Tizanidine
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Also known as TizanidinaSID29216212SID29216213SID90340638SID26754628SID170465419SID144205429
Summary
Tizanidine (CHEMBL1079) is an approved small-molecule α-adrenergic agonist (ATC M03BX02) targeting ADRA2A and ADRA2B; indicated across 3 conditions including melanoma.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: M03BX02
- Targets: 2 (ADRA2A, ADRA2B)
- Indications: 3 conditions
- Clinical trials: 21
- Chemistry: 253.71 Da · C9H8ClN5S
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1079 |
| Name | Tizanidine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 5487 |
| ChEBI | CHEBI:63629 |
| ATC | M03BX02 |
| Molecular formula | C9H8ClN5S |
| Molecular weight | 253.71 |
| InChIKey | XFYDIVBRZNQMJC-UHFFFAOYSA-N |
SMILES: C1CN=C(N1)NC2=C(C=CC3=NSN=C32)Cl
IUPAC name: 5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine
ChEBI definition: 2,1,3-Benzothiadiazole substituted at C-4 by a Δ1-imidazolin-2-ylamino group and at C-4 by a chloro group. It is an agonist at α2-adrenergic receptor sites.
Pharmacological roles (ChEBI): α-adrenergic agonist, muscle relaxant.
Also known as: Tizanidina, Tizanidine, tizanidine, SID29216212, SID29216213, SID90340638, SID26754628, TIZANIDINE, SID170465419, SID144205429
Parent form; salt/anhydrous children: CHEMBL1200329
Patent coverage: 3,045 distinct patent families (12,099 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| ADRA2A | α2A-adrenoceptor | Agonist | 5.8 | 0.1% | P08913 |
| ADRA2B | α2B-adrenoceptor | Agonist | 5.8 | 0.2% | P18089 |
Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Nuclear receptor ROR-gamma, Prelamin-A/C, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, Alpha-1A adrenergic receptor, Nischarin, Alpha-1A adrenergic receptor.
Bioactivity
ChEMBL activities: 14 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| ADRA1A | 8.01 | AC50 | 9.8 | nM | CHEMBL_ACT_25229714 |
| NISCH | 7.55 | Ki | 28.31 | nM | CHEMBL_ACT_2564076 |
| NISCH | 7.55 | Ki | 28.3 | nM | CHEMBL_ACT_2564077 |
| ADRA2A | 7.07 | EC50 | 86 | nM | CHEMBL_ACT_16896928 |
| ADRA2A | 6.94 | AC50 | 114.7 | nM | CHEMBL_ACT_25220972 |
| ADRA2A | 6.87 | AC50 | 136.3 | nM | CHEMBL_ACT_25155905 |
| P18130 | 6.58 | EC50 | 264 | nM | CHEMBL_ACT_16896948 |
| ADRA2B | 6.53 | AC50 | 292.2 | nM | CHEMBL_ACT_25143585 |
| HRH2 | 6.03 | AC50 | 930 | nM | CHEMBL_ACT_25169235 |
| ADRA2C | 5.91 | EC50 | 1231 | nM | CHEMBL_ACT_16896938 |
| ADRA2A | 5.89 | AC50 | 1300 | nM | CHEMBL_ACT_25157074 |
| ADRA2C | 5.88 | AC50 | 1314 | nM | CHEMBL_ACT_25147756 |
| ADRA1A | 5.72 | AC50 | 1918 | nM | CHEMBL_ACT_25138397 |
| ADRA1A | 5.41 | AC50 | 3898 | nM | CHEMBL_ACT_25137863 |
Target pathways
Aggregated over 2 target gene(s): ADRA2A, ADRA2B.
