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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- 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
Structure for Tizanidine (DB00697)
- 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
Ingredient UNII CAS InChI Key Tizanidine Hydrochloride B53E3NMY5C 64461-82-1 ZWUKMNZJRDGCTQ-UHFFFAOYSA-N - Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Tizanidine Tablet 2 mg Oral Aa Pharma Inc Not applicable Not applicable Canada 
Tizanidine Tablet 4 mg Oral Aa Pharma Inc 2004-11-17 Not applicable Canada Tizanidine Hydrochloride Capsule, gelatin coated 2 mg/1 Oral Clinical Solutions Wholsesale 2012-02-06 2017-06-21 US 
Tizanidine Hydrochloride Capsule, gelatin coated 2 mg/1 Oral Actavis Pharma, Inc. 2012-02-06 Not applicable US 
Tizanidine Hydrochloride Capsule, gelatin coated 6 mg/1 Oral Lake Erie Medical Dba Quality Care Produts Llc 2012-02-06 Not applicable US Tizanidine Hydrochloride Capsule, gelatin coated 6 mg/1 Oral Actavis Pharma, Inc. 2012-02-06 Not applicable US Tizanidine Hydrochloride Capsule, gelatin coated 6 mg/1 Oral bryant ranch prepack 2012-02-06 Not applicable US Tizanidine Hydrochloride Capsule, gelatin coated 4 mg/1 Oral Actavis Pharma, Inc. 2012-02-06 Not applicable US 
Zanaflex Capsule 6 mg/1 Oral Covis Pharma 2018-08-01 Not applicable US Zanaflex Capsule 4 mg/1 Oral Stat Rx USA 2002-08-29 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Comfort Pac with Tizanidine Kit 4 mg/1 Pd Rx Pharmaceuticals, Inc. 2013-07-09 Not applicable US Mylan-tizanidine Tablet 4 mg Oral Mylan Pharmaceuticals 2006-02-16 2017-01-09 Canada Pal-tizanidine Tablet 4 mg Oral Paladin Labs Inc 1999-10-29 Not applicable Canada Tizanidine Tablet 4 mg/1 Oral Aidarex Pharmaceuticals LLC 2002-07-03 Not applicable US Tizanidine Tablet 4 mg/1 Oral Golden State Medical Supply, Inc. 2013-01-08 Not applicable US Tizanidine Tablet 2 mg/1 Oral bryant ranch prepack 2002-07-03 Not applicable US 
Tizanidine Tablet 4 mg/1 Oral bryant ranch prepack 2004-01-16 Not applicable US Tizanidine Tablet 4 mg/1 Oral Proficient Rx LP 2002-07-03 Not applicable US Tizanidine Tablet 2 mg/1 Oral A-S Medication Solutions 2004-01-16 Not applicable US Tizanidine Capsule 6 mg/1 Oral Sa3, Llc 2018-10-01 Not applicable US - 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
- Adrenergic Agents
- Adrenergic Agonists
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Analgesics
- Anticonvulsants
- Autonomic Agents
- Bradycardia-Causing Agents
- Central alpha-2 Adrenergic Agonist
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Substrates
- Hypotensive Agents
- Imidazoles
- Imidazolines
- Muscle Relaxants
- Muscle Relaxants, Centrally Acting Agents
- Musculo-Skeletal System
- Neuromuscular Agents
- Neurotransmitter Agents
- Parasympatholytics
- Peripheral Nervous System Agents
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Sensory System Agents
- 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.
