Identification

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Name
Tizanidine
Accession Number
DB00697  (APRD00128)
Type
Small Molecule
Groups
Approved, Investigational
Description

Tizanidine is a fast-acting drug used for the management of muscle spasm, which may result from the effects of multiple sclerosis, stroke, an acquired brain injury, or a spinal cord injury 9. 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 Alpha-2 adrenergic receptor agonist reducing spasticity by the presynaptic inhibition of excitatory neurotransmitters that cause firing of neurons promoting muscle spasm Label.

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
TizanidineTablet4 mgOralAa Pharma Inc2004-11-17Not applicableCanada
TizanidineTablet2 mgOralAa Pharma IncNot applicableNot applicableCanada
Tizanidine HydrochlorideCapsule, gelatin coated2 mg/1OralClinical Solutions Wholsesale2012-02-062017-06-21Us58118 278820180913 8702 m9n6id
Tizanidine HydrochlorideCapsule, gelatin coated4 mg/1OralActavis Pharma, Inc.2012-02-06Not applicableUs00591 2789 86 nlmimage10 903cc836
Tizanidine HydrochlorideCapsule, gelatin coated6 mg/1Oralbryant ranch prepack2012-02-06Not applicableUs
Tizanidine HydrochlorideCapsule, gelatin coated2 mg/1OralActavis Pharma, Inc.2012-02-06Not applicableUs00591 2788 86 nlmimage10 873cc3b6
Tizanidine HydrochlorideCapsule, gelatin coated6 mg/1OralLake Erie Medical DBA Quality Care Products LLC2012-02-06Not applicableUs
Tizanidine HydrochlorideCapsule, gelatin coated6 mg/1OralActavis Pharma, Inc.2012-02-06Not applicableUs
ZanaflexCapsule4 mg/1OralStat Rx USA2002-08-29Not applicableUs
ZanaflexCapsule2 mg/1OralCovis Pharma2018-08-01Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Comfort Pac with TizanidineKit4 mg/1TopicalPd Rx Pharmaceuticals, Inc.2013-07-09Not applicableUs
Mylan-tizanidineTabletOralMylan Pharmaceuticals2006-02-162017-01-09Canada
Pal-tizanidineTabletOralPaladin Labs Inc1999-10-29Not applicableCanada
TizandineTablet2 mg/1OralDirect_Rx2019-08-19Not applicableUs
TizanidineTablet4 mg/1Oralbryant ranch prepack2013-04-01Not applicableUs
TizanidineTablet4 mg/1Oralbryant ranch prepack2003-12-11Not applicableUs
TizanidineTablet4 mg/1OralDirect_Rx2019-08-13Not applicableUs60505 0252 03 nlmimage10 52382911
TizanidineTablet2 mg/1OralBlenheim Pharmacal, Inc.2014-04-08Not applicableUs
TizanidineTablet2 mg/1Oralbryant ranch prepack2002-07-03Not applicableUs63629 320920180907 15195 1jsko8u
TizanidineTablet2 mg/1OralAidarex Pharmaceuticals LLC2017-11-28Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product 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
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,11.

Associated Conditions
Associated Therapies
Pharmacodynamics

A note on spasticity

Spasticity is an increase in muscle accompanied by uncontrolled, repetitive contractions of skeletal muscles which are involuntary. The patient suffering from muscle spasticity may have reduced mobility and high levels of pain, contributing to poor quality of life and problems performing activities of personal hygiene and care 7.

General effects

Tizanidine is a rapidly acting drug used for the relief of muscle spasticity when it is required for performing specific activities. It acts as an agonist at Alpha-2 adrenergic receptor sites and relieves symptoms of muscle spasticity, allowing the continuation of normal daily activities. In animal models, tizanidine has not been shown to exert direct effects on skeletal muscle fibers or the neuromuscular junction, and has shown no significant effect on monosynaptic spinal reflexes (consisting of the communication between only 1 sensory neuron and 1 motor neuron) 10. The frequency of muscle spasm and clonus are shown to be decreased by tizanidine 9. Tizanidine shows a stronger action on polysynaptic reflexes, which involve several interneurons (relay neurons) communicating with motor neurons stimulating muscle movement 10.

