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Showing drug card for Tizanidine (DB00697)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:03
Primary Accession Number DB00697
Secondary Accession Number
  • APRD00128
Name Tizanidine
Drug Type
  • Approved
  • Small Molecule
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.
Synonyms
  1. Tizanidina [INN-Spanish]
  2. Tizanidine Hcl
  3. Tizanidinum [INN-Latin]
Brand Names
  1. Sirdalud
  2. Ternelin
  3. Zanaflex
Brand Mixtures Not Available
Chemical IUPAC Name 6-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-7-amine
Chemical Formula C9H8ClN5S
Chemical Structure Structure
CAS Registry Number 51322-75-9
InChI Identifier InChI=1/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)/f/h11,13H
InChI Key XFYDIVBRZNQMJC-KZZMUEETCJ
KEGG Drug Not Available
KEGG Compound C07452 Link Image
PubChem Compound 5487 Link Image
PubChem Substance 180932 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02259893 Link Image
RxList Link http://www.rxlist.com/cgi/generic/tizanidine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Tizanidine Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 253.7110
Monoisotopic Molecular Weight 253.0189
State Solid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 1.33e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1.4 Source: PhysProp
Predicted LogP 1.60 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.28 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES ClC1=C(NC2=NCCN2)C2=NSN=C2C=C1
Canonical SMILES ClC1=C(NC2=NCCN2)C2=NSN=C2C=C1
Drug Category
  • Adrenergic alpha-Agonists
  • Analgesics
  • Anticonvulsants
  • Muscle Relaxants
  • Muscle Relaxants, Central
  • Parasympatholytics
  • Skeletal Muscle Relaxants
ATC Codes
AHFS Codes
  • 12:20.00
Indication For the management of increased muscle tone associated with spasticity
Pharmacology 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.
Mechanism of Action Tizanidine reduces spasticity by increasing presynaptic inhibition of motor neurons through agonist action at a2-adrenergic receptor sites.
Absorption Not Available
Toxicity Not Available
Protein Binding 30%
Biotransformation Not Available
Half Life 2.5 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Amiodarone Amiodarone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Amlodipine Amlopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Benazepril Tizanidine increases the risk of hypotension with the ACE inhibitor
Captopril Tizanidine increases the risk of hypotension with the ACE inhibitor
Cilazapril Tizanidine increases the risk of hypotension with the ACE inhibitor
Cimetidine Cimetidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Ciprofloxacin Ciprofloxacin increases the effect/toxicity of tizanidine
Ciprofloxacin Ciprofloxacin inhibits the metabolism and clearance of Tizanidine. Concomitant therapy is contraindicated.
Diclofenac Diclofenac may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Donepezil Possible antagonism of action
Enalapril Tizanidine increases the risk of hypotension with the ACE inhibitor
Ethanol Ethanol increases the adverse effects of Tizanidine. The CNS depressant effects of these agents are additive.
Ethinyl Estradiol Oral contraceptives decrease the clearance of Tizanidine.
Ethinyl Estradiol The contraceptive increases the effect of tizanidine
Fluoxetine Fluoxetine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Fluvoxamine Fluvoxamine increases the effect/toxicity of tizanidine
Fluvoxamine Fluvoxamine inhibits the metabolism and clearance of Tizanidine. Concomitant therapy is contraindicated.
Fosinopril Tizanidine increases the risk of hypotension with the ACE inhibitor
Galantamine Possible antagonism of action
Gemfibrozil Gemfibrozil may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Ketoconazole Ketoconazole may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Lidocaine Lidocaine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Lisinopril Tizanidine increases the risk of hypotension with the ACE inhibitor
Mestranol Oral contraceptives decrease the clearance of Tizanidine.
Mestranol The contraceptive increases the effect of tizanidine
Methoxsalen Methoxsalen may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Mexiletine Mexilitene may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Miconazole Miconazole may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Moexipril Tizanidine increases the risk of hypotension with the ACE inhibitor
Moxifloxacin Moxifloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Nifedipine Nifedipine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Norethindrone The contraceptive increases the effect of tizanidine
Norfloxacin Norfloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Ofloxacin Ofloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Perindopril Tizanidine increases the risk of hypotension with the ACE inhibitor
Primaquine Primaquine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Propafenone Propafenone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Propofol Propofol may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Quinapril Tizanidine increases the risk of hypotension with the ACE inhibitor
Quinupristin This combination presents an increased risk of toxicity
Ramipril Tizanidine increases the risk of hypotension with the ACE inhibitor
Rivastigmine Possible antagonism of action
Spirapril Tizanidine increases the risk of hypotension with the ACE inhibitor
Thiabendazole Thiabendazole may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Ticlopidine Ticlopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Trandolapril Tizanidine increases the risk of hypotension with the ACE inhibitor
Tranylcypromine Tranylcypromine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 1A2 (CYP1A2)
Targets
  1. Alpha-2A adrenergic receptor
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 1A2 (CYP1A2)
Enzyme 1 Gene Name CYP1A2
Enzyme 1 SwissProt ID P05177 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >P05177|CP1A2_HUMAN Cytochrome P450 1A2 - Homo sapiens (Human). 
