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Details

Stereochemistry ACHIRAL
Molecular Formula C9H8ClN5S.ClH
Molecular Weight 290.172
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIZANIDINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=ZWUKMNZJRDGCTQ-UHFFFAOYSA-N
InChI=1S/C9H8ClN5S.ClH/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);1H

HIDE SMILES / InChI

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

1996
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

1996
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

1996
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
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
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:
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:
unhealthy
Disc. AE: Hypotension, Liver injury...
AEs leading to
discontinuation/dose reduction:
Hypotension
Liver injury
Sedation
Hallucinations
Renal impairment
Sources:
AEs

AEs

AESignificanceDosePopulation
Anxiety 2%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
Bradycardia 2%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
Sleep disturbance 2%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
Syncope 2%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
Ventricular extrasystoles 2%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
Affective disorder 3.9%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
Fatigue 3.9%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
Muscular weakness 3.9%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
Drowsiness 5.9%
Disc. AE
19.36 mg 3 times / day multiple, oral
Recommended
Dose: 19.36 mg, 3 times / day
Route: oral
Route: multiple
Dose: 19.36 mg, 3 times / day
Sources:
unhealthy, 18 - 77
Health Status: unhealthy
Age Group: 18 - 77
Sex: M+F
Sources:
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
PubMed

