U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C9H8ClN5S
Molecular Weight 253.711
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIZANIDINE

SMILES

ClC1=C(NC2=NCCN2)C3=NSN=C3C=C1

InChI

InChIKey=XFYDIVBRZNQMJC-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C9H8ClN5S
Molecular Weight 253.711
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00697 | https://www.drugs.com/tizanidine.html | http://reference.medscape.com/drug/zanaflex-tizanidine-343071

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. Side effects include dizziness, drowsiness, weakness, nervousness, hallucinations, depression, vomiting, dry mouth, constipation, diarrhea, stomach pain, heartburn, increased muscle spasms, back pain, rash, sweating, and a tingling sensation in the arms, legs, hands, and feet.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZANAFLEX

Approved Use

Tizanidine is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration (2.1)

Launch Date

8.4905283E11
Primary
ZANAFLEX

Approved Use

Tizanidine is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration (2.1)

Launch Date

8.4905283E11
Primary
ZANAFLEX

Approved Use

Tizanidine is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration (2.1)

Launch Date

8.4905283E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.1 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIZANIDINE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
11 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIZANIDINE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
13 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIZANIDINE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
54 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIZANIDINE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.8 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIZANIDINE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3.2 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIZANIDINE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Disc. AE: Drowsiness, Fatigue...
AEs leading to
discontinuation/dose reduction:
Drowsiness (5.9%)
Fatigue (3.9%)
Muscular weakness (3.9%)
Affective disorder (3.9%)
Bradycardia (2%)
Ventricular extrasystoles (2%)
Anxiety (2%)
Sleep disturbance (2%)
Syncope (2%)
Sources: Page: p.716
12 mg 3 times / day multiple, oral
Recommended
Dose: 12 mg, 3 times / day
Route: oral
Route: multiple
Dose: 12 mg, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Spasticity
Sources: Page: p.1
Disc. AE: Hypotension, Liver injury...
AEs leading to
discontinuation/dose reduction:
Hypotension
Liver injury
Sedation
Hallucinations
Renal impairment
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Anxiety 2%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Bradycardia 2%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Sleep disturbance 2%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Syncope 2%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Ventricular extrasystoles 2%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Affective disorder 3.9%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Fatigue 3.9%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Muscular weakness 3.9%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Drowsiness 5.9%
Disc. AE
19.36 mg 3 times / day multiple, oral (mean)
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources: Page: p.716
unhealthy, 18 - 77
n = 51
Health Status: unhealthy
Condition: Spasticity
Age Group: 18 - 77
Sex: M+F
Population Size: 51
Sources: Page: p.716
Hallucinations Disc. AE
12 mg 3 times / day multiple, oral
Recommended
Dose: 12 mg, 3 times / day
Route: oral
Route: multiple
Dose: 12 mg, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Spasticity
Sources: Page: p.1
Hypotension Disc. AE
12 mg 3 times / day multiple, oral
Recommended
Dose: 12 mg, 3 times / day
Route: oral
Route: multiple
Dose: 12 mg, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Spasticity
Sources: Page: p.1
Liver injury Disc. AE
12 mg 3 times / day multiple, oral
Recommended
Dose: 12 mg, 3 times / day
Route: oral
Route: multiple
Dose: 12 mg, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Spasticity
Sources: Page: p.1
Renal impairment Disc. AE
12 mg 3 times / day multiple, oral
Recommended
Dose: 12 mg, 3 times / day
Route: oral
Route: multiple
Dose: 12 mg, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Spasticity
Sources: Page: p.1
Sedation Disc. AE
12 mg 3 times / day multiple, oral
Recommended
Dose: 12 mg, 3 times / day
Route: oral
Route: multiple
Dose: 12 mg, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Spasticity