Effects on blood pressure and heart rate

This drug decreases heart rate and blood pressure in humans 4,6. Despite this, rebound hypertension and tachycardia along with increased spasticity can occur when tizanidine is abruptly discontinued 8.

Mechanism of action

Tizanidine reduces spasticity by causing presynaptic inhibition of motor neurons via agonist actions at Alpha-2 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 of tizanidine 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 9.

TargetActionsOrganism
UAlpha-2 adrenergic receptors
agonist
Humans
NNischarin
agonist
Humans
UAlpha-1 adrenergic receptors
agonist
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured 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.

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Additional Data Available
Blackbox Warnings

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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 11.

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 11.

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). There was a lack of a statistically significant increase in the occurrence of tumors in either study group 11.

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 11.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Tizanidine.
1-benzylimidazoleThe therapeutic efficacy of Tizanidine can be decreased when used in combination with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of Tachycardia can be increased when Tizanidine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Tizanidine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineTizanidine 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-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Tizanidine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Tizanidine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Tizanidine is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineTizanidine may increase the excretion rate of 6-O-benzylguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-DeazaguanineTizanidine may increase the excretion rate of 7-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. Chang E, Ghosh N, Yanni D, Lee S, Alexandru D, Mozaffar T: A Review of Spasticity Treatments: Pharmacological and Interventional Approaches. Crit Rev Phys Rehabil Med. 2013;25(1-2):11-22. doi: 10.1615/CritRevPhysRehabilMed.2013007945. [PubMed:25750484]
  8. Suarez-Lledo A, Padulles A, Lozano T, Cobo-Sacristan S, Colls M, Jodar R: Management of Tizanidine Withdrawal Syndrome: A Case Report. Clin Med Insights Case Rep. 2018 Feb 13;11:1179547618758022. doi: 10.1177/1179547618758022. eCollection 2018. [PubMed:29467587]
  9. Shirin Ghanavatian; Armen Derian (2019). Tizanidine. StatPearls.
  10. Reflexes: Components of a Reflex Arc [Link]
  11. 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
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceSubstance, Addiction1
1CompletedOtherMalignant Melanoma, Neoplasms1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentTraumatic Brain Injury (TBI)1
1TerminatedTreatmentSpasticity Due to Cerebral Palsy1
1, 2CompletedTreatmentMuscle Spasticity1
1, 2TerminatedTreatmentDisseminated Sclerosis / Spasticity1
2CompletedTreatmentSpasticity1
2WithdrawnTreatmentAcute Muscle Pain1
3CompletedTreatmentBack Pain Lower Back1
3CompletedTreatmentDisseminated Sclerosis / Muscle Spasticity / Spinal Cord Injuries (SCI) / Strokes1
3CompletedTreatmentVertebrogenic Radiculopathy L5, S11
4CompletedTreatmentBack Pain Lower Back1
4CompletedTreatmentThyroidectomy1
4CompletedTreatmentUnilateral Inguinal Hernia1
4CompletedTreatmentUpper Limb Spasticity1
Not AvailableCompletedNot AvailableAcute Gouty Arthritis / Arthritis / Headaches / Migraine / 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
KitTopical4 mg/1
TabletOral
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)
US6455557No2002-09-242021-11-28Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)280https://www.lookchem.com/Tizanidine-hydrochloride/
boiling point (°C)391.2https://www.lookchem.com/Tizanidine/
water solubilityslightly solubleFDA label
logP1.72https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1079/
pKa7.48https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1079/
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 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:
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]
  2. 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]
  3. 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]
  4. 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]
  5. Zanaflex FDA label [File]
Details
2. Nischarin
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
  1. 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]
  2. 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]
  3. Canadian monograph, Tizanidine [File]
  4. 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:
References
  1. 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]
  2. 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]
  3. 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
  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. 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]
  3. 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]
  4. Flockhart Table of Drug Interactions [Link]
  5. Tizanidine FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on September 15, 2019 08:03