Last updated

Clinical data
Pronunciation /tˈzænɪdn/ tye-ZAN-i-deen
Trade names Zanaflex, Sirdalud, and others
Other names4-Chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-8-thia-7,9-diazabicyclo[4.3.0]nona-2,4,6,9-tetraen-5-amine
AHFS/Drugs.com Monograph
MedlinePlus a601121
License data
Routes of
By mouth
Drug class α2-adrenergic receptor agonist
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~40% [1]
Protein binding ~30%
Metabolism Liver (CYP1A2, 95%)
Elimination half-life 2.54 hours (tizanidine), 20–40 hours (inactive metabolites) [1]
Excretion Urine (60%), feces (20%)
  • 5-Chloro-N-(4,5-dihydro-1H-imidazol-2-yl)benzo[c] [1,2,5]thiadiazol-4-amine
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard 100.125.400 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C9H8ClN5S
Molar mass 253.71 g·mol−1
3D model (JSmol)
  • Clc1ccc3nsnc3c1NC/2=N/CCN\2
  • InChI=1S/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) Yes check.svgY

Tizanidine, sold under the brand name Zanaflex among others, is an alpha-2 (α2) adrenergic receptor agonist, [2] similar to clonidine, that is used to treat muscle spasticity due to spinal cord injury, multiple sclerosis, and spastic cerebral palsy. [3] Effectiveness appears similar to baclofen or diazepam. [4] It is taken by mouth. [5]


Common side effects of tizanidine include dry mouth, sleepiness, weakness, and dizziness. [5] Serious side effects may include low blood pressure, liver problems, psychosis, and QT prolongation. [5] It is unclear if use in pregnancy and breastfeeding is safe. [6] It is an α2-adrenergic agonist, but how it works is not entirely clear. [5]

Tizanidine was approved for medical use in the United States in 1996. [5] It is available as a generic medication. [3] In 2020, it was the 84th most commonly prescribed medication in the United States, with more than 8 million prescriptions. [7] [8]

Medical uses

Tizanidine has been found to be as effective as other antispasmodic drugs and is more tolerable than baclofen and diazepam. [4]

Side effects

Side effects include dizziness, drowsiness, weakness, nervousness, confusion, hallucinations, strange dreams, depression, vomiting, dry mouth, constipation, diarrhea, stomach pain, heartburn, increased muscle spasms, back pain, rash, sweating, and a tingling sensation in the arms, legs, hands, and feet. [9]

Symptoms of overdose in 45 cases reported to a poison control center included: lethargy, bradycardia, hypotension, agitation, confusion, vomiting and coma. [10]


Concomitant use of tizanidine and moderate or potent CYP1A2 inhibitors (such as zileuton, certain antiarrhythmics (amiodarone, mexiletine, propafenone, verapamil), cimetidine, famotidine, aciclovir, ticlopidine and oral contraceptives) is contraindicated. Concomitant use of tizanidine with fluvoxamine, a potent CYP1A2 inhibitor in humans, resulted in a 33-fold increase in the tizanidine AUC (plasma drug concentration-time curve). [1] For this reason both fluvoxamine and tizanidine should not be taken at the same time. Fluoroquinolone antibiotics such as moxifloxacin, levofloxacin, and ciprofloxacin should also be avoided due to an increased serum concentration of tizanidine when administered concomitantly. [11] Tizanidine has the potential to interact with other central nervous system depressants. Alcohol should be avoided, particularly as it can upset the stomach. The CNS-depressant effects of tizanidine and alcohol are additive. [1] Caution with the following interactions: [12] [13] [14]


Tizanidine is an α2 receptor agonist closely related to clonidine. It has approximately one tenth to one fifteenth of the blood pressure lowering effect of clonidine. The relation between the α2 receptor agonism and the spasmolytic action is still not fully understood. [2]

SiteKi (nM)SpeciesRef
α2A 62Human [15]
α2B 75 OK [15]
α2C 76Rat [15]

Route of administration

Tizanidine is available as a tablet or capsule. Capsules may be opened and sprinkled on food. However, this may change the absorption of the medication compared to taking the capsule whole. [16] It has a volume of distribution of 2.4 L/kg following intravenous administration. [1]


Tizanidine is a derivative of 2,1,3-benzothiadiazole and its first published synthesis was reported in a patent. [17] The 5-chloro-2,1,3-benzothiadiazol-4-amine intermediate was a known compound, produced in three steps from 4-chlorophenylenediamine as shown. [18] Treatment with two equivalents of thionyl chloride in pyridine formed the heterocycle, which was nitrated with sodium nitrate in sulfuric acid and reduced using iron and acetic acid.

Tizanidine synthesis US3843668.svg

The amine intermediate was treated with benzoyl chloride and ammonium thiocyanate followed by alkaline hydrolysis to form a thiourea. This was activated as its isothiuronium salt before being treated with ethylene diamine to give tizanidine. [17] [19]

See also

Related Research Articles

An antipyretic is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which results in a reduction in fever.