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
Development of a simple spasticity quantification method: effects of tizanidine on spasticity in patients with sequelae of cerebrovascular disease.
1992 Feb
Alpha(2) receptors and agonists in pain management.
2001 Oct
Cost-effectiveness comparison of tizanidine and baclofen in the management of spasticity.
2002
Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine.
2002 Jun 12
Modulation of NSAID-induced antinociceptive and anti-inflammatory effects by alpha2-adrenoceptor agonists with gastroprotective effects.
2002 May 3
Tizanidine is effective in the treatment of myofascial pain syndrome.
2002 Oct
Protective effects of dextromethorphan and tizanidine on ouabain-induced arrhythmias.
2002 Sep
Chronic headache: New advances in treatment strategies.
2002 Sep 10
[Spastic syndrome and main directions of its treatment].
2003
Preventative treatment for migraine and tension-type headaches : do drugs having effects on muscle spasm and tone have a role?
2003
[Intrathecal baclofen in the treatment of severe spastic tetraplegia and dystonia in children and adolescents].
2003 Apr 21
Anti-spasticity medications.
2003 Jan
Modulatory effects of alpha1-,alpha2-, and beta -receptor agonists on feline spinal interneurons with monosynaptic input from group I muscle afferents.
2003 Jan 1
Antihyperalgesic and side effects of intrathecal clonidine and tizanidine in a rat model of neuropathic pain.
2003 Jun
Eosinophilic exudative pleural effusion after initiation of tizanidine treatment: a case report.
2003 Mar
Tizanidine is not a cure for chronic daily headache.
2003 Mar
[Medical treatment of spasticity].
2003 May
[Intrathecal baclofen in severe spasticity due to multiple sclerosis].
2003 Sep-Oct
High-dose tizanidine abuse.
2003 Summer
Retrospective review of Tizanidine (Zanaflex) overdose.
2004
A benefit-risk assessment of baclofen in severe spinal spasticity.
2004
Efficacy of tizanidine hydrochloride in the treatment of myofascial face pain.
2004 Apr
Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization.
2004 Apr
Paraneoplastic "stiff person syndrome" with metastatic adenocarcinoma and anti-Ri antibodies.
2004 Apr 27
Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review.
2004 Aug
Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism.
2004 Dec
Tizanidine for the treatment of intention myoclonus: a case series.
2004 Jul
Validated semiquantitative/quantitative screening of 51 drugs in whole blood as silylated derivatives by gas chromatography-selected ion monitoring mass spectrometry and gas chromatography electron capture detection.
2004 Jul 5
Muscle relaxants in the treatment of myofascial face pain. A literature review.
2004 Jun
Prophylactic migraine therapy: emerging treatment options.
2004 Jun
[Effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia].
2004 Nov
Drug interaction of tizanidine and fluvoxamine.
2004 Nov
Hypotension due to interaction between lisinopril and tizanidine.
2004 Nov
Preventive migraine therapy: what is new.
2004 Oct
Alpha2-adrenergic receptor subtype specificity of intrathecally administered tizanidine used for analgesia for neuropathic pain.
2004 Oct
[Progressive encephalomyelitis with rigidity responsive to gabapentin: a pharmacological update].
2004 Oct
[Pharmacology and upper limb poststroke spasticity: a review. International Society of Prosthetics and Orthotics].
2004 Oct
Oral antispastic drugs in nonprogressive neurologic diseases: a systematic review.
2004 Oct 26
Involuntary jerking of lower half of the body (spinal myoclonus).
2005 Feb
Symptomatic bradycardia probably due to tizanidine hydrochloride in a chronic hemodialysis patient.
2005 Feb
Simultaneous LC determination of tizanidine and rofecoxib in tablets.
2005 Feb 7
Application of HPLC and HPTLC for the simultaneous determination of tizanidine and rofecoxib in pharmaceutical dosage form.
2005 Feb 7
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Group II excitations from plantar foot muscles to human leg and thigh motoneurones.
2005 Mar
[Therapy of pain syndromes in multiple sclerosis -- an overview with evidence-based recommendations].
2005 May
Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs.
2005 Sep-Oct
Rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2: implications for in vitro prediction of drug interactions.
2006 Dec
In-vitro studies of tizanidine controlled-release microcapsular matrices.
2006 Jul
[The study and treatment of dystonias in childhood].
2006 Oct 10
Rofecoxib is a potent inhibitor of cytochrome P450 1A2: studies with tizanidine and caffeine in healthy subjects.
2006 Sep
Patents

