Identification

Name
Tizanidine
Accession Number
DB00697  (APRD00128)
Type
Small Molecule
Groups
Approved, Investigational
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
  • 5-Chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole
  • Tizanidin
  • Tizanidina
  • Tizanidine
  • Tizanidinum
External IDs
AN 021 / DS 103-282
Product Ingredients
IngredientUNIICASInChI Key
Tizanidine HydrochlorideB53E3NMY5C64461-82-1ZWUKMNZJRDGCTQ-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TizanidineTablet2 mgOralAa Pharma IncNot applicableNot applicableCanada
TizanidineTablet4 mgOralAa Pharma Inc2004-11-17Not applicableCanada
Tizanidine HydrochlorideCapsule, gelatin coated4 mg/1OralActavis Pharma Company2012-02-06Not applicableUs00591 2789 86 nlmimage10 903cc836
Tizanidine HydrochlorideCapsule, gelatin coated2 mg/1OralClinical Solutions Wholsesale2012-02-062017-06-21Us58118 278820180913 8702 m9n6id
Tizanidine HydrochlorideCapsule, gelatin coated6 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2012-02-06Not applicableUs
Tizanidine HydrochlorideCapsule, gelatin coated2 mg/1OralActavis Pharma Company2012-02-06Not applicableUs00591 2788 86 nlmimage10 873cc3b6
Tizanidine HydrochlorideCapsule, gelatin coated6 mg/1OralActavis Pharma Company2012-02-06Not applicableUs
Tizanidine HydrochlorideCapsule, gelatin coated6 mg/1Oralbryant ranch prepack2012-02-06Not applicableUs
ZanaflexCapsule4 mg/1OralStat Rx USA2002-08-29Not applicableUs
ZanaflexTablet4 mg/1OralPd Rx Pharmaceuticals, Inc.1997-01-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Comfort Pac with TizanidineKit4 mg/1Pd Rx Pharmaceuticals, Inc.2013-07-09Not applicableUs
Mylan-tizanidineTablet4 mgOralMylan Pharmaceuticals2006-02-162017-01-09Canada
Pal-tizanidineTablet4 mgOralPaladin Labs Inc1999-10-29Not applicableCanada
TizanidineTablet2 mg/1Oralbryant ranch prepack2013-04-01Not applicableUs
TizanidineTablet4 mg/1OralUnichem Pharmaceuticals (USA), Inc.2013-04-01Not applicableUs
TizanidineTablet2 mg/1OralClinical Solutions Wholsesale2002-07-032017-06-26Us58118 017920180913 8702 1ij16o8
TizanidineTablet4 mg/1OralAidarex Pharmaceuticals LLC2002-07-03Not applicableUs
TizanidineTablet2 mg/1OralPreferreed Pharmaceuticals Inc.2014-03-26Not applicableUs
TizanidineTablet2 mg/1OralRemedy Repack2015-12-16Not applicableUs
TizanidineTablet4 mg/1OralProficient Rx LP2002-07-03Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ZanaflexTizanidine Hydrochloride (2 mg/1)TabletOralAcorda Therapeutics, Inc.2008-01-162008-01-16Us
International/Other Brands
Cimbrar (Euroetika) / Musant (Actavis) / Myores (Meprofarm) / Navizan (Caber) / Relaxkov (Blaskov) / Sirdalid (Novartis) / Sirdalud (Novartis) / Sirdalud MR (Novartis) / Sizolan (Dr. Reddy's) / Spaslax (Panion & BF) / Telzanine (Nisshin Seiyaku) / Ternelin (Novartis) / Tizadin (ACL) / Tizaflex (Actavis) / Tizalud (Opsonin) / Tizan (Sun) / Zanpeak (Tatsumi Kagaku) / Zitanid (Novell)
Categories
UNII
6AI06C00GW
CAS number
51322-75-9
Weight
Average: 253.711
Monoisotopic: 253.018893678
Chemical Formula
C9H8ClN5S
InChI Key
XFYDIVBRZNQMJC-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

Pharmacology

Indication

For the management of increased muscle tone associated with spasticity

Associated Conditions
Pharmacodynamics

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.

Mechanism of action

Tizanidine reduces spasticity by increasing presynaptic inhibition of motor neurons through agonist action at a2-adrenergic receptor sites.

TargetActionsOrganism
UAlpha-2A adrenergic receptor
agonist
Human
AAlpha-2B adrenergic receptor
agonist
Human
AAlpha-2C adrenergic receptor
agonist
Human
NNischarin
agonist
Human
Absorption
Not Available
Volume of distribution
  • 2.4 L/kg
Protein binding

30%

Metabolism
Route of elimination

Approximately 95% of an administered dose is metabolized.

