Details
Stereochemistry | RACEMIC |
Molecular Formula | C9H8ClN5S.C3H6O3 |
Molecular Weight | 343.789 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(O)C(O)=O.ClC1=C(NC2=NCCN2)C3=NSN=C3C=C1
InChI
InChIKey=LIVDAGUZLLMLHS-UHFFFAOYSA-N
InChI=1S/C9H8ClN5S.C3H6O3/c10-5-1-2-6-8(15-16-14-6)7(5)13-9-11-3-4-12-9;1-2(4)3(5)6/h1-2H,3-4H2,(H2,11,12,13);2,4H,1H3,(H,5,6)
DescriptionCurator'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
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095158 |
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Target ID: CHEMBL1942 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15481719 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ZANAFLEX Approved UseTizanidine 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 Date1996 |
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Primary | ZANAFLEX Approved UseTizanidine 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 Date1996 |
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Primary | ZANAFLEX Approved UseTizanidine 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 Date1996 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
13 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3447935 |
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
Dose | Population | Adverse 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%) Sources: Page: p.716Fatigue (3.9%) Muscular weakness (3.9%) Affective disorder (3.9%) Bradycardia (2%) Ventricular extrasystoles (2%) Anxiety (2%) Sleep disturbance (2%) Syncope (2%) |
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 Sources: Page: p.1Liver injury Sedation Hallucinations Renal impairment |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
Title | Date | PubMed |
---|---|---|
Development of a simple spasticity quantification method: effects of tizanidine on spasticity in patients with sequelae of cerebrovascular disease. | 1992 Feb |
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Scopolamine-induced convulsions in food given fasted mice: effects of clonidine and tizanidine. | 1999 Jun |
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Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension. | 2000 Dec |
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An open-label dose-titration study of the efficacy and tolerability of tizanidine hydrochloride tablets in the prophylaxis of chronic daily headache. | 2001 Apr |
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Antagonistic effects of selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery. | 2001 Jan |
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Spasticity: a rehabilitation challenge in the elderly. | 2001 Nov-Dec |
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Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review. | 2002 Aug |
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Low-dose tizanidine with nonsteroidal anti-inflammatory drugs for detoxification from analgesic rebound headache. | 2002 Mar |
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Treatments for spasticity and pain in multiple sclerosis: a systematic review. | 2003 |
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Anti-spasticity agents for multiple sclerosis. | 2003 |
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Eosinophilic exudative pleural effusion after initiation of tizanidine treatment: a case report. | 2003 Mar |
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Tizanidine is not a cure for chronic daily headache. | 2003 Mar |
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High-dose tizanidine abuse. | 2003 Summer |
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Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization. | 2004 Apr |
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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 |
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Preventive migraine therapy: what is new. | 2004 Oct |
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Application of HPLC and HPTLC for the simultaneous determination of tizanidine and rofecoxib in pharmaceutical dosage form. | 2005 Feb 7 |
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Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
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[Therapy of pain syndromes in multiple sclerosis -- an overview with evidence-based recommendations]. | 2005 May |
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[The usefulness of tizanidine. A one-year follow-up of the treatment of spasticity in infantile cerebral palsy]. | 2006 Aug 1-15 |
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Combination of tizanidine and amitriptyline in the prophylaxis of chronic tension-type headache: evaluation of efficacy and impact on quality of life. | 2006 Feb |
|
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1331591
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).
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DTXSID80909981
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106314-85-6
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U2956E1O7Q
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184639
Created by
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SUBSTANCE RECORD