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{{short description|Muscle relaxant medication}}
{{Short description|Muscle relaxant medication}}
⚫
{{Use dmy dates|date=September 2017}}
{{Use American English|date=September 2017}}
{{Use American English|date=September 2017}}
⚫
{{Use dmy dates|date=February 2024}}
{{Drugbox
{{Infobox drug
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 470611127
| verifiedrevid = 470611127
| image = Tizanidine.svg
| image = Tizanidine.svg
| width = 190
| width = 190
| image2 = Tizanidine ball-and-stick.png
| image2 = Tizanidine-from-xtal-3D-bs-17.png


<!-- Clinical data -->
<!-- Clinical data -->
Line 15: Line 15:
| MedlinePlus = a601121
| MedlinePlus = a601121
| DailyMedID = Tizanidine
| DailyMedID = Tizanidine
⚫
| pregnancy_category =
| pregnancy_US = C
⚫
| routes_of_administration = [[Oral administration|By mouth]]
⚫
| pregnancy_category =
⚫
| legal_US = Rx-only
⚫
| routes_of_administration = [[Oral administration|By mouth]] ([[Tablet (pharmacy)|tablets]], [[Capsule (pharmacy)|capsules]])
| ATC_prefix = M03
| ATC_prefix = M03
| ATC_suffix = BX02
| ATC_suffix = BX02
| ATC_supplemental =
| ATC_supplemental =
| class = [[Alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptor agonist]]

⚫
| legal_US = Rx-only


<!-- Pharmacokinetic data -->
<!-- Pharmacokinetic data -->
Line 61: Line 62:


<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Tizanidine''', sold under the brand name '''Zanaflex''' among others, is a medication that is used to treat [[muscle spasticity]] due to [[spinal cord injury]] or [[multiple sclerosis]].<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=1094|edition= 76}}</ref> Effectiveness appears similar to [[baclofen]] or [[diazepam]].<ref name=Kam2008>{{cite journal | vauthors = Kamen L, Henney HR, Runyan JD | title = A practical overview of tizanidine use for spasticity secondary to multiple sclerosis, stroke, and spinal cord injury | journal = Current Medical Research and Opinion | volume = 24 | issue = 2 | pages = 425–39 | date = February 2008 | pmid = 18167175 | doi = 10.1185/030079908X261113 | s2cid = 73086671 }}</ref> It is taken by mouth.<ref name=AHFS2019/>
'''Tizanidine''', sold under the brand name '''Zanaflex''' among others, is an [[Alpha-2 adrenergic receptor|alpha-2 (α<sub>2</sub>) adrenergic receptor]] agonist,<ref name=Katzung/> similar to [[clonidine]], that is used to treat [[muscle spasticity]] due to [[spinal cord injury]], [[multiple sclerosis]], and [[spastic cerebral palsy]].<ref name=BNF76>{{cite book|title=British national formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=1094|edition= 76}}</ref> Effectiveness appears similar to [[baclofen]] or [[diazepam]].<ref name=Kam2008>{{cite journal | vauthors = Kamen L, Henney HR, Runyan JD | title = A practical overview of tizanidine use for spasticity secondary to multiple sclerosis, stroke, and spinal cord injury | journal = Current Medical Research and Opinion | volume = 24 | issue = 2 | pages = 425–439 | date = February 2008 | pmid = 18167175 | doi = 10.1185/030079908X261113 | s2cid = 73086671 }}</ref> It is taken [[by mouth]].<ref name=AHFS2019/>