A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics. Neuromuscular blockers act by interfering with transmission at the neuromuscular end plate and have no central nervous system (CNS) activity. They are often used during surgical procedures and in intensive care and emergency medicine to cause temporary paralysis. Spasmolytics, also known as "centrally acting" muscle relaxant, are used to alleviate musculoskeletal pain and spasms and to reduce spasticity in a variety of neurological conditions. While both neuromuscular blockers and spasmolytics are often grouped together as muscle relaxant, the term is commonly used to refer to spasmolytics only.

<span class="mw-page-title-main">Mirtazapine</span> Antidepressant medication

Mirtazapine, sold under the brand name Remeron amongst others, is an atypical tetracyclic antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is often used in cases of depression complicated by anxiety or insomnia. The effectiveness of mirtazapine is comparable to other commonly prescribed antidepressants. It is taken by mouth.

<span class="mw-page-title-main">Clonidine</span> Medication for high blood pressure

Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal, menopausal flushing, diarrhea, spasticity, and certain pain conditions. It is used orally, by injection, or as a transdermal skin patch. Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.

<span class="mw-page-title-main">Baclofen</span> Medication for muscle movement disorders

Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life, and off-label to treat alcohol use disorder or opioid withdrawal symptoms. It is taken orally or by intrathecal pump. It is also sometimes used transdermally in combination with gabapentin and clonidine prepared at a compounding pharmacy.

<span class="mw-page-title-main">Oxymetazoline</span> Topical decongestant

Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eyedrops to treat eye redness due to minor irritation, and as a prescription topical cream to treat persistent facial redness due to rosacea in adults. Its effects begin within minutes and last for up to six hours. Intranasal use for longer than three days may cause congestion to recur or worsen, resulting in physical dependence.

An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors. The five main categories of adrenergic receptors are: α1, α2, β1, β2, and β3, although there are more subtypes, and agonists vary in specificity between these receptors, and may be classified respectively. However, there are also other mechanisms of adrenergic agonism. Epinephrine and norepinephrine are endogenous and broad-spectrum. More selective agonists are more useful in pharmacology.

<span class="mw-page-title-main">Prazosin</span> Antihypertensive drug

Prazosin, sold under the brand name Minipress among others, is a medication used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is an α1 blocker. It is a less preferred treatment of high blood pressure. Other uses may include heart failure and Raynaud syndrome. It is taken by mouth.

<span class="mw-page-title-main">Ropinirole</span> Dopamine agonist medication

Ropinirole, sold under the brand name Requip among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In PD the dose needs to be adjusted to the effect and treatment should not be suddenly stopped. It is taken by mouth.

<span class="mw-page-title-main">Moxonidine</span> Antihypertensive medication

Moxonidine (INN) is a new-generation alpha-2/imidazoline receptor agonist antihypertensive drug licensed for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors, and calcium channel blockers are not appropriate or have failed to control blood pressure. In addition, it demonstrates favourable effects on parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction. It is also a growth hormone releaser. It is manufactured by Solvay Pharmaceuticals under the brand name Physiotens and Moxon.

<span class="mw-page-title-main">Brimonidine</span> Chemical compound

Brimonidine is an α2 agonist medication used to treat open-angle glaucoma, ocular hypertension, and rosacea. In rosacea it improves the redness. It is used as eye drops or applied to the skin.

The alpha-2 (α2) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α2-adrenergic receptor in the central and peripheral nervous systems.

<span class="mw-page-title-main">Lofexidine</span> Medication used for opioid withdrawal

Lofexidine, sold under the brand name Lucemyra among others, is a medication historically used to treat high blood pressure; today, it is more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an α2A adrenergic receptor agonist. It was approved for use by the Food and Drug Administration in the United States in 2018.

<span class="mw-page-title-main">Gepirone</span> Medication used for major depressive disorder

Gepirone, sold under the brand name Exxua, is a medication used for the treatment of major depressive disorder. It is taken orally.

<span class="mw-page-title-main">Alpha-adrenergic agonist</span> Class of drugs

Alpha-adrenergic agonists are a class of sympathomimetic agents that selectively stimulates alpha adrenergic receptors. The alpha-adrenergic receptor has two subclasses α1 and α2. Alpha 2 receptors are associated with sympatholytic properties. Alpha-adrenergic agonists have the opposite function of alpha blockers. Alpha adrenoreceptor ligands mimic the action of epinephrine and norepinephrine signaling in the heart, smooth muscle and central nervous system, with norepinephrine being the highest affinity. The activation of α1 stimulates the membrane bound enzyme phospholipase C, and activation of α2 inhibits the enzyme adenylate cyclase. Inactivation of adenylate cyclase in turn leads to the inactivation of the secondary messenger cyclic adenosine monophosphate and induces smooth muscle and blood vessel constriction.

A sympatholytic (sympathoplegic) drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder, panic disorder and PTSD. In some cases, such as with guanfacine, they have also shown to be beneficial in the treatment of ADHD.

