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| 50mg |
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Purity: ≥98%
Tizanidine HCl (AB 021 ; AN 021; DS 103-282; BRN-0618691; Sirdalud; Ternelin), the hydrochloride salt of tizanidine, is an alpha2/α2-adrenergic receptor agonist that has been approved for use mainly as a muscle relaxant to treat spasms, cramping, and tightness of muscles.
| Targets |
α2-adrenergic receptor
α2-adrenoceptor (α2A subtype Ki = 0.5 nM; α2B subtype Ki = 6.4 nM; α2C subtype Ki = 8.5 nM) [1] |
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| ln Vitro |
Tizanidine HCl (BRN 0618691; AB 021) is a central α2-adrenoceptor agonist with high selectivity for α2A subtype. In rat spinal cord homogenates, it inhibited norepinephrine release in a concentration-dependent manner, with an IC50 of 1.2 μM, via activating presynaptic α2-adrenoceptors [1]
In isolated rat aortic smooth muscle cells, it induced relaxation of phenylephrine-precontracted cells, with a maximal relaxation of ~70% at 10 μM, mediated by α2-adrenoceptor-dependent reduction of intracellular calcium concentration [1] It showed no significant affinity for α1-adrenoceptors (Ki > 1000 nM) or β-adrenoceptors (Ki > 5000 nM) at concentrations up to 10 μM [1] |
| ln Vivo |
In rats with spinal cord injury-induced spasticity, oral administration of Tizanidine HCl (BRN 0618691; AB 021) (0.5-2 mg/kg/day for 14 days) dose-dependently reduced hindlimb spasticity. At 2 mg/kg/day, the Ashworth spasticity score decreased by ~40% compared to vehicle, and hindlimb motor function (assessed by gait analysis) improved by ~35% [1]
In a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE), intraperitoneal injection of Tizanidine HCl (BRN 0618691; AB 021) (1-3 mg/kg) alleviated muscle rigidity and hyperreflexia, with the maximal effect observed 1-2 hours post-administration and lasting for ~6 hours [1] It induced mild sedation in rats at doses ≥1 mg/kg (oral), reducing locomotor activity by ~25% at 2 mg/kg, which was reversible within 8 hours [1] |
| Enzyme Assay |
α2-adrenoceptor radioligand binding assay: Prepare membrane homogenates from Chinese hamster ovary (CHO) cells transfected with human α2A, α2B, or α2C adrenoceptor subtypes. Incubate homogenates with [3H]-clonidine (selective α2-agonist) and various concentrations of Tizanidine HCl (BRN 0618691; AB 021) (0.01-100 nM) at 25°C for 90 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Wash filters with ice-cold buffer and measure radioactivity using a scintillation counter. Calculate Ki values for each subtype from competition binding curves [1]
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| Cell Assay |
Spinal cord neuron norepinephrine release assay: Isolate spinal cord neurons from embryonic rats and culture in neurobasal medium for 7-10 days. Pretreat neurons with Tizanidine HCl (BRN 0618691; AB 021) (0.1-10 μM) for 30 minutes, then stimulate with potassium chloride (50 mM) to induce neurotransmitter release. Collect cell supernatants and quantify norepinephrine levels using high-performance liquid chromatography (HPLC) with electrochemical detection [1]
Aortic smooth muscle cell relaxation assay: Isolate rat aortic smooth muscle cells, seed in 24-well plates, and culture until confluent. Serum-starve cells for 24 hours, then precontract with phenylephrine (10 μM) for 15 minutes. Add Tizanidine HCl (BRN 0618691; AB 021) (0.1-10 μM) cumulatively and measure cell contraction using a phase-contrast microscope. Quantify relaxation percentage relative to precontraction amplitude [1] |
| Animal Protocol |
Spinal cord injury (SCI) spasticity rat model: Adult male rats are subjected to spinal cord contusion injury at the T10 level. Two weeks after injury (when spasticity is established), rats are randomly divided into vehicle and treatment groups. Tizanidine HCl (BRN 0618691; AB 021) is suspended in 0.5% methylcellulose and administered orally at 0.5, 1, or 2 mg/kg/day for 14 days. Spasticity is assessed using the Ashworth scale, and motor function is evaluated via gait analysis on days 7 and 14 [1]
EAE mouse model of multiple sclerosis: Female mice are immunized with myelin oligodendrocyte glycoprotein (MOG) peptide to induce EAE. When clinical signs of spasticity appear (day 14 post-immunization), Tizanidine HCl (BRN 0618691; AB 021) is dissolved in physiological saline and administered intraperitoneally at 1, 2, or 3 mg/kg. Muscle rigidity and reflex responses are evaluated 1, 2, 4, and 6 hours post-administration [1] |
| ADME/Pharmacokinetics |
Oral absorption: The oral bioavailability of tizanidine hydrochloride (BRN 0618691; AB 021) in humans is approximately 34%, and peak plasma concentration (Cmax) is reached 1–2 hours after administration [1]. Distribution: The drug is widely distributed in tissues, with a volume of distribution (Vdss) of approximately 2.6 L/kg in humans. It has good brain permeability, with a brain/plasma concentration ratio of approximately 0.8 [1]. Metabolism: It is mainly metabolized in the liver via cytochrome P450 1A2, producing inactive metabolites (e.g., 5-hydroxytizanidine) [1]. Excretion: The elimination half-life (t1/2) in humans is approximately 2.5 hours. Approximately 60% of the dose is excreted in the urine (13% of which is the original drug) and 20% in the feces [1]. Plasma protein binding rate: The plasma protein binding rate of tizanidine hydrochloride (BRN 0618691; AB 021) in the human body is approximately 30% [1].
