBI ID63629
BioCyc IDNot Available
CTD IDNot Available
Stitch IDTizanidine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTizanidine
References
Synthesis Reference

Pavel Hradil, Lubomir Kvapil, Martin Grepl, Jan Novotny, “METHOD FOR THE PREPARATION OF TIZANIDINE HYDROCHLORIDE.” U.S. Patent US20110263863, issued October 27, 2011.

MSDST3D2862.pdf
General References
  1. Drugs.com [Link]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Phosphatidylinositol binding
Specific Function:
Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways (By similarity). Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity). Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity). Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity). Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity). Inhibits lamellipodia formation, when overexpressed (By similarity). Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures.
Gene Name:
NISCH
Uniprot ID:
Q9Y2I1
Molecular Weight:
166627.105 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.028 uMNot AvailableBindingDB 50240671
References
  1. Rolon PA: Myxoglobulosis of the appendix. Int Surg. 1977 Jun-Jul;62(6-7):355-6. [893017 ]
  2. Nikolic K, Filipic S, Agbaba D: QSAR study of imidazoline antihypertensive drugs. Bioorg Med Chem. 2008 Aug 1;16(15):7134-40. doi: 10.1016/j.bmc.2008.06.051. Epub 2008 Jun 28. [18621536 ]
General Function:
Thioesterase binding
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:
48956.275 Da
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. [8930173 ]
General Function:
Epinephrine binding
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:
49565.8 Da
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. [8930173 ]
General Function:
Protein homodimerization activity
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:
49521.585 Da
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. [8930173 ]