Top Reactome pathways
19 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Hemostasis | 2 | ADRA2A, ADRA2B |
| Signal Transduction | 2 | ADRA2A, ADRA2B |
| Signaling by GPCR | 2 | ADRA2A, ADRA2B |
| Class A/1 (Rhodopsin-like receptors) | 2 | ADRA2A, ADRA2B |
| Amine ligand-binding receptors | 2 | ADRA2A, ADRA2B |
| GPCR downstream signalling | 2 | ADRA2A, ADRA2B |
| Adrenoceptors | 2 | ADRA2A, ADRA2B |
| Adrenaline signalling through Alpha-2 adrenergic receptor | 2 | ADRA2A, ADRA2B |
| G alpha (i) signalling events | 2 | ADRA2A, ADRA2B |
| G alpha (z) signalling events | 2 | ADRA2A, ADRA2B |
| GPCR ligand binding | 2 | ADRA2A, ADRA2B |
| Platelet activation, signaling and aggregation | 2 | ADRA2A, ADRA2B |
| Platelet Aggregation (Plug Formation) | 2 | ADRA2A, ADRA2B |
| Metabolism | 1 | ADRA2A |
| Integration of energy metabolism | 1 | ADRA2A |
| Metabolism of proteins | 1 | ADRA2A |
| Adrenaline,noradrenaline inhibits insulin secretion | 1 | ADRA2A |
| Regulation of insulin secretion | 1 | ADRA2A |
| Surfactant metabolism | 1 | ADRA2A |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| epidermal growth factor receptor signaling pathway | 2 |
| G protein-coupled receptor signaling pathway | 2 |
| adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | 2 |
| female pregnancy | 2 |
| negative regulation of norepinephrine secretion | 2 |
| regulation of vasoconstriction | 2 |
| platelet activation | 2 |
| negative regulation of epinephrine secretion | 2 |
| positive regulation of MAPK cascade | 2 |
| positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 2 |
| adrenergic receptor signaling pathway | 2 |
| adenylate cyclase-inhibiting adrenergic receptor signaling pathway | 2 |
| regulation of smooth muscle contraction | 2 |
| signal transduction | 2 |
| positive regulation of cytokine production | 1 |
Indications & clinical
Indications
3 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| melanoma | 1 | MONDO:0005105 | EFO:0000756 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 21.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 6 |
| PHASE3 | 4 |
| PHASE1 | 3 |
| EARLY_PHASE1 | 3 |
| Not specified | 3 |
| PHASE2 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05488847 | PHASE4 | ACTIVE_NOT_RECRUITING | Opioid-Free Pain Protocol After Shoulder Arthroplasty |
| NCT02016443 | PHASE4 | COMPLETED | Tizanidine and Pain After Herniorrhaphy |
| NCT02725359 | PHASE4 | COMPLETED | Tizanidine and Superficial Cervical Block on Pain After Thyroidectomy |
| NCT03068897 | PHASE4 | COMPLETED | Ibuprofen Plus Metaxolone, Tizanidine, or Baclofen for Low Back Pain |
| NCT06382662 | PHASE4 | COMPLETED | Assess the Effect of Metaxalone 640 mg (M640) Compared to Tizanidine 8 mg on Truck Driving Ability and Cognition |
| NCT07310628 | PHASE4 | COMPLETED | Comparison of Analgesic Efficacy of Intrathecal Levobupivacaine With and Without Oral Tizanidine in Lower Limb Surgeries: A Prospective Randomized Study |
| NCT05484349 | PHASE3 | RECRUITING | TIzanidine for the Preventive Treatment of Episodic MigrainE （TIME） |
| NCT06027099 | PHASE3 | RECRUITING | CARES (Comprehensive Analgesic, Recovery, and Education Support) for Surgery Trial |
| NCT00047580 | PHASE3 | COMPLETED | Comparison of Safety and Efficacy of Tizanidine Hydrochloride Capsules Versus Zanaflex® (Tizanidine Hydrochloride Tablets) Taken While in the Fed State (Just After a Meal) and in the Fasted State (Before a Meal) in Patients With Moderate to Severe Spasticity. |
| NCT06258785 | PHASE3 | COMPLETED | Effect of Tizanidine on Postoperative Urinary Retention After Sacrospinous Suspension |
| NCT01839279 | PHASE2 | COMPLETED | A Study to Define the ECG Effects of Tizanidine Compared to Placebo and the Positive Control, Moxifloxacin, in Healthy Men and Women Using a Blinded ECG Evaluator: A Thorough ECG Trial |
| NCT04429347 | PHASE2 | COMPLETED | Gabapentin and Tizanidine for Insomnia in Chronic Pain |
| NCT01065987 | PHASE1 | COMPLETED | Bioequivalence Study of Tizanidine HCl 4mg Tablets of Dr.Reddy’s Under Fed Conditions |
