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Identification
NameTizanidine
Accession NumberDB00697  (APRD00128)
Typesmall molecule
Groupsapproved
Description

Tizanidine 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.

Structure
Thumb
Synonyms
SynonymLanguageCode
5-Chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazoleNot AvailableNot Available
TizanidinGermanINN
TizanidinaSpanishINN
TizanidineFrenchINN
TizanidinumLatinINN
Salts
Name/CAS Structure Properties
Tizanidine Hydrochloride
Thumb
  • InChI Key: ZWUKMNZJRDGCTQ-UHFFFAOYSA-N
  • Monoisotopic Mass: 288.995571417
  • Average Mass: 290.172
DBSALT000550
Brand names
NameCompany
CimbrarEuroetika
MusantActavis
MyoresMeprofarm
NavizanCaber
RelaxkovBlaskov
SirdalidNovartis
SirdaludNovartis
Sirdalud MRNovartis
SizolanDr. Reddy's
SpaslaxPanion & BF
TelzanineNisshin Seiyaku
TernelinNovartis
TizadinACL
TizaflexActavis
TizaludOpsonin
TizanSun
ZanaflexAcorda
ZanpeakTatsumi Kagaku
ZitanidNovell
Brand mixtures
Brand NameIngredients
Acent-TZTizanidine and Aceclofenac
Amiox-KTizanidine and Ketorolac
Amiox-PTizanidine and Paracetamol
Carnil-MRTizanidine and Nimesulide
CitanzTizanidine and Nimesulide
FlectadolTizanidine and Ibuprofen
Meftal-MRTizanidine and Mefenamic Acid
Nimulid-MRTizanidine and Nimesulide
Nimvar-MRTizanidine and Nimesulide
Nizi Tizanidine and Nimesulide
Novolid-MRTizanidine and Nimesulide
Orthobid-MRTizanidine and Nimesulide
Sixer-TIZTizanidine and Diclofenac
Sumo-MRTizanidine and Nimesulide
TizafenTizanidine and Ibuprofen
TizanacTizanidine and Diclofenac
TizuTizanidine and Nimesulide
ZalideTizanidine and Nimesulide
Categories
CAS number51322-75-9
WeightAverage: 253.711
Monoisotopic: 253.018893678
Chemical FormulaC9H8ClN5S
InChI KeyXFYDIVBRZNQMJC-UHFFFAOYSA-N
InChI
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)
IUPAC Name
5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine
SMILES
ClC1=C(NC2=NCCN2)C2=NSN=C2C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzothiadiazoles
SubclassNot Available
Direct parentBenzothiadiazoles
Alternative parentsChlorobenzenes; Aryl Chlorides; Thiadiazoles; Guanidines; Polyamines; Organochlorides
Substituentschlorobenzene; aryl halide; aryl chloride; benzene; thiadiazole; azole; guanidine; polyamine; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzothiadiazoles. These are heterocyclic aromatic compounds containing a benzene ring fused to a thiadiazole ring.
Pharmacology
IndicationFor the management of increased muscle tone associated with spasticity
PharmacodynamicsTizanidine 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.
Mechanism of actionTizanidine reduces spasticity by increasing presynaptic inhibition of motor neurons through agonist action at a2-adrenergic receptor sites.
AbsorptionNot Available
Volume of distribution
  • 2.4 L/kg
Protein binding30%
Metabolism
SubstrateEnzymesProduct
Tizanidine
5-chloro-4-(guanidino)-2,1,3-benzothiadiazoleDetails
Tizanidine
5-chloro-4-(2-imidazolin-4-on-2-ylamino)-2,1,3-benzothiadiazoleDetails
Route of eliminationApproximately 95% of an administered dose is metabolized.
Half life2.5 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.8592
Caco-2 permeable + 0.5323
P-glycoprotein substrate Substrate 0.6545
P-glycoprotein inhibitor I Non-inhibitor 0.8365
P-glycoprotein inhibitor II Non-inhibitor 0.7953
Renal organic cation transporter Inhibitor 0.6577
CYP450 2C9 substrate Non-substrate 0.7953
CYP450 2D6 substrate Non-substrate 0.8018
CYP450 3A4 substrate Non-substrate 0.5795
CYP450 1A2 substrate Non-inhibitor 0.5248
CYP450 2C9 substrate Non-inhibitor 0.7117
CYP450 2D6 substrate Non-inhibitor 0.7867
CYP450 2C19 substrate Non-inhibitor 0.6353
CYP450 3A4 substrate Non-inhibitor 0.781
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5
Ames test Non AMES toxic 0.6538
Carcinogenicity Non-carcinogens 0.8915
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.6573 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6935
hERG inhibition (predictor II) Non-inhibitor 0.8907
Pharmacoeconomics
Manufacturers
  • Acorda therapeutics inc
  • Actavis elizabeth llc
  • Actavis totowa llc
  • Alphapharm party ltd
  • Apotex inc
  • Barr laboratories inc
  • Caraco pharmaceutical laboratories ltd
  • Corepharma llc
  • Dr reddys laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Zanaflex 6 mg capsule4.79USDcapsule
Zanaflex 4 mg capsule3.2USDcapsule
Zanaflex 2 mg capsule2.52USDcapsule
Zanaflex 4 mg tablet2.29USDtablet
Tizanidine hcl 4 mg tablet1.49USDtablet
Zanaflex 2 mg tablet1.42USDtablet
Tizanidine hcl 2 mg tablet1.25USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States64555572001-11-282021-11-28
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP1.4Not Available
Predicted Properties
PropertyValueSource
water solubility1.33e-01 g/lALOGPS
logP1.6ALOGPS
logP2.02ChemAxon
logS-3.3ALOGPS
pKa (strongest basic)7.49ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count2ChemAxon
polar surface area62.2ChemAxon
rotatable bond count1ChemAxon
refractivity64.77ChemAxon
polarizability23.97ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
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.

