Tizanidine
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. This condition may result from the effects of multiple sclerosis, stroke, an acquired brain injury, or a spinal cord injury [7]. It may also be caused by musculoskeletal injury [5]. Regardless of the cause, muscle spasticity can be an extremely painful and debilitating condition. Initially approved by the FDA in 1996, tizanidine is an a2-adrenergic receptor agonist reducing spasticity by the presynaptic inhibition of excitatory neurotransmitters that cause firing of neurons causing spasticity [Label].
- 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 Unlock Additional DataTizanidine Tablet 4 mg Oral Aa Pharma Inc 2004-11-17 Not applicable Canada 
Tizanidine Tablet 2 mg Oral Aa Pharma Inc Not applicable Not applicable Canada 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 
Tizanidine Hydrochloride Capsule, gelatin coated 2 mg/1 Oral Actavis Pharma, Inc. 2012-02-06 Not applicable US 
Tizanidine Hydrochloride Capsule, gelatin coated 2 mg/1 Oral Clinical Solutions Wholsesale 2012-02-06 2017-06-21 US 
Zanaflex Tablet 2 mg/1 Oral Acorda Therapeutics, Inc. 2008-01-16 2008-01-16 US Zanaflex Tablet 4 mg/1 Oral Covis Pharma 2018-08-01 Not applicable US Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Unlock Additional DataComfort 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 Preferred Pharmaceuticals, Inc. 2014-03-05 Not applicable US 
Tizanidine Tablet 2 mg/1 Oral Nucare Pharmaceuticals, Inc. 2004-01-16 Not applicable US Tizanidine Tablet 4 mg/1 Oral Aidarex Pharmaceuticals LLC 2002-07-03 Not applicable US Tizanidine Tablet 4 mg/1 Oral Unichem Pharmaceuticals (USA), Inc. 2013-04-01 Not applicable US Tizanidine Tablet 2 mg/1 Oral Directrx 2014-01-01 Not applicable US Tizanidine Tablet 4 mg/1 Oral Preferreed Pharmaceuticals Inc. 2002-07-03 Not applicable US 
Tizanidine Tablet 4 mg/1 Oral Proficient Rx LP 2003-12-11 Not applicable US Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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- 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
- Agents producing tachycardia
- Agents that produce hypertension
- 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
Tizanidine is indicated for the relief of muscle spasticity, which can interfere with daily activities. The general recommendation is to reserve tizanidine use for periods of time when there is a particular need for relief, as it has a short duration of action [Label, 8].
- Associated Conditions
- Associated Therapies
- Pharmacodynamics
Tizanidine is a rapidly acting drug used for the management of muscle spasticity when it is required. It acts as an agonist at a2-adrenergic receptor sites and relieves symptoms of muscle spasticity, allowing the continuation of daily activities. In animal models, tizanidine has not been shown to exert direct effects on skeletal muscle fibers or the neuromuscular junction, with no significant effect on monosynaptic spinal reflexes. The frequency of muscle spasm and clonus are decreased by tizanidine [7]. This drug has been shown to decrease heart rate and blood pressure in humans [4, 6].
- Mechanism of action
Tizanidine reduces spasticity by causing presynaptic inhibition of motor neurons via agonist actions at a2-adrenergic receptor sites. This drug is centrally acting and leads to a reduction in the release of excitatory amino acids like glutamate and aspartate, which cause neuronal firing that leads to muscle spasm. The above reduction and excitatory neurotransmitter release results in presynaptic inhibition of motor neurons. The strongest effect has been shown to occur on spinal polysynaptic pathways. The anti-nociceptive and anticonvulsant activities of tizanidine may also be attributed to agonist action on alpha-2 receptors. Tizanidine also binds with weaker affinity to the alpha-1 receptors, explaining its slight and temporary effect on the cardiovascular system [7].
Target Actions Organism UAlpha-2 adrenergic receptors agonistHumans NNischarin agonistHumans UAlpha-1 adrenergic receptors agonistHumans - Absorption
This drug undergoes significant first-pass metabolism. After the administration of an oral dose, tizanidine is mostly absorbed. The absolute oral bioavailability of tizanidine is measured to be about 40% [Label].
