Tizanidine, sold under the brand name Zanaflex among others, is an alpha-2 (α₂) adrenergic receptor agonist, similar to clonidine, that is used to treat muscle spasticity due to

spinal cord injury A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. It is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Symptoms of ...

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

, and spastic cerebral palsy. Effectiveness appears similar to baclofen or

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. Common side effects of tizanidine include dry mouth, sleepiness, weakness, and

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

. Serious side effects may include low blood pressure, liver problems,

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

, and QT prolongation. It is unclear if use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

and

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

is safe. It is an α₂-adrenergic agonist, but how it works is not entirely clear. Tizanidine was approved for medical use in the United States in 1996. It is available as a generic medication. In 2022, it was the 94th most commonly prescribed medication in the United States, with more than 6million prescriptions.

Medical uses

Tizanidine has been found to be as effective as other antispasmodic drugs and is more tolerable than baclofen and

Side effects

Side effects include dizziness, drowsiness, weakness, nervousness, confusion,

hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

s, 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. Symptoms of

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

in 45 cases reported to a poison control center included: lethargy, bradycardia, hypotension, agitation, confusion, vomiting and coma.

Interactions

Concomitant use of tizanidine and moderate or potent CYP1A2 inhibitors (such as zileuton, certain antiarrhythmics (

amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxys ...

, 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). For this reason both fluvoxamine and tizanidine should not be taken at the same time. Fluoroquinolone antibiotics such as

moxifloxacin Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop. Common side effec ...

, levofloxacin, and

ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin ...

should also be avoided due to an increased serum concentration of tizanidine when administered concomitantly. Tizanidine has the potential to interact with other central nervous system depressants.

Alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

should be avoided, particularly as it can upset the stomach. The CNS-depressant effects of tizanidine and alcohol are additive. Caution with the following interactions: * antibiotics such as enoxacin, gatifloxacin, levofloxacin, lomefloxacin,

ofloxacin Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken Oral administration, by mouth or intravenous, injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prost ...

, sparfloxacin, trovafloxacin, or norfloxacin; * blood pressure medications such as clonidine, guanabenz, guanfacine (Tenex), or methyldopa; * heart rhythm medications such as

(Cordarone, Pacerone), mexiletine (Mexitil), propafenone (Rhythmol), and verapamil (Calan, Covera, Isoptin).

Pharmacology

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.

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. It has a volume of distribution of 2.4 L/kg following intravenous administration.

Chemistry

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

sodium nitrate Sodium nitrate is the chemical compound with the chemical formula, formula . This alkali metal nitrate salt (chemistry), salt is also known as Chile saltpeter (large deposits of which were historically mined in Chile) to distinguish it from ordi ...

sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid (English in the Commonwealth of Nations, Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen, ...

and reduced using iron and acetic acid. : Tizanidine synthesis US3843668

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.

References

{{Authority control Muscle relaxants Alpha-2 adrenergic receptor agonists Imidazolines Drugs developed by Novartis Organochlorides Benzothiadiazoles Wikipedia medicine articles ready to translate