US20110263863
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07452
PubChem Compound5487
PubChem Substance46505373
ChemSpider5287
BindingDB50240671
Therapeutic Targets DatabaseDAP000234
PharmGKBPA451701
Drug Product Database2259893
RxListhttp://www.rxlist.com/cgi/generic/tizanidine.htm
Drugs.comhttp://www.drugs.com/tizanidine.html
WikipediaTizanidine
ATC CodesM03BX02
AHFS Codes
  • 12:20.00
PDB EntriesNot Available
FDA labelshow(145 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AmiodaroneAmiodarone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
AmlodipineAmlopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
BenazeprilTizanidine increases the risk of hypotension with the ACE inhibitor
CaptoprilTizanidine increases the risk of hypotension with the ACE inhibitor
CilazaprilTizanidine increases the risk of hypotension with the ACE inhibitor
CimetidineCimetidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
CiprofloxacinCiprofloxacin inhibits the metabolism and clearance of Tizanidine. Concomitant therapy is contraindicated.
DiclofenacDiclofenac may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
DonepezilPossible antagonism of action
EnalaprilTizanidine increases the risk of hypotension with the ACE inhibitor
EthanolEthanol increases the adverse effects of Tizanidine. The CNS depressant effects of these agents are additive.
Ethinyl EstradiolEthinyl estradiol may increase the serum concentration of tizanidine. Monitor for changes in the therapeutic and adverse effects of tizanidine if ethinyl estradiol is initiated, discontinued or dose changed.
FluoxetineFluoxetine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
FluvoxamineFluvoxamine inhibits the metabolism and clearance of tizanidine. Concomitant therapy is contraindicated.
FosinoprilTizanidine increases the risk of hypotension with the ACE inhibitor
GalantaminePossible antagonism of action
GemfibrozilGemfibrozil may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
KetoconazoleKetoconazole may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
LidocaineLidocaine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
LisinoprilTizanidine increases the risk of hypotension with the ACE inhibitor
MestranolOral contraceptives decrease the clearance of Tizanidine.
MethoxsalenMethoxsalen may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
MexiletineMexilitene may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
MiconazoleMiconazole may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
MoexiprilTizanidine increases the risk of hypotension with the ACE inhibitor
MoxifloxacinMoxifloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
NifedipineNifedipine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
NorethindroneThe contraceptive increases the effect of tizanidine
NorfloxacinNorfloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
OfloxacinOfloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
PerindoprilTizanidine increases the risk of hypotension with the ACE inhibitor
PrimaquinePrimaquine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
PropafenonePropafenone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
PropofolPropofol may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
QuinaprilTizanidine increases the risk of hypotension with the ACE inhibitor
QuinupristinThis combination presents an increased risk of toxicity
RamiprilTizanidine increases the risk of hypotension with the ACE inhibitor
RivastigminePossible antagonism of action
SpiraprilTizanidine increases the risk of hypotension with the ACE inhibitor
ThiabendazoleThe strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Tizanidine by decreasing Tizanidine metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Tizanidine if Thiabendazole is initiated, discontinued or dose changed.
TiclopidineTiclopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
TrandolaprilTizanidine increases the risk of hypotension with the ACE inhibitor
TranylcypromineTranylcypromine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TrimipramineTrimipramine may reduce the antihypertensive effect of the alpha2-agonist, Tizandine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Tizandine should be withdrawn very gradually to reduce the risk of hypertensive crisis.
TriprolidineThe CNS depressants, Triprolidine and Tizanidine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food InteractionsNot Available

Targets

1. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

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

2. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

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

3. Alpha-2C adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-2C adrenergic receptor P18825 Details

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

4. Nischarin

Kind: protein

Organism: Human

Pharmacological action: no

Actions: agonist

Components

Name UniProt ID Details
Nischarin Q9Y2I1 Details

References:

  1. Rolon PA: Myxoglobulosis of the appendix. Int Surg. 1977 Jun-Jul;62(6-7):355-6. Pubmed

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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. Epub 2009 Nov 24. Pubmed
  4. 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

Comments
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Drug created on June 13, 2005 07:24 / Updated on January 09, 2014 11:38