Effect of food on absorption
Food has been shown to increase absorption for both the tablets and capsules. The increase in absorption with the tablet (about 30%) was noticeably higher than the capsule (~10%). When the capsule and tablet were administered with food, the amount absorbed from the capsule was about 80% of the amount absorbed from the tablet [Label]. It is therefore advisable to take this drug with food for increased absorption, especially in tablet form.
- Volume of distribution
Extensively distributed throughout the body. The average steady-state volume of distribution is 2.4 L/kg [Label].
- Protein binding
About 30% bound to plasma proteins [Label].
- Metabolism
About 95% of the ingested dose of tizanidine is metabolized. The main enzyme involved in the hepatic metabolism of tizanidine is CYP1A2 [Label].
- Route of elimination
This drug is mainly eliminated by the kidney [Label].
- Half life
Approximately 2.5 hours [Label]
- Clearance
A note on renal impairment Tizanidine clearance is found to be decreased by more than 50% in elderly patients with renal insufficiency (creatinine clearance < 25 mL/min) compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. This drug should be used with caution in patients with renal impairment [Label].
- Toxicity
LD50 information
Oral LD50 (rat): 414 mg/kg; Subcutaneous LD50 (rat): 282 mg/kg; Oral LD50 (mouse): 235 mg/kg [MSDS]
Use in pregnancy
Animal studies have determined that this drug causes fetal harm [Label]. Studies have not been performed in humans, and it is advisable to ensure that tizanidine use in pregnant women should be reserved for cases in which possible benefit clearly outweighs the possible risk to mother and unborn child [8].
Use in breastfeeding
In studies of rat models, this tizanidine was found excreted in the breastmilk with a milk-to-blood ratio of 1.8:1 [Label]. In young nursing rats, abnormal results were obtained in tests indicative of central nervous system function. Various developmental changes that may have been attributable to the drug were observed. It is unknown whether tizanidine is excreted in human milk. It is a lipid-soluble drug, however, and likely to be excreted into breast milk [8].
Carcinogenesis and mutagenesis
No signs of carcinogenicity were observed in two dietary studies performed in rodent models. Tizanidine was given to mice for 78 weeks at doses reaching a maximum 16 mg/kg (equivalent to twice the maximum recommended human dose). In addition, the drug was given to rats for 104 weeks at doses reaching 9 mg/kg (equivalent to 2.5 times the maximum recommended human dose). A lack of a statistically significant increase in the occurrence of tumors in either study group [8].
Tizanidine was not found to be mutagenic or clastogenic in several laboratory essays, including the bacterial Ames test, the mammalian gene mutation test, in addition to the chromosomal aberration test in Chinese hamster cells and several other assays [8].
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.
Learn moreStructured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.
Learn moreStructured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.
Learn moreInteractions
- Drug Interactions
Drug Interaction Unlock Additional Data(R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Tizanidine. 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid The risk or severity of hypotension can be increased when Tizanidine is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid. 1-benzylimidazole The risk or severity of hypertension can be increased when Tizanidine is combined with 1-benzylimidazole. 2,5-Dimethoxy-4-ethylamphetamine The risk or severity of hypertension can be increased when Tizanidine is combined with 2,5-Dimethoxy-4-ethylamphetamine. 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 Tizanidine may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy. 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 Tizanidine may increase the excretion rate of 6-O-benzylguanine which could result in a lower serum level and potentially a reduction in efficacy. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionEvidence Level
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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- 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
- Henney HR 3rd, Runyan JD: A clinically relevant review of tizanidine hydrochloride dose relationships to pharmacokinetics, drug safety and effectiveness in healthy subjects and patients. Int J Clin Pract. 2008 Feb;62(2):314-24. doi: 10.1111/j.1742-1241.2007.01660.x. [PubMed:18199279]
- Malanga G, Reiter RD, Garay E: Update on tizanidine for muscle spasticity and emerging indications. Expert Opin Pharmacother. 2008 Aug;9(12):2209-15. doi: 10.1517/14656566.9.12.2209 . [PubMed:18671474]
- Wagstaff AJ, Bryson HM: Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435-52. doi: 10.2165/00003495-199753030-00007. [PubMed:9074844]
- Mathias CJ, Luckitt J, Desai P, Baker H, el Masri W, Frankel HL: Pharmacodynamics and pharmacokinetics of the oral antispastic agent tizanidine in patients with spinal cord injury. J Rehabil Res Dev. 1989 Fall;26(4):9-16. [PubMed:2600869]
- Mense S: Muscle pain: mechanisms and clinical significance. Dtsch Arztebl Int. 2008 Mar;105(12):214-9. doi: 10.3238/artzebl.2008.0214. Epub 2008 Mar 21. [PubMed:19629211]
- Taittonen M, Raty H, Kirvela O, Aantaa R, Kanto J: The metabolic effects of oral tizanidine in healthy volunteers. Acta Anaesthesiol Scand. 1995 Jul;39(5):628-32. [PubMed:7572012]
- Shirin Ghanavatian; Armen Derian (2019). Tizanidine. StatPearls.
