Tizanidine

Bezeichnung:Tizanidine

CAS-Nr51322-75-9

Englisch Name:Tizanidine

CBNumberCB9670538

SummenformelC9H8ClN5S

Molgewicht253.71

MOL-Datei51322-75-9.mol

Tizanidine physikalisch-chemischer Eigenschaften

Schmelzpunkt	221-223°
Siedepunkt	391.2±52.0 °C(Predicted)
Dichte	1.82±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
Löslichkeit	H₂O: ~29 mg/mL
Aggregatzustand	solid
pka	7.48±0.10(Predicted)
Farbe	white
CAS Datenbank	51322-75-9(CAS DataBase Reference)
NIST chemische Informationen	Tizanidine(51322-75-9)

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	22-36/37/38
S-Sätze:	26-36
WGK Germany	3
RTECS-Nr.	DK9910000
Toxizität	LD50 orally in mice: 235 mg/kg (Sayers)

Gefahreninformationscode (GHS)

Tizanidine Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
Tizanidine is a centrally-acting muscle relaxant useful in the treatment of muscle spasms and a variety of spastic conditions.
Originator
Sandoz (Switzerland)
Verwenden
Tizanidine could have therapeutic use as a SARS-CoV-2 main protease inhibitor.
Verwenden
Labeled Tizanidine, intended for use as an internal standard for the quantification of Tizanidine by GC- or LC-mass spectrometry.
Definition
ChEBI: 2,1,3-Benzothiadiazole substituted at C-4 by a Delta1-imidazolin-2-ylamino group and at C-4 by a chloro group. It is an agonist at alpha2-adrenergic receptor sites.
Manufacturing Process
14 ml of benzoyl chloride are added to a solution of 11.5 g of ammonium thiocyanate in 150 ml of acetone in an ice bath and the mixture is then stirred for 10 min. This solution is heated to the boil at reflux together with 19 g of 4-amino-5-chloro-2,1,3-benzothiadiazole. The solution is cooled to room temperature and diluted with a 4-fold quantity of water. The precipitate is filtered off and rapidly brought to a boil together with 150 ml of a 2 N aqueous sodium hydroxide solution and kept at the boil for 5 min. The solution is cooled to room temperature, is acidified weakly with glacial acetic acid, the precipitate is filtered off, washed with ether and recrystallized from methanol. The N-(5-chloro-2,1,3-benzothiadiazol-4-yl)thiourea, obtained and this is boiled for 1 h together with 9 g of methyl iodide in 150 ml of methanol. After concentrating by evaporation, crude S-methyl-N-(5-chloro-2,1,3- benzothiadiazol-4-yl)isothiuronium iodide is obtained. 9.8 g of S-methyl-N-(5- chloro-2,1,3-benzothiadiazol-4-yl)isothiuronium iodide are heated to the boil at reflux for 1 h together with 50 ml of methanol and 1.8 ml of ethylene diamine. The solvent is then removed by evaporation and the moist residue is boiled at reflux for 1 h together with 20 ml of n-amyl alcohol. The mixture is subsequently shaken with 50 ml of chloroform and 150 ml of water until all the material is dissolved. 40 ml of a 2 N aqueous sodium hydroxide solution are added to the aqueous phase and extraction is effected with 200 ml of chloroform. The organic phase is dried and concentrated by evaporation. After recrystallizing the residue from methanol with the addition of some active charcoal, 4-(2-imidazolin-2-yl-amino)-5-chloro-2,1,3-benzothiadiazole, having a melting point of 221-223°C, is obtained. The 4-(2-imidazolin-2-yl-amino)-5-chloro-2,1,3-benzothiadiazole hydrochloride may be obtained by the teaction of 4-(2-imidazolin-2-yl-amino)-5-chloro- 2,1,3-benzothiadiazole with hydrochloric acid.
Trademarks
SIRDALUD
Therapeutic Function
Muscle relaxant, Spasmolytic
Mechanism of action
Tizanidine is a centrally active muscle relaxant analogue of clonidine that is approved for use in reducing spasticity associated with cerebral or spinal cord injury. Its mechanism of action for reducing spasticity suggests presynaptic inhibition of motor neurons at the α2-adrenergic receptor sites, reducing the release of excitatory amino acids and inhibiting facilitatory ceruleospinal pathways, thus resulting in a reduction in spasticity. Tizanidine only has a small fraction of the antihypertensive action of clonidine, presumably because of action at a selective subgroup of α2C-adrenoceptors, which appear to be responsible for the analgesic and antispasmodic activity of imidazoline α2-agonists(20).
Clinical Use
Tizanidine is a centrally acting adrenergic α2 receptor agonist used to treat chronic muscle spasticity conditions, such as multiple sclerosis.
Nebenwirkungen
Postulated mechanisms include α2 receptor-mediated decreased release of norepinephrine and serotonin from spinal interneurons. Tizanidine is structurally related to the α2 agonist clonidine that is used to treat hypertension; however, the blood pressure–lowering potency of tizanidine is approximately 10 to 20% that of clonidine. Nevertheless, patients may experience hypotension with tizanidine, together with muscle weakness, that may result in dizziness and falls in mobile patients. Tizanidine is rapidly and almost completely absorbed from the gastrointestinal tract; however, the estimated bioavailability is only 10 to 15% because of extensive first-pass metabolism, mainly by CYP1A2, which results in oxidative degradation of the imidazoline ring and hydroxylation of the aromatic system. Elevated liver enzyme values are not frequent with tizanidine use. Hepatic injury and death because of liver failure have been reported, however, and this complication should be considered in view of its marginal antispasmodic efficacy. Other frequently reported side effects of tizanidine are drowsiness and dry mouth. Clonidine also has been used to treat spasticity; however, even less high-quality clinical study data are available for this agent.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Anti-arrhythmics: enhanced muscle relaxant effect with procainamide.
Antibacterials: concentration increased by ciprofloxacin - avoid; concentration possibly increased by norfloxacin; concentration possibly reduced by rifampicin.
Antidepressants: concentration increased by fluvoxamine - avoid.
Antihypertensives: enhanced hypotensive effect.
Oral contraceptives: clearance of tizanidine reduced by 50
%.
Stoffwechsel
Tizanidine undergoes rapid and extensive first pass metabolism in the liver mainly via the cytochrome P450 isoenzyme CYP1A2. The metabolites (mainly inactive) constitute 70
% of the administered dose and are excreted via the renal route.

Tizanidine Upstream-Materialien And Downstream Produkte

Tizanidine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

51322-75-9, Tizanidine Verwandte Suche:

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