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Details

Stereochemistry ACHIRAL
Molecular Formula 2C9H8ClN5S.C4H6O4.3H2O
Molecular Weight 679.557
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIZANIDINE HEMISUCCINATE SESQUIHYDRATE

SMILES

O.O.O.OC(=O)CCC(O)=O.ClC1=C(NC2=NCCN2)C3=NSN=C3C=C1.ClC4=C(NC5=NCCN5)C6=NSN=C6C=C4

InChI

InChIKey=QIDIKQBIRYTZGF-UHFFFAOYSA-N
InChI=1S/2C9H8ClN5S.C4H6O4.3H2O/c2*10-5-1-2-6-8(15-16-14-6)7(5)13-9-11-3-4-12-9;5-3(6)1-2-4(7)8;;;/h2*1-2H,3-4H2,(H2,11,12,13);1-2H2,(H,5,6)(H,7,8);3*1H2

HIDE SMILES / InChI

Molecular Formula C4H6O4
Molecular Weight 118.088
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

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 (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
Tizanidine is effective in the treatment of myofascial pain syndrome.
2002 Oct
[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
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
[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
[Extreme sinus bradycardia (30/min) with acute right heart failure under tizanidine (Sirdalud). Possible pharmacological interaction with rofecoxib (Vioxx)].
2005 Apr 15
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
Assessment of efficacy and psychomotor performances of thiocolchicoside and tizanidine in patients with acute low back pain.
2005 Jul
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
[Spasticity. Physical therapy, preventive measures and treatment].
2005 Jun
Botulinum toxin type A for the treatment of the upper limb spasticity after stroke: a meta-analysis.
2005 Mar
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
Pharmacologic interventions for reducing spasticity in cerebral palsy.
2005 Oct
Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2.
2005 Oct
Involvement of supraspinal imidazoline receptors and descending monoaminergic pathways in tizanidine-induced inhibition of rat spinal reflexes.
2005 Sep
Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs.
2005 Sep-Oct
Quantification of tizanidine in human plasma by liquid chromatography coupled to tandem mass spectrometry.
2006
Mediation of late excitation from human hand muscles via parallel group II spinal and group I transcortical pathways.
2006 Apr 15
[The usefulness of tizanidine. A one-year follow-up of the treatment of spasticity in infantile cerebral palsy].
2006 Aug 1-15
Rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2: implications for in vitro prediction of drug interactions.
2006 Dec
Combination of tizanidine and amitriptyline in the prophylaxis of chronic tension-type headache: evaluation of efficacy and impact on quality of life.
2006 Feb
Botulinum toxin type A for the treatment of the spastic equinus foot in cerebral palsy.
2006 Feb
In-vitro studies of tizanidine controlled-release microcapsular matrices.
2006 Jul
Non-antiepileptic drugs for trigeminal neuralgia.
2006 Jul 19
Tizanidine distribution in a postmortem case.
2006 Jun
Rifampicin is only a weak inducer of CYP1A2-mediated presystemic and systemic metabolism: studies with tizanidine and caffeine.
2006 Jun
Pharmacological interventions for spasticity following spinal cord injury: results of a Cochrane systematic review.
2006 Mar
[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 Sat Dec 16 14:48:08 GMT 2023
Edited
by admin
on Sat Dec 16 14:48:08 GMT 2023
Record UNII
LBA0HD4UHF
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TIZANIDINE HEMISUCCINATE SESQUIHYDRATE
Common Name English
BUTANEDIOIC ACID, COMPD. WITH 5-CHLORO-N-(4,5-DIHYDRO-1H-IMIDAZOL-2-YL)-2,1,3-BENZOTHIADIAZOL-4-AMINE, HYDRATE (1:2:3)
Systematic Name English
Code System Code Type Description
PUBCHEM
138455009
Created by admin on Sat Dec 16 14:48:08 GMT 2023 , Edited by admin on Sat Dec 16 14:48:08 GMT 2023
PRIMARY
FDA UNII
LBA0HD4UHF
Created by admin on Sat Dec 16 14:48:08 GMT 2023 , Edited by admin on Sat Dec 16 14:48:08 GMT 2023
PRIMARY
CAS
1051886-74-8
Created by admin on Sat Dec 16 14:48:08 GMT 2023 , Edited by admin on Sat Dec 16 14:48:08 GMT 2023
PRIMARY
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