- Canadian monograph, Tizanidine [File]
- 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 (329 KB)
- MSDS
- Download (24.2 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 Back Pain Lower Back 1 4 Completed Treatment Thyroidectomy 1 4 Completed Treatment Unilateral Inguinal Hernia 1 4 Completed Treatment Upper Limb Spasticity 1 Not Available Completed Not Available Acute Gouty Arthritis / Arthritis / Headaches / Migraine / 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/1 Tablet Oral 2 mg 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) Unlock Additional DataUS6455557 No 2002-09-24 2021-11-28 US Additional Data Available- Filed On
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 280 https://www.lookchem.com/Tizanidine-hydrochloride/ boiling point (°C) 391.2 https://www.lookchem.com/Tizanidine/ water solubility slightly soluble FDA label logP 1.72 https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1079/ pKa 7.48 https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1079/ - 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 group
- Organism
- Humans
- 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...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-2A adrenergic receptor | P08913 |
| Alpha-2B adrenergic receptor | P18089 |
| Alpha-2C adrenergic receptor | P18825 |
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]
- Giovannitti JA Jr, Thoms SM, Crawford JJ: Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. 2015 Spring;62(1):31-9. doi: 10.2344/0003-3006-62.1.31. [PubMed:25849473]
- Leiphart JW, Dills CV, Levy RM: Alpha2-adrenergic receptor subtype specificity of intrathecally administered tizanidine used for analgesia for neuropathic pain. J Neurosurg. 2004 Oct;101(4):641-7. doi: 10.3171/jns.2004.101.4.0641. [PubMed:15481719]
- Fairbanks CA, Stone LS, Wilcox GL: Pharmacological profiles of alpha 2 adrenergic receptor agonists identified using genetically altered mice and isobolographic analysis. Pharmacol Ther. 2009 Aug;123(2):224-38. doi: 10.1016/j.pharmthera.2009.04.001. Epub 2009 Apr 23. [PubMed:19393691]
- Zanaflex FDA label [File]
- Kind
- Protein
- Organism
- Humans
- 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
- Tanabe M, Hashimoto M, Ono H: Imidazoline I(1) receptor-mediated reduction of muscle rigidity in the reserpine-treated murine model of Parkinson's disease. Eur J Pharmacol. 2008 Jul 28;589(1-3):102-5. doi: 10.1016/j.ejphar.2008.06.013. Epub 2008 Jun 7. [PubMed:18602099]
- Talakoub R, Abbasi S, Maghami E, Zavareh SM: The effect of oral tizanidine on postoperative pain relief after elective laparoscopic cholecystectomy. Adv Biomed Res. 2016 Feb 8;5:19. doi: 10.4103/2277-9175.175905. eCollection 2016. [PubMed:26962521]
- Canadian monograph, Tizanidine [File]
- FDA label, Zanaflex [File]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-1A adrenergic receptor | P35348 |
| Alpha-1B adrenergic receptor | P35368 |
| Alpha-1D adrenergic receptor | P25100 |
References
- Takayanagi I, Konno F, Ishii C, Takemasa T, Yanagida Y, Shimizu M, Mori H, Sugane H: Actions of tizanidine on alpha 1-and alpha 2-adrenoceptors in the peripheral tissues. Gen Pharmacol. 1984;15(3):239-41. [PubMed:6329897]
- Takayanagi I, Harada M, Koike K, Satoh M: Differences in alpha 1-adrenoceptor mechanisms for phenylephrine and tizanidine in rabbit thoracic aorta and common iliac artery. Can J Physiol Pharmacol. 1991 Dec;69(12):1819-24. [PubMed:1666331]
- Shirin Ghanavatian; Armen Derian (2019). Tizanidine. StatPearls.
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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 April 24, 2019 12:02