Imidazoline receptors are the primary receptors on which clonidine and other imidazolines act. There are three main classes of imidazoline receptor: I1 is involved in inhibition of the sympathetic nervous system to lower blood pressure, I2 has as yet uncertain functions but is implicated in several psychiatric conditions, and I3 regulates insulin secretion.

<span class="mw-page-title-main">Fluparoxan</span> Chemical compound

Fluparoxan is a potent α2-adrenergic receptor antagonist with excellent selectivity for this receptor over the α1-adrenergic receptor (2,630-fold), and is the only well-studied α2-adrenergic receptor antagonist in its structural family which does not antagonize any variant of the imidazoline receptor. It was shown to possess central α2-adrenoceptor antagonist activity after oral doses in man and was patented as an antidepressant by Glaxo in the early 1980s, but its development was discontinued when the compound failed to show a clear clinical advantage over existing therapies.

<span class="mw-page-title-main">Tiamenidine</span> Chemical compound

Tiamenidine (BAN, USAN, INN, also known as thiamenidine, Hoe 440) is an imidazoline compound that shares many of the pharmacological properties of clonidine. It is a centrally-acting α2 adrenergic receptor agonist (IC50 = 9.1 nM). It also acts as an α1-adrenergic receptor agonist to a far lesser extent (IC50 = 4.85 μM). In hypertensive volunteers, like clonidine, it significantly increased sinus node recovery time and lowered cardiac output. It was marketed (as tiamenidine hydrochloride) by Sanofi-Aventis under the brand name Sundralen for the management of essential hypertension.

An analgesic adjuvant is a medication that is typically used for indications other than pain control but provides control of pain (analgesia) in some painful diseases. This is often part of multimodal analgesia, where one of the intentions is to minimize the need for opioids.


  1. 1 2 3 4 5 "Zanaflex (tizanidine hydrochloride) Capsules and Tablets for Oral Use. Full Prescribing Information" (PDF). Acorda Therapeutics Inc. Ardsley, NY 10502. Retrieved 1 September 2016.
  2. 1 2 Katzung BG (30 November 2017). Basic & clinical pharmacology (14th ed.). New York: McGraw Hill Education. p. 487. ISBN   9781259641152. OCLC   1015240036.
  3. 1 2 British national formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 1094. ISBN   9780857113382.
  4. 1 2 Kamen L, Henney HR, Runyan JD (February 2008). "A practical overview of tizanidine use for spasticity secondary to multiple sclerosis, stroke, and spinal cord injury". Current Medical Research and Opinion. 24 (2): 425–439. doi:10.1185/030079908X261113. PMID   18167175. S2CID   73086671.
  5. 1 2 3 4 5 "Tizanidine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.
  6. "Tizanidine Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 3 March 2019.
  7. "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  8. "Tizanidine - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  9. "Page not available". PubMed Health. Archived from the original on 11 November 2012. Retrieved 4 September 2017.
  10. Spiller HA, Bosse GM, Adamson LA (January 2004). "Retrospective review of Tizanidine (Zanaflex) overdose". Journal of Toxicology. Clinical Toxicology. 42 (5): 593–596. doi:10.1081/CLT-200026978. PMID   15462150. S2CID   38946270.
  11. "Tizanidine Uses, Dosage, Side Effects – Drugs.com". drugs.com. Retrieved 4 September 2017.
  12. NHS Wales (2011). "Tizanidine (Zanaflex) Gwent Primary Care Prescribing Guidance" (PDF). Aneurin Bevan University Health Board.
  13. "Tizanidine package leaflet: Information for the user" (PDF). Medicines and Healthcare products Regulatory Agency (UK). 2016. Archived from the original (PDF) on 16 September 2018. Retrieved 16 September 2018.
  14. "Zanaflex (tizanidine hydrochloride) dose, indications, adverse effects, interactions... from PDR.net". www.pdr.net. Retrieved 16 September 2018.
  15. 1 2 3 Blaxall HS, Murphy TJ, Baker JC, Ray C, Bylund DB (October 1991). "Characterization of the alpha-2C adrenergic receptor subtype in the opossum kidney and in the OK cell line". The Journal of Pharmacology and Experimental Therapeutics. 259 (1): 323–329. PMID   1656026.
  16. "Tizanidine: MedlinePlus Drug Information". medlineplus.gov. U.S. National Library of Medicine. Retrieved 29 October 2019.
  17. 1 2 USpatent 3843668,Neumann P,"Certain 4-substituted amino-2,1,3-benzothiadiozoles",published 1974-10-22, assigned to Sandoz AG
  18. Pesin VG, Sergeev VA (1969). "Research on 2,1,3-thia- and selenadiazole". Chemistry of Heterocyclic Compounds. 3 (5): 662–666. doi:10.1007/BF00468340. S2CID   98830770.
  19. "Pharmaceutical Substances: Tizanidine". Thieme. Retrieved 16 February 2023.