Sample Use Guides

Recommended starting dose: 2 mg; dose can be repeated at 6 to 8 hour intervals, up to a maximum of 3 doses in 24 hours Dosage can be increased by 2 mg to 4 mg per dose, with 1 to 4 days between increases; total daily dose should not exceed 36 mg Tizanidine pharmacokinetics differs between tablets and capsules, and when taken with or without food. These differences could result in a change in tolerability and control of symptoms To discontinue Zanaflex, decrease dose slowly to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia
Route of Administration: Oral
In Vitro Use Guide
Male Wi star rats (300-350g) were decapitated and the kidneys were rapidly removed. The kidneys were minced in ice-cold 50 mM Tris-HCI, 5 mM EDTA (pH 7.7) and then homogenized by a polytron. The homogenate was filtered through 4 layers of silk gauze. and centrifuged at 40,000 X g for 13 min. The pellet was resuspended in 50 mM Tris-HCI, 25 mM NaCI buffer (pH 7.7), incubated for 30 min at 25°C, and recen trifuged as described above. The final pellet was resuspended in 50 mM Tris-HC1 buffer (pH 7.7) and used for the binding assay. Incubations were performed in duplicate at 25°C for 40 min in a total volume of 1 ml. The incubate consisted of 3H p-aminoclonidine (3H-PAC), a suspension of kidney membranes (approximately 0.55 mg/ml) and either buffer alone or buffer containing Tizanidine. Non-specific binding was defined by parallel incubations containing 10,uM phentolamine. In experiments using adrenaline, all samples contained ascortic acid in a final concentration of 0.01%. Incubations were terminated by vacuum filtration over Whatman GF/C filters by using a cell harvester. The filters were washed with ice-cold Tris-HCI; then the filter-bound radioactivity was determined using a scintillation counter (Aloka, Japan).
Substance Class Chemical
Created
by admin
on Wed Jul 05 22:48:29 UTC 2023
Edited
by admin
on Wed Jul 05 22:48:29 UTC 2023
Record UNII
6AI06C00GW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TIZANIDINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
tizanidine [INN]
Common Name English
TIZANIDINE [VANDF]
Common Name English
SIRDALUD
Brand Name English
TIZANIDINE [MI]
Common Name English
Tizanidine [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-ATC M03BX02
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
WHO-VATC QM03BX02
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
NCI_THESAURUS C29709
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
LIVERTOX NBK548048
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
NDF-RT N0000175554
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
NDF-RT N0000009918
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
Code System Code Type Description
SMS_ID
100000082123
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
DRUG CENTRAL
2683
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
MESH
C023754
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
ChEMBL
CHEMBL1079
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
CHEBI
63629
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
PUBCHEM
5487
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
DAILYMED
6AI06C00GW
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
RXCUI
57258
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY RxNorm
MERCK INDEX
M10912
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY Merck Index
IUPHAR
7308
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
CAS
51322-75-9
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
EVMPD
SUB11129MIG
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
WIKIPEDIA
TIZANIDINE
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
FDA UNII
6AI06C00GW
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
EPA CompTox
DTXSID9023679
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
INN
4697
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
NCI_THESAURUS
C61976
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
DRUG BANK
DB00697
Created by admin on Wed Jul 05 22:48:29 UTC 2023 , Edited by admin on Wed Jul 05 22:48:29 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
IN MICROSOMES
TARGET -> AGONIST
SHORT-ACTING
SALT/SOLVATE -> PARENT
EXCRETED UNCHANGED
URINE
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METABOLITE -> PARENT
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MINOR
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METABOLITE INACTIVE -> PARENT
MAJOR
PLASMA; URINE
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PLASMA; URINE
METABOLITE -> PARENT
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ACTIVE MOIETY