Half life

2.5 hours

Clearance
Not Available
Toxicity
Not Available
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 Tizanidine is combined with 7-Nitroindazole.
AbirateroneThe serum concentration of Tizanidine can be increased when it is combined with Abiraterone.
AcebutololThe therapeutic efficacy of Tizanidine can be decreased when used in combination with Acebutolol.
AcepromazineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Aceprometazine.
AcyclovirThe serum concentration of Tizanidine can be increased when it is combined with Acyclovir.
AdipiplonThe risk or severity of adverse effects can be increased when Tizanidine is combined with Adipiplon.
AgomelatineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Agomelatine.
AlaproclateThe risk or severity of adverse effects can be increased when Tizanidine is combined with Alaproclate.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Tizanidine.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0060964
KEGG Compound
C07452
PubChem Compound
5487
PubChem Substance
46505373
ChemSpider
5287
BindingDB
50240671
ChEBI
63629
ChEMBL
CHEMBL1079
Therapeutic Targets Database
DAP000234
PharmGKB
PA451701
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tizanidine
ATC Codes
M03BX02 — Tizanidine
AHFS Codes
  • 12:20.04 — Centrally Acting Skeletal Muscle Relaxants
FDA label
Download (145 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherMalignant Melanoma, Neoplasms1
1CompletedTreatmentHealthy Volunteers2
1TerminatedTreatmentSpasticity Due to Cerebral Palsy1
1, 2CompletedTreatmentMuscle Spasticity1
2CompletedTreatmentSpasticity1
2WithdrawnTreatmentAcute Muscle Pain1
3CompletedTreatmentDisseminated Sclerosis / Muscle Spasticity / Spinal Cord Injuries (SCI) / Strokes1
3CompletedTreatmentLow Back Pain (LBP)1
3CompletedTreatmentVertebrogenic Radiculopathy L5, S11
4CompletedTreatmentThyroidectomy1
4CompletedTreatmentUnilateral Inguinal Hernia1
4CompletedTreatmentUpper Limb Spasticity1
4RecruitingTreatmentLow Back Pain (LBP)1
Not AvailableCompletedNot AvailableAcute Gouty Arthritis / Arthritis / Headaches / Migraines / Muscle Spasms / Radicular syndrome / Synovitis / Tendonitis1

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
  • Acorda Therapeutics
  • Aidarex Pharmacuticals LLC
  • Alphapharm Party Ltd.
  • Altura Pharmaceuticals Inc.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Corepharma LLC
  • Deca Pharmaceuticals LLC
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • Elan Pharmaceuticals Inc.
  • Eon Labs
  • Genpharm LP
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patheon Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Torpharm Inc.
  • UDL Laboratories
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
Kit4 mg/1
TabletOral2 mg
TabletOral2 mg/1
TabletOral4 mg
CapsuleOral2 mg/1
Capsule, gelatin coatedOral2 mg/1
Capsule, gelatin coatedOral6 mg/1
TabletOral4 mg/1
CapsuleOral4 mg/1
CapsuleOral6 mg/1
Capsule, gelatin coatedOral4 mg/1
Prices
Unit descriptionCostUnit
Zanaflex 6 mg capsule4.79USD capsule
Zanaflex 4 mg capsule3.2USD capsule
Zanaflex 2 mg capsule2.52USD capsule
Zanaflex 4 mg tablet2.29USD tablet
Tizanidine hcl 4 mg tablet1.49USD tablet
Zanaflex 2 mg tablet1.42USD tablet
Tizanidine hcl 2 mg tablet1.25USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6455557No2001-11-282021-11-28Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.133 mg/mLALOGPS
logP1.6ALOGPS
logP2.02ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)7.49ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area62.2 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity64.77 m3·mol-1ChemAxon
Polarizability23.97 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8592
Caco-2 permeable+0.5323
P-glycoprotein substrateSubstrate0.6545
P-glycoprotein inhibitor INon-inhibitor0.8365
P-glycoprotein inhibitor IINon-inhibitor0.7953
Renal organic cation transporterInhibitor0.6577
CYP450 2C9 substrateNon-substrate0.7953
CYP450 2D6 substrateNon-substrate0.8018
CYP450 3A4 substrateNon-substrate0.5795
CYP450 1A2 substrateNon-inhibitor0.5248
CYP450 2C9 inhibitorNon-inhibitor0.7117
CYP450 2D6 inhibitorNon-inhibitor0.7867
CYP450 2C19 inhibitorNon-inhibitor0.6353
CYP450 3A4 inhibitorNon-inhibitor0.781
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5
Ames testNon AMES toxic0.6538
CarcinogenicityNon-carcinogens0.8915
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6573 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6935
hERG inhibition (predictor II)Non-inhibitor0.8907
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-5490000000-5ee0610f321160b63c82
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

Taxonomy

Description
This compound 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiadiazoles
Sub Class
Not Available
Direct Parent
Benzothiadiazoles
Alternative Parents
Benzenoids / Aryl chlorides / Thiadiazoles / Imidazolines / Heteroaromatic compounds / Guanidines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
2,1,3-benzothiadiazole / Aryl chloride / Aryl halide / Benzenoid / Azole / Heteroaromatic compound / 2-imidazoline / Thiadiazole / Guanidine / Propargyl-type 1,3-dipolar organic compound
show 10 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
imidazoles, benzothiadiazole (CHEBI:63629)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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 oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
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. [PubMed:8930173]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
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. [PubMed:8930173]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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
Uniprot Name
Alpha-2C adrenergic receptor
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. [PubMed:8930173]
Details
4. Nischarin
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Agonist
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-si...
Gene Name
NISCH
Uniprot ID
Q9Y2I1
Uniprot Name
Nischarin
Molecular Weight
166627.105 Da
References
  1. Rolon PA: Myxoglobulosis of the appendix. Int Surg. 1977 Jun-Jul;62(6-7):355-6. [PubMed:893017]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
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]
  4. Karjalainen MJ, Neuvonen PJ, Backman JT: Rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2: implications for in vitro prediction of drug interactions. Drug Metab Dispos. 2006 Dec;34(12):2091-6. doi: 10.1124/dmd.106.011965. Epub 2006 Sep 19. [PubMed:16985100]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  6. Tizanidine FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on September 23, 2018 19:37