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)
| Molecular Formula | C3H6O3 |
| Molecular Weight | 90.0779 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
| 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 |
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 |
|||
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 |
|||
| 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 |
|||
| 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 Recommended Dose: 19.36 mg, 3 times / day Route: oral Route: multiple Dose: 19.36 mg, 3 times / day Sources: |
unhealthy, 18 - 77 |
Disc. AE: Drowsiness, Fatigue... AEs leading to discontinuation/dose reduction: Drowsiness (5.9%) Sources: Fatigue (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: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Hypotension, Liver injury... AEs leading to discontinuation/dose reduction: Hypotension Sources: Liver injury Sedation Hallucinations Renal impairment |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 Health Status: unhealthy Sources: |
| 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 Health Status: unhealthy Sources: |
| 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 Health Status: unhealthy Sources: |
| 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 Health Status: unhealthy Sources: |
| 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 Health Status: unhealthy Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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
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).
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 21:59:39 GMT 2025
by
admin
on
Mon Mar 31 21:59:39 GMT 2025
|
| Record UNII |
U2956E1O7Q
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Preferred Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
DTXSID80909981
Created by
admin on Mon Mar 31 21:59:39 GMT 2025 , Edited by admin on Mon Mar 31 21:59:39 GMT 2025
|
PRIMARY | |||
|
106314-85-6
Created by
admin on Mon Mar 31 21:59:39 GMT 2025 , Edited by admin on Mon Mar 31 21:59:39 GMT 2025
|
PRIMARY | |||
|
U2956E1O7Q
Created by
admin on Mon Mar 31 21:59:39 GMT 2025 , Edited by admin on Mon Mar 31 21:59:39 GMT 2025
|
PRIMARY | |||
|
184639
Created by
admin on Mon Mar 31 21:59:39 GMT 2025 , Edited by admin on Mon Mar 31 21:59:39 GMT 2025
|
PRIMARY |