PubMed

TitleDatePubMed
Rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2: implications for in vitro prediction of drug interactions.
2006-12
[The study and treatment of dystonias in childhood].
2006-10-10
Rofecoxib is a potent inhibitor of cytochrome P450 1A2: studies with tizanidine and caffeine in healthy subjects.
2006-09
[The usefulness of tizanidine. A one-year follow-up of the treatment of spasticity in infantile cerebral palsy].
2006-07-28
Non-antiepileptic drugs for trigeminal neuralgia.
2006-07-19
In-vitro studies of tizanidine controlled-release microcapsular matrices.
2006-07
Tizanidine distribution in a postmortem case.
2006-06
Rifampicin is only a weak inducer of CYP1A2-mediated presystemic and systemic metabolism: studies with tizanidine and caffeine.
2006-06
Mediation of late excitation from human hand muscles via parallel group II spinal and group I transcortical pathways.
2006-04-15
Pharmacological interventions for spasticity following spinal cord injury: results of a Cochrane systematic review.
2006-03
Combination of tizanidine and amitriptyline in the prophylaxis of chronic tension-type headache: evaluation of efficacy and impact on quality of life.
2006-02
Botulinum toxin type A for the treatment of the spastic equinus foot in cerebral palsy.
2006-02
Quantification of tizanidine in human plasma by liquid chromatography coupled to tandem mass spectrometry.
2006
Pharmacologic interventions for reducing spasticity in cerebral palsy.
2005-10
Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2.
2005-10
Involvement of supraspinal imidazoline receptors and descending monoaminergic pathways in tizanidine-induced inhibition of rat spinal reflexes.
2005-09
Assessment of efficacy and psychomotor performances of thiocolchicoside and tizanidine in patients with acute low back pain.
2005-07
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005-06
[Spasticity. Physical therapy, preventive measures and treatment].
2005-06
[Therapy of pain syndromes in multiple sclerosis -- an overview with evidence-based recommendations].
2005-05
[Extreme sinus bradycardia (30/min) with acute right heart failure under tizanidine (Sirdalud). Possible pharmacological interaction with rofecoxib (Vioxx)].
2005-04-15
Botulinum toxin type A for the treatment of the upper limb spasticity after stroke: a meta-analysis.
2005-03
Group II excitations from plantar foot muscles to human leg and thigh motoneurones.
2005-03
Simultaneous LC determination of tizanidine and rofecoxib in tablets.
2005-02-07
Application of HPLC and HPTLC for the simultaneous determination of tizanidine and rofecoxib in pharmaceutical dosage form.
2005-02-07
Involuntary jerking of lower half of the body (spinal myoclonus).
2005-02
Symptomatic bradycardia probably due to tizanidine hydrochloride in a chronic hemodialysis patient.
2005-02
Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism.
2004-12
[Effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia].
2004-11
Drug interaction of tizanidine and fluvoxamine.
2004-11
Hypotension due to interaction between lisinopril and tizanidine.
2004-11
Oral antispastic drugs in nonprogressive neurologic diseases: a systematic review.
2004-10-26
Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs.
2004-10-18
Preventive migraine therapy: what is new.
2004-10
Alpha2-adrenergic receptor subtype specificity of intrathecally administered tizanidine used for analgesia for neuropathic pain.
2004-10
[Progressive encephalomyelitis with rigidity responsive to gabapentin: a pharmacological update].
2004-10
[Pharmacology and upper limb poststroke spasticity: a review. International Society of Prosthetics and Orthotics].
2004-10
Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review.
2004-08
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.
2004-07-05
Tizanidine for the treatment of intention myoclonus: a case series.
2004-07
[Intrathecal baclofen in severe spasticity due to multiple sclerosis].
2004-06-04
Muscle relaxants in the treatment of myofascial face pain. A literature review.
2004-06
Efficacy of tizanidine hydrochloride in the treatment of myofascial face pain.
2004-04
Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization.
2004-04
Retrospective review of Tizanidine (Zanaflex) overdose.
2004
A benefit-risk assessment of baclofen in severe spinal spasticity.
2004
High-dose tizanidine abuse.
2003
Tizanidine is effective in the treatment of myofascial pain syndrome.
2002-10
Alpha(2) receptors and agonists in pain management.
2001-10
Development of a simple spasticity quantification method: effects of tizanidine on spasticity in patients with sequelae of cerebrovascular disease.
1992-02
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).
Name Type Language
ONTRALFY
Preferred Name English
TIZANIDINE HYDROCHLORIDE
MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
TIZANIDINE HCL
Common Name English
DS-103-282
Code English
2,1,3-BENZOTHIADIAZOL-4-AMINE, 5-CHLORO-N-(4,5-DIHYDRO-1H-IMIDAZOL-2-YL)-, MONOHYDROCHLORIDE
Common Name English
AN021
Code English
TIZANIDINE HYDROCHLORIDE [MI]
Common Name English
Tizanidine hydrochloride [WHO-DD]
Common Name English
TIZANIDINE HYDROCHLORIDE [USAN]
Common Name English
DS 103-282
Code English
TIZANIDINE HYDROCHLORIDE [MART.]
Common Name English
TIZANIDINE (AS HYDROCHLORIDE)
Common Name English
TIZANIDINE HYDROCHLORIDE [USP IMPURITY]
Common Name English
TIZANIDINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
5-CHLORO-4-(2-IMIDAZOLIN-2-YLAMINO)-2,1,3-BENZOTHIADIAZOLE MONOHYDROCHLORIDE.
Common Name English
AN-021
Code English
TIZANIDINE HYDROCHLORIDE [JAN]
Common Name English
TIZANIDINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
TIZANIDINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
TIZANIDINE HYDROCHLORIDE [VANDF]
Common Name English
ZANAFLEX
Brand Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 79193
Created by admin on Mon Mar 31 18:10:45 GMT 2025 , Edited by admin on Mon Mar 31 18:10:45 GMT 2025
NCI_THESAURUS C29709
Created by admin on Mon Mar 31 18:10:45 GMT 2025 , Edited by admin on Mon Mar 31 18:10:45 GMT 2025
Code System Code Type Description
RXCUI
236460
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PRIMARY RxNorm
PUBCHEM
114869
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PRIMARY
FDA UNII
B53E3NMY5C
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PRIMARY
EPA CompTox
DTXSID9046990
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PRIMARY
SMS_ID
100000091800
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PRIMARY
ChEMBL
CHEMBL1079
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PRIMARY
EVMPD
SUB04895MIG
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PRIMARY
CAS
64461-82-1
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PRIMARY
NCI_THESAURUS
C47760
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PRIMARY
DRUG BANK
DBSALT000550
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PRIMARY
MERCK INDEX
m10912
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PRIMARY Merck Index
DAILYMED
B53E3NMY5C
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PRIMARY
RS_ITEM_NUM
1667905
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PRIMARY
USAN
GG-4
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PRIMARY