Target Actions Organism UAlpha-2A adrenergic receptor agonistHuman AAlpha-2B adrenergic receptor agonistHuman AAlpha-2C adrenergic receptor agonistHuman NNischarin agonistHuman - 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
Drug Interaction (R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Tizanidine. 2,5-Dimethoxy-4-ethylthioamphetamine The risk or severity of adverse effects can be increased when Tizanidine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine. 3-isobutyl-1-methyl-7H-xanthine The serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Tizanidine. 3,4-Methylenedioxyamphetamine The risk or severity of adverse effects can be increased when Tizanidine is combined with 3,4-Methylenedioxyamphetamine. 4-Bromo-2,5-dimethoxyamphetamine The risk or severity of adverse effects can be increased when Tizanidine is combined with 4-Bromo-2,5-dimethoxyamphetamine. 4-Methoxyamphetamine The risk or severity of adverse effects can be increased when Tizanidine is combined with 4-Methoxyamphetamine. 5-methoxy-N,N-dimethyltryptamine The risk or severity of adverse effects can be increased when Tizanidine is combined with 5-methoxy-N,N-dimethyltryptamine. 6-O-benzylguanine The serum concentration of 6-O-benzylguanine can be increased when it is combined with Tizanidine. 7-Deazaguanine The serum concentration of 7-Deazaguanine can be increased when it is combined with Tizanidine. 7-Nitroindazole The risk or severity of adverse effects can be increased when Tizanidine is combined with 7-Nitroindazole. - 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
Phase Status Purpose Conditions Count 1 Completed Other Malignant Melanoma, Neoplasms 1 1 Completed Treatment Healthy Volunteers 2 1 Terminated Treatment Spasticity Due to Cerebral Palsy 1 1, 2 Completed Treatment Muscle Spasticity 1 2 Completed Treatment Spasticity 1 2 Withdrawn Treatment Acute Muscle Pain 1 3 Completed Treatment Back Pain Lower Back 1 3 Completed Treatment Disseminated Sclerosis / Muscle Spasticity / Spinal Cord Injuries (SCI) / Strokes 1 3 Completed Treatment Vertebrogenic Radiculopathy L5, S1 1 4 Completed Treatment Thyroidectomy 1 4 Completed Treatment Unilateral Inguinal Hernia 1 4 Completed Treatment Upper Limb Spasticity 1 4 Recruiting Treatment Back Pain Lower Back 1 Not Available Completed Not Available Acute Gouty Arthritis / Arthritis / Headaches / Migraines / Muscle Spasms / Radicular syndrome / Synovitis / Tendonitis 1
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
Form Route Strength Kit 4 mg/1 Tablet Oral 2 mg Tablet Oral 2 mg/1 Tablet Oral 4 mg Capsule Oral 2 mg/1 Capsule, gelatin coated Oral 2 mg/1 Capsule, gelatin coated Oral 6 mg/1 Tablet Oral 4 mg/1 Capsule Oral 4 mg/1 Capsule Oral 6 mg/1 Capsule, gelatin coated Oral 4 mg/1 - Prices
Unit description Cost Unit Zanaflex 6 mg capsule 4.79USD capsule Zanaflex 4 mg capsule 3.2USD capsule Zanaflex 2 mg capsule 2.52USD capsule Zanaflex 4 mg tablet 2.29USD tablet Tizanidine hcl 4 mg tablet 1.49USD tablet Zanaflex 2 mg tablet 1.42USD tablet Tizanidine hcl 2 mg tablet 1.25USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) US6455557 No 2001-11-28 2021-11-28 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 1.4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.133 mg/mL ALOGPS logP 1.6 ALOGPS logP 2.02 ChemAxon logS -3.3 ALOGPS pKa (Strongest Basic) 7.49 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 62.2 Å2 ChemAxon Rotatable Bond Count 1 ChemAxon Refractivity 64.77 m3·mol-1 ChemAxon Polarizability 23.97 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - 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 inhibitor Non-inhibitor 0.7117 CYP450 2D6 inhibitor Non-inhibitor 0.7867 CYP450 2C19 inhibitor Non-inhibitor 0.6353 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Mass Spectrum (Electron Ionization) MS splash10-0udi-5490000000-5ee0610f321160b63c82 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not 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
- 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
- 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
- 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
- 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
- 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
- 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]
- 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]
- 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]
- 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]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Tizanidine FDA label [File]
Drug created on June 13, 2005 07:24 / Updated on November 13, 2018 07:51