General
Preferred name
TIZANIDINE
Synonyms
TIZANIDINE HYDROCHLORIDE ()
Tizanidine HCl ()
DS 103-282 ()
Tizanidine (hydrochloride) ()
Tizanidine hydrochloride64461-82-1 ()
Sirdalud ()
Sirdalud MR ()
AN-021 ()
DS-103-282 ()
Tizanidine (as hydrochloride) ()
Zanaflex ()
AN021 ()
Tizanidine-d4 (hydrochloride) ()
P&D ID
PD009840
CAS
64461-82-1
51322-75-9
1188263-51-5
Tags
available
natural product
drug
Approved by
FDA
First approval
1996
Drug Status
investigational
approved
Drug indication
Spasm
Antispasmodic
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA
Tizanidine reduces spasticity by causing presynaptic inhibition of motor neurons via agonist actions at Alpha-2 adrenergic receptor sites.; This drug is centrally acting and leads to a reduction in the release of excitatory amino acids like glutamate and aspartate, which cause neuronal firing that leads to muscle spasm. The above reduction and excitatory neurotransmitter release results in presynaptic inhibition of motor neurons. The strongest effect of tizanidine has been shown to occur on spinal polysynaptic pathways. The anti-nociceptive and anticonvulsant activities of tizanidine may also be attributed to agonist action on Alpha-2 receptors. Tizanidine also binds with weaker affinity to the Alpha-1 receptors, explaining its slight and temporary effect on the cardiovascular system [T574].
INDICATION
Tizanidine is indicated for the relief of muscle spasticity, which can interfere with daily activities. The general recommendation is to reserve tizanidine use for periods of time when there is a particular need for relief, as it has a short duration of action [FDA label, F4471].
ROE
This drug is mainly eliminated by the kidney [FDA label].
HALF-LIFE
Approximately 2.5 hours [FDA label].
METABOLISM
About 95% of the ingested dose of tizanidine is metabolized. The main enzyme involved in the hepatic metabolism of tizanidine is CYP1A2 [FDA label].
DESCRIPTION
Tizanidine is a centrally acting α2-adrenoceptor agonist.
Marketed formulations may contain tizanidine hydrochloride (PubChem CID 114869). (GtoPdb)
Marketed formulations may contain tizanidine hydrochloride (PubChem CID 114869). (GtoPdb)
PHARMACODYNAMICS
**A note on spasticity**; ; Spasticity is an increase in muscle accompanied by uncontrolled, repetitive contractions of skeletal muscles which are involuntary.; The patient suffering from muscle spasticity may have reduced mobility and high levels of pain, contributing to poor quality of life and problems performing activities of personal hygiene and care [A177640]. ; ; **General effects**; ; Tizanidine is a rapidly acting drug used for the relief of muscle spasticity when it is required for performing specific activities. It acts as an agonist at Alpha-2 adrenergic receptor sites and relieves symptoms of muscle spasticity, allowing the continuation of normal daily activities. In animal models, tizanidine has not been shown to exert direct effects on skeletal muscle fibers or the neuromuscular junction, and has shown no significant effect on monosynaptic spinal reflexes (consisting of the communication between only 1 sensory neuron and 1 motor neuron) [L6064]. The frequency of muscle spasm and clonus are shown to be decreased by tizanidine [T574]. Tizanidine shows a stronger action on polysynaptic reflexes, which involve several interneurons (relay neurons) communicating with motor neurons stimulating muscle movement [L6064].; ; **Effects on blood pressure and heart rate**; ; This drug decreases heart rate and blood pressure in humans [A177559, A177589]. Despite this, rebound hypertension and tachycardia along with increased spasticity can occur when tizanidine is abruptly discontinued [A177643].
TOXICITY
**LD50 information** ; ; Oral LD50 (rat): 414 mg/kg; Subcutaneous LD50 (rat): 282 mg/kg; Oral LD50 (mouse): 235 mg/kg [MSDS]; ; **Use in pregnancy**; ; Animal studies have determined that this drug causes fetal harm [FDA label]. Studies have not been performed in humans, and it is advisable to ensure that tizanidine use in pregnant women should be reserved for cases in which possible benefit clearly outweighs the possible risk to mother and unborn child [F4471]. ; ; **Use in breastfeeding**; ; In studies of rat models, this tizanidine was found excreted in the breastmilk with a milk-to-blood ratio of 1.8:1 [FDA label]. In young nursing rats, abnormal results were obtained in tests indicative of central nervous system function. Various developmental changes that may have been attributable to the drug were observed. It is unknown whether tizanidine is excreted in human milk. It is a lipid-soluble drug, however, and likely to be excreted into breast milk [F4471]. ; ; **Carcinogenesis and mutagenesis**; ; No signs of carcinogenicity were observed in two dietary studies performed in rodent models. Tizanidine was given to mice for 78 weeks at doses reaching a maximum 16 mg/kg (equivalent to twice the maximum recommended human dose). In addition, the drug was given to rats for 104 weeks at doses reaching 9 mg/kg (equivalent to 2.5 times the maximum recommended human dose). There was a lack of a statistically significant increase in the occurrence of tumors in either study group [F4471].; ; Tizanidine was not found to be mutagenic or clastogenic in several laboratory essays, including the bacterial Ames test, the mammalian gene mutation test, in addition to the chromosomal aberration test in Chinese hamster cells and several other assays [F4471].; ;
ABSORPTION
This drug undergoes significant first-pass metabolism. After the administration of an oral dose, tizanidine is mostly absorbed. The absolute oral bioavailability of tizanidine is measured to be about 40% [FDA label]. ; ; **Effect of food on absorption**; ; Food has been shown to increase absorption for both the tablets and capsules. The increase in absorption with the tablet (about 30%) was noticeably higher than the capsule (~10%). When the capsule and tablet were administered with food, the amount absorbed from the capsule was about 80% of the amount absorbed from the tablet [FDA label]. It is therefore advisable to take this drug with food for increased absorption, especially in tablet form.
DESCRIPTION
Endogenous adenosine receptor agonist
(Tocris Bioactive Compound Library)
DESCRIPTION
alpha2 agonist
(Tocriscreen Plus)
DESCRIPTION
α2 agonist
(Tocriscreen Total)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
29
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Plus
Tocriscreen Total
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
65
Molecular Weight
253.02
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
1
Ring Count
3
Aromatic Ring Count
2
cLogP
1.72
TPSA
62.2
Fraction CSP3
0.22
Chiral centers
0.0
Largest ring
6.0
QED
0.81
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Pathway
GPCR/G protein
Neuronal Signaling
Target
??2 adrenergic receptor
ADRA2A, ADRA2B, ADRA2C, NISCH
Adrenergic Receptor
Primary Target
Adrenergic ?2 Receptors
MOA
Agonist
Adrenergic Receptor agonist
Indication
spasms
Therapeutic Class
Analgesics
Source data
