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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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZANAFLEX
Primary
ZANAFLEX
Primary
ZANAFLEX

Cmax

ValueDoseCo-administeredAnalytePopulation
3.1 ng/mL
5 mg single, oral
TIZANIDINE blood
Homo sapiens
11 ng/mL
20 mg single, oral
TIZANIDINE blood
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
13 ng × h/mL
5 mg single, oral
TIZANIDINE blood
Homo sapiens
54 ng × h/mL
20 mg single, oral
TIZANIDINE blood
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2.8 h
5 mg single, oral
TIZANIDINE blood
Homo sapiens
3.2 h
20 mg single, oral
TIZANIDINE blood
Homo sapiens

Doses

AEs

PubMed

Sample Use Guides

In Vivo Use Guide
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
Record UNII
6AI06C00GW
Record Status Validated (UNII)
Record Version