<!-- Side effects and mechanisms -->
<!-- Side effects and mechanisms -->
Common side effects include dry mouth, sleepiness, weakness, and dizziness.<ref name=AHFS2019/> Serious side effects may include [[low blood pressure]], [[liver problems]], [[psychosis]], and [[QT prolongation]].<ref name=AHFS2019/> It is unclear if use in [[pregnancy]] and [[breastfeeding]] is safe.<ref name=Preg2019>{{cite web |title=Tizanidine Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/tizanidine.html |website=Drugs.com |access-date=3 March 2019 |language=en}}</ref> It is an [[α2-adrenergic agonist]] and how it works is not entirely clear.<ref name=AHFS2019>{{cite web |title=Tizanidine Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/tizanidine-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=3 March 2019 |language=en}}</ref>
Common side effects of tizanidine include [[Xerostomia|dry mouth]], [[Somnolence|sleepiness]], [[weakness]], and [[dizziness]].<ref name=AHFS2019/> Serious side effects may include [[low blood pressure]], [[liver problems]], [[psychosis]], and [[QT prolongation]].<ref name=AHFS2019/> It is unclear if use in [[pregnancy]] and [[breastfeeding]] is safe.<ref name=Preg2019>{{cite web |title=Tizanidine Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/tizanidine.html |website=Drugs.com |access-date=3 March 2019 }}</ref> It is an [[α2-adrenergic agonist|α<sub>2</sub>-adrenergic agonist]], but how it works is not entirely clear.<ref name=AHFS2019>{{cite web |title=Tizanidine Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/tizanidine-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=3 March 2019 }}</ref>


<!-- History and culture -->
<!-- History and culture -->
Tizanidine was approved for medical use in the United States in 1996.<ref name=AHFS2019/> It is available as a [[generic medication]].<ref name=BNF76/> In 2017, it was the 89th most commonly prescribed medication in the United States, with more than nine million prescriptions.<ref>{{cite web |title=The Top 300 of 2020 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=ClinCalc |access-date=11 April 2020}}</ref><ref>{{cite web | title=Tizanidine - Drug Usage Statistics | website=ClinCalc | url=https://clincalc.com/DrugStats/Drugs/Tizanidine | access-date=11 April 2020}}</ref>
Tizanidine was approved for medical use in the United States in 1996.<ref name=AHFS2019/> It is available as a [[generic medication]].<ref name=BNF76/> In 2022, it was the 94th most commonly prescribed medication in the United States, with more than 6{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Tizanidine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Tizanidine | access-date = 30 August 2024 }}</ref>


==Medical uses==
==Medical uses==
⚫
Tizanidine has been found to be as effective as other [[antispasmodic]] drugs and is more tolerable than [[baclofen]] and [[diazepam]].<ref name=Kam2008/>

⚫
Tizanidine has been found to be as effective as other antispasmodic drugs and is more tolerable than [[baclofen]] and [[diazepam]].<ref name=Kam2008/>


== Side effects ==
== Side effects ==
⚫
Side effects include dizziness, drowsiness, weakness, nervousness, confusion, [[hallucination]]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.<ref>{{cite web |url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ |title = Page not available |website = PubMed Health |access-date = 4 September 2017 |url-status = dead |archive-url = https://web.archive.org/web/20121111213511/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ |archive-date = 11 November 2012 |df = dmy-all }}</ref>


Symptoms of [[overdose]] in 45 cases reported to a poison control center included: lethargy, bradycardia, hypotension, agitation, confusion, vomiting and coma.<ref>{{cite journal | vauthors = Spiller HA, Bosse GM, Adamson LA | title = Retrospective review of Tizanidine (Zanaflex) overdose | journal = Journal of Toxicology. Clinical Toxicology | volume = 42 | issue = 5 | pages = 593–596 | date = January 2004 | pmid = 15462150 | doi = 10.1081/CLT-200026978 | s2cid = 38946270 }}</ref>
⚫
Side effects include dizziness, drowsiness, weakness, nervousness, hallucinations, 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.<ref>{{cite web |url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ |title = Page not available |last = pmhdev |website = PubMed Health |access-date = 4 September 2017 |url-status = dead |archive-url = https://web.archive.org/web/20121111213511/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ |archive-date = 11 November 2012 |df = dmy-all }}</ref>


== Interactions ==
== Interactions ==
⚫
[[Concomitant drug|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 contraceptive pill|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 [[Area under curve|AUC]] (plasma drug concentration-time curve).<ref name="Zanaflex PI">{{cite web |title = Zanaflex (tizanidine hydrochloride) Capsules and Tablets for Oral