| NCT01146028 | PHASE1 | COMPLETED | Bioequivalence Study of Tizanidine HCl Tablets 4 mg of Dr.Reddys Under Fasting Conditions |
| NCT01844674 | PHASE1 | COMPLETED | A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies |
| NCT05789173 | EARLY_PHASE1 | RECRUITING | Interaction of CYP2B6 Genotype and Efavirenz With Methadone and Tizanidine PK |
| NCT05852093 | EARLY_PHASE1 | NOT_YET_RECRUITING | Clinical Study on the Effect of Tizanidine on the Function and Pain of Patients After Shoulder Arthroscopy |
| NCT06666673 | EARLY_PHASE1 | RECRUITING | Effect of Neural Constraints on Movement in Stroke |
| NCT02403687 | Not specified | COMPLETED | Prospective Analgesic Compound Efficacy (PACE) Study |
| NCT07022353 | Not specified | COMPLETED | Bi-level Erector Spinae Plane Block and Pre-emptive Oral Tizanidine for Analgesia After Mastectomy Surgery |
| NCT07309354 | Not specified | COMPLETED | Tizanidine and Acoustic Reflex |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
563 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ACLIDINIUM BROMIDE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| Afatinib | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| Almotriptan | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| CHENODIOL | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| CLOZAPINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| DESLORATADINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| NAPHAZOLINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| OLANZAPINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| OLODATEROL | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| PALIPERIDONE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| PRAMIPEXOLE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| TAMSULOSIN | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| TEGASEROD | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| VANCOMYCIN | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2B |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| ALFUZOSIN | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| AMIODARONE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| AMISULPRIDE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| APRACLONIDINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| ASENAPINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| AURANOFIN | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| AZELASTINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BENZQUINAMIDE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BENZTHIAZIDE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BITHIONOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BRIMONIDINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CHLOROQUINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CISAPRIDE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CLONIDINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| DANAZOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| DAPIPRAZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| DARIFENACIN | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
| DEXCHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2B |
Related Atlas pages
- Genes: ADRA2A, ADRA2B
- Drugs: Aclidinium Bromide, Afatinib, Almotriptan, Chenodiol, Clozapine, Crizotinib, Desloratadine, Dihydroergotamine, Naphazoline, Olanzapine, Olodaterol, Paliperidone, Pramipexole, Tamsulosin, Tegaserod, Vancomycin, Acetophenazine, Alfuzosin, Amiodarone, Amisulpride, Amitriptyline, Amoxapine, Apomorphine, Apraclonidine, Aripiprazole, Asenapine, Astemizole, Auranofin, Azelastine, Bazedoxifene, Benfluorex, Benperidol, Benzbromarone, Benzquinamide, Benzthiazide, Benztropine, Bithionol, Brexpiprazole, Brimonidine, Bromocriptine, Bromperidol, Cabergoline, Candesartan Cilexetil, Cariprazine, Carvedilol, Chlorhexidine, Chloroquine, Chlorpromazine, Cinnarizine, Cisapride, Clemastine, Clomipramine, Clonidine, Clotrimazole, Cyproheptadine, Danazol, Dapiprazole, Darifenacin, Dexchlorpheniramine