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Drug Target 1 [top]
Target 1 ID 318
Target 1 Name Alpha-2A adrenergic receptor
Target 1 Synonyms
  1. Alpha-2 adrenergic receptor subtype C10
  2. Alpha-2A adrenoceptor
  3. Alpha-2A adrenoreceptor
  4. Alpha-2AAR
Target 1 Gene Name ADRA2A
Target 1 Protein Sequence >Alpha-2A adrenergic receptor 
MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT
SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS
IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG
PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA
APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD
HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS
RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS
LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Target 1 Number of Residues 457
Target 1 Molecular Weight 48957
Target 1 Theoretical pI 10.20
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha2-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in alpha2-adrenergic receptor activity
Target 1 Specific Function Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 34-59
  • 71-96
  • 107-129
  • 150-173
  • 193-217
  • 375-399
  • 407-430
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 178196 Link Image
Target 1 UniProtKB/Swiss-Prot ID P08913 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ADA2A_HUMAN Link Image
Target 1 PDB ID 1HOF Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1353 bp 
ATGGGCTCCCTGCAGCCGGACGCGGGCAACGCGAGCTGGAACGGGACCGAGGCGCCGGGG
GGCGGCGCCCGGGCCACCCCTTACTCCCTGCAGGTGACGCTGACGCTGGTGTGCCTGGCC
GGCCTGCTCATGCTGCTCACCGTGTTCGGCAACGTGCTCGTCATCATCGCCGTGTTCACG
AGCCGCGCGCTCAAGGCGCCCCAAAACCTCTTCCTGGTGTCTCTGGCCTCGGCCGACATC
CTGGTGGCCACGCTCGTCATCCCTTTCTCGCTGGCCAACGAGGTCATGGGCTACTGGTAC
TTCGGCAAGGCTTGGTGCGAGATCTACCTGGCGCTCGACGTGCTCTTCTGCACGTCGTCC
ATCGTGCACCTGTGCGCCATCAGCCTGGACCGCTACTGGTCCATCACACAGGCCATCGAG
TACAACCTGAAGCGCACGCCGCGCCGCATCAAGGCCATCATCATCACCGTGTGGGTCATC
TCGGCCGTCATCTCCTTCCCGCCGCTCATCTCCATCGAGAAGAAGGGCGGCGGCGGCGGC
CCGCAGCCGGCCGAGCCGCGCTGCGAGATCAACGACCAGAAGTGGTACGTCATCTCGTCG
TGCATCGGCTCCTTCTTCGCTCCCTGCCTCATCATGATCCTGGTCTACGTGCGCATCTAC
CAGATCGCCAAGCGTCGCACCCGCGTGCCACCCAGCCGCCGGGGTCCGGACGCCGTCGCC
GCGCCGCCGGGGGGCACCGAGCGCAGGCCCAACGGTCTGGGCCCCGAGCGCAGCGCGGGC
CCGGGGGGCGCAGAGGCCGAACCGCTGCCCACCCAGCTCAACGGCGCCCCTGGCGAGCCC
GCGCCGGCCGGGCCGCGCGACACCGACGCGCTGGACCTGGAGGAGAGCTCGTCTTCCGAC
CACGCCGAGCGGCCTCCAGGGCCCCGCAGACCCGAGCGCGGTCCCCGGGGCAAAGGCAAG
GCCCGAGCGAGCCAGGTGAAGCCGGGCGACAGCCTGCGCGGCGCGGGCCGGGGGCGACGG
GGATCGGGACGCCGGCTGCAGGGCCGGGGGAGGAGCGCGTCGGGGCTGCCAAGGCGTCGC
GCTGGCGCGGGCGGGCAGAACCGCGAGAAGCGCTTCACGTTCGTGCTGGCCGTGGTCATC
GGAGTGTTCGTGGTGTGCTGGTTCCCCTTCTTCTTCACCTACACGCTCACGGCCGTCGGG
TGCTCCGTGCCACGCACGCTCTTCAAATTCTTCTTCTGGTTCGGCTACTGCAACAGCTCG
TTGAACCCGGTCATCTACACCATCTTCAACCACGATTTCCGCCGCGCCTTCAAGAAGATC
CTCTGTCGGGGGGACAGGAAGCGGATCGTGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ADRA2A Link Image
Target 1 GenAtlas ID ADRA2A Link Image
Target 1 HGNC ID HGNC:281 Link Image
Target 1 Chromosome Location 10
Target 1 Locus 10q24-q26
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Chung DA, Zuiderweg ER, Fowler CB, Soyer OS, Mosberg HI, Neubig RR: NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix. Biochemistry. 2002 Mar 19;41(11):3596-604. [PubMed Link Image]
  2. Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK: A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists. J Biol Chem. 1991 Aug 15;266(23):15488-92. [PubMed Link Image]
  3. Wang CD, Buck MA, Fraser CM: Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists. Mol Pharmacol. 1991 Aug;40(2):168-79. [PubMed Link Image]
  4. Chhajlani V, Rangel N, Uhlen S, Wikberg JE: Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR. FEBS Lett. 1991 Mar 25;280(2):241-4. [PubMed Link Image]
  5. Guyer CA, Horstman DA, Wilson AL, Clark JD, Cragoe EJ Jr, Limbird LE: Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs. J Biol Chem. 1990 Oct 5;265(28):17307-17. [PubMed Link Image]
  6. Fraser CM, Arakawa S, McCombie WR, Venter JC: Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation. J Biol Chem. 1989 Jul 15;264(20):11754-61. [PubMed Link Image]
  7. Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW: Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987 Oct 30;238(4827):650-6. [PubMed Link Image]
Target 1 Drug References
  1. Piletz JE, Zhu H, Chikkala DN: Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J Pharmacol Exp Ther. 1996 Nov;279(2):694-702. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.