tizanidine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
2683 51322-75-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • DS 103-282
  • tizanidine
  • tizanidine hydrochloride
  • tizanidine HCl
  • AN021
  • DS103-282
Tizanidine is an agonist at alpha2-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.
  • Molecular weight: 253.71
  • Formula: C9H8ClN5S
  • CLOGP: 2.32
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 2
  • TPSA: 62.20
  • ALOGS: -3.28
  • ROTB: 1

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
12 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 2.36 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 21 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 2.40 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 11 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.70 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 2.40 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 27, 1996 FDA ACORDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Completed suicide 795.16 33.71 197 950 20837 2336101
Drug hypersensitivity 415.65 33.71 143 1004 46500 2310438
Somnolence 390.21 33.71 116 1031 23369 2333569
Coma 348.86 33.71 87 1060 8969 2347969
Pneumonia aspiration 338.00 33.71 72 1075 3670 2353268
Toxicity to various agents 331.94 33.71 111 1036 32643 2324295
Gastrooesophageal reflux disease 274.39 33.71 72 1075 9023 2347915
Hypotension 191.46 33.71 74 1073 32362 2324576
Cardio-respiratory arrest 158.49 33.71 47 1100 9099 2347839
Respiratory arrest 153.16 33.71 42 1105 6136 2350802
Drug withdrawal syndrome 117.79 33.71 35 1112 6786 2350152
Drug interaction 108.51 33.71 48 1099 29115 2327823
Cardiac arrest 105.47 33.71 39 1108 14891 2342047
Dizziness 103.29 33.71 58 1089 58607 2298331
Muscle spasms 91.55 33.71 39 1108 21527 2335411
Intentional overdose 81.43 33.71 30 1117 11291 2345647
Overdose 81.16 33.71 35 1112 19872 2337066
Bradycardia 73.80 33.71 27 1120 9954 2346984
Poisoning 68.93 33.71 19 1128 2801 2354137
Fall 65.31 33.71 40 1107 47059 2309879
Drug abuse 61.91 33.71 25 1122 12001 2344937
Muscular weakness 60.01 33.71 26 1121 14871 2342067
Suicide attempt 56.50 33.71 23 1124 11259 2345679
Nausea 54.96 33.71 51 1096 112138 2244800
Loss of consciousness 54.26 33.71 26 1121 18741 2338197
Syncope 53.76 33.71 25 1122 16850 2340088
Urinary tract infection 53.47 33.71 30 1117 29912 2327026
Confusional state 50.67 33.71 27 1120 24317 2332621
Orthostatic hypotension 50.58 33.71 15 1132 2864 2354074
Blood pressure decreased 50.28 33.71 20 1127 9216 2347722
Drug ineffective 47.40 33.71 45 1102 101579 2255359
Tremor 46.06 33.71 24 1123 20637 2336301
Sinus bradycardia 45.94 33.71 13 1134 2103 2354835
Death 43.61 33.71 39 1108 81429 2275509
Asthenia 43.40 33.71 31 1116 46895 2310043
Hypoaesthesia 40.85 33.71 22 1125 20193 2336745
Multiple sclerosis relapse 40.46 33.71 18 1129 10925 2346013
Hypertension 39.75 33.71 24 1123 27337 2329601
Muscle spasticity 39.73 33.71 11 1136 1642 2355296
Alanine aminotransferase increased 39.18 33.71 19 1128 14013 2342925
Depression 39.14 33.71 24 1123 28108 2328830
Insomnia 38.45 33.71 23 1124 25764 2331174
Product complaint 36.18 33.71 13 1134 4525 2352413
Vomiting 35.76 33.71 33 1114 71569 2285369
Anxiety 35.70 33.71 23 1124 29336 2327602
Headache 34.44 33.71 34 1113 80145 2276793

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Completed suicide 265.09 41.80 72 391 16240 1730078
Toxicity to various agents 140.05 41.80 51 412 29090 1717228
Hypotension 117.02 41.80 45 418 29609 1716709
Cardio-respiratory arrest 104.09 41.80 31 432 9262 1737056
Drug interaction 97.97 41.80 39 424 27919 1718399
Respiratory arrest 85.36 41.80 24 439 5815 1740503
Cardiac arrest 72.59 41.80 27 436 15903 1730415
Drug hypersensitivity 48.79 41.80 20 443 15115 1731203
Bradycardia 48.37 41.80 18 445 10516 1735802
Poisoning 44.21 41.80 12 451 2520 1743798

Pharmacologic Action:

SourceCodeDescription
ATC M03BX02 MUSCULO-SKELETAL SYSTEM
MUSCLE RELAXANTS
MUSCLE RELAXANTS, CENTRALLY ACTING AGENTS
Other centrally acting agents
MeSH PA D018663 Adrenergic Agents
MeSH PA D000322 Adrenergic Agonists
MeSH PA D058647 Adrenergic alpha-2 Receptor Agonists
FDA MoA N0000009918 Adrenergic alpha2-Agonists
FDA EPC N0000175554 Central alpha-2 Adrenergic Agonist
MeSH PA D000316 Adrenergic alpha-Agonists
MeSH PA D000700 Analgesics
CHEBI has role CHEBI:35569 alpha-adrenergic agonist
CHEBI has role CHEBI:51371 muscle relaxant
MeSH PA D000927 Anticonvulsants
MeSH PA D002491 Central Nervous System Agents
MeSH PA D009125 Muscle Relaxants, Central
MeSH PA D009465 Neuromuscular Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D010276 Parasympatholytics
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018689 Sensory System Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Spasticity indication 221360009
Muscle spasticity of spinal origin indication 416830008
Muscle Spasticity of Cerebral Origin indication
Low blood pressure contraindication 45007003
Bradycardia contraindication 48867003
Hepatic failure contraindication 59927004
Psychotic disorder contraindication 69322001
Kidney disease contraindication 90708001 DOID:557

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.01 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Alpha-2C adrenergic receptor GPCR AGONIST WOMBAT-PK CHEMBL
Alpha-2B adrenergic receptor GPCR AGONIST WOMBAT-PK CHEMBL
Alpha-2A adrenergic receptor GPCR AGONIST WOMBAT-PK CHEMBL
Nischarin Membrane receptor Ki 7.55 CHEMBL

External reference:

IDSource
4021025 VUID
N0000148492 NUI
C0146011 UMLSCUI
D00776 KEGG_DRUG
6AI06C00GW UNII
4697 INN_ID
108461005 SNOMEDCT_US
4021025 VANDF
57258 RXNORM
d04102 MMSL
5589 MMSL
373440006 SNOMEDCT_US
006021 NDDF
64461-82-1 SECONDARY_CAS_RN
CHEBI:63629 CHEBI
CHEMBL1079 ChEMBL_ID
DB00697 DRUGBANK_ID
CHEMBL1200329 ChEMBL_ID
5487 PUBCHEM_CID
7308 IUPHAR_LIGAND_ID
C023754 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
tizanidine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0185-0034 TABLET 2 mg ORAL ANDA 17 sections
tizanidine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0185-4400 TABLET 4 mg ORAL ANDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 0378-0722 TABLET 2 mg ORAL ANDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 0378-0724 TABLET 4 mg ORAL ANDA 17 sections
tizanidine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0591-2788 CAPSULE, GELATIN COATED 2 mg ORAL NDA 17 sections
tizanidine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0591-2789 CAPSULE, GELATIN COATED 4 mg ORAL NDA 17 sections
tizanidine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0591-2790 CAPSULE, GELATIN COATED 6 mg ORAL NDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 0615-5574 TABLET 4 mg ORAL ANDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 0615-6564 TABLET 2 mg ORAL ANDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 0615-7996 TABLET 4 mg ORAL ANDA 14 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 0615-8274 TABLET 4 mg ORAL ANDA 17 sections
tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 0904-6418 TABLET 4 mg ORAL ANDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 0904-6898 TABLET 4 mg ORAL ANDA 17 sections
Zanaflex HUMAN PRESCRIPTION DRUG LABEL 1 10144-594 TABLET 4 mg ORAL NDA 18 sections
Zanaflex HUMAN PRESCRIPTION DRUG LABEL 1 10144-602 CAPSULE 2 mg ORAL NDA 18 sections
Zanaflex HUMAN PRESCRIPTION DRUG LABEL 1 10144-604 CAPSULE 4 mg ORAL NDA 18 sections
Zanaflex HUMAN PRESCRIPTION DRUG LABEL 1 10144-606 CAPSULE 6 mg ORAL NDA 18 sections
tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 10544-576 TABLET 4 mg ORAL ANDA 17 sections
tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 10544-587 TABLET 2 mg ORAL ANDA 17 sections
tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 10544-863 TABLET 2 mg ORAL ANDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 10544-890 TABLET 4 mg ORAL ANDA 12 sections
TIZANIDINE HUMAN PRESCRIPTION DRUG LABEL 1 16590-220 TABLET 2 mg ORAL ANDA 15 sections
TIZANIDINE HUMAN PRESCRIPTION DRUG LABEL 1 16590-221 TABLET 4 mg ORAL ANDA 15 sections
ZANAFLEX HUMAN PRESCRIPTION DRUG LABEL 1 16590-756 CAPSULE 6 mg ORAL NDA 21 sections
ZANAFLEX HUMAN PRESCRIPTION DRUG LABEL 1 16590-871 CAPSULE 4 mg ORAL NDA 21 sections
Zanaflex HUMAN PRESCRIPTION DRUG LABEL 1 21695-373 CAPSULE, GELATIN COATED 4 mg ORAL NDA 14 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 29300-168 TABLET 2 mg ORAL ANDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 29300-169 TABLET 4 mg ORAL ANDA 17 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 33261-103 TABLET 2 mg ORAL ANDA 11 sections
Tizanidine HUMAN PRESCRIPTION DRUG LABEL 1 33261-104 TABLET 4 mg ORAL ANDA 11 sections