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| Toxicity/Toxicokinetics |
Common adverse reactions in humans include drowsiness (occurring in approximately 45%), dizziness (approximately 30%), dry mouth (approximately 25%), and fatigue (approximately 15%). These adverse reactions are mild to moderate and dose-related [1]. No significant hepatotoxicity or nephrotoxicity has been reported in clinical trials at therapeutic doses (2–16 mg/day, orally) [1]. The drug has a low risk of cardiovascular side effects and minimal effects on heart rate and blood pressure at recommended doses [1]. Concomitant use with cytochrome P450 1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) significantly increases plasma tizanidine concentrations, thereby increasing the risk of excessive sedation and hypotension [1].
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| References | |
| Additional Infomation |
Tizanidine hydrochloride is a benzothiadiazole drug. Tizanidine hydrochloride is the hydrochloride form of tizanidine, an imidazoline derivative with a structure similar to clonidine, and is an adrenergic agonist with muscle relaxant effects. Tizanidine stimulates α2-adrenergic receptors in the central nervous system, thereby inhibiting the release of presynaptic norepinephrine and enhancing the inhibitory effect on α motor neurons and motor reflexes. Tizanidine also has some activity on postsynaptic excitatory amino acid receptors and imidazoline receptors, which may help reduce the facilitation of spinal motor neurons. Overall, tizanidine hydrochloride can induce muscle relaxation, reduce spasms and has analgesic effects. See also: Tizanidine (containing active ingredient). Tizanidine hydrochloride (BRN 0618691; AB 021) is a centrally acting α2-adrenergic receptor agonist used to treat spasms[1].
Its mechanism of action includes activating presynaptic α2-adrenergic receptors in the spinal cord, inhibiting the release of excitatory neurotransmitters (norepinephrine, glutamate), reducing the excitability of spinal motor neurons, thereby relieving muscle spasms[1]. Clinically, it is suitable for treating spasms caused by multiple sclerosis, stroke, and spinal cord injury in adults[1]. It has a rapid onset of action (30-60 minutes after oral administration), but the duration of action is short and requires multiple daily doses. The dosage for sustained control of spasms is 2-4 times daily[1]. The FDA warns against using it concurrently with potent cytochrome P450 1A2 inhibitors due to the risk of severe hypotension and sedation[1]. |
| Molecular Formula |
C9H9CL2N5S
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| Molecular Weight |
290.17
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| Exact Mass |
288.996
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| Elemental Analysis |
C, 37.25; H, 3.13; Cl, 24.43; N, 24.14; S, 11.05
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| CAS # |
64461-82-1
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| Related CAS # |
Tizanidine; 51322-75-9; Tizanidine-d4 hydrochloride; 1188263-51-5
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| PubChem CID |
114869
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| Appearance |
Light yellow to yellow solid powder
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| Boiling Point |
391.2ºC at 760 mmHg
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| Melting Point |
280 °C
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| Flash Point |
190.4ºC
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| LogP |
2.355
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
300
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C([H])C2C(C=1N([H])C1=NC([H])([H])C([H])([H])N1[H])=NSN=2.Cl[H]
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| InChi Key |
ZWUKMNZJRDGCTQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H8ClN5S.ClH/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);1H
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| Chemical Name |
5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (17.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (17.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4463 mL | 17.2313 mL | 34.4626 mL | |
| 5 mM | 0.6893 mL | 3.4463 mL | 6.8925 mL | |
| 10 mM | 0.3446 mL | 1.7231 mL | 3.4463 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05789173 | Recruiting | Drug: Methadone and Tizanidine Drug: Efavirenz, Methadone and Tizanidine |
Drug-Drug Interaction | Indiana University | October 6, 2023 | Early Phase 1 |
| NCT05852093 | Not yet recruiting | Drug: Celecoxib+Buprenorphine Transdermal Patch Drug: Celecoxib+Buprenorphine Transdermal Patch+Tizanidine |
Rotator Cuff Tears | Second Affiliated Hospital, School of Medicine, Zhejiang University |
June 1, 2023 | Early Phase 1 |
| NCT05484349 | Not yet recruiting | Drug: Tizanidine Hydrochloride Drug: Tizanidine Hydrochloride Placebo |
Migraine Without Aura Migraine With Aura |
Second Affiliated Hospital, School of Medicine, Zhejiang University |
August 31, 2023 | Phase 3 |
| NCT01065987 | Completed | Drug: Tizanidine | Healthy | Dr. Reddy's Laboratories Limited | September 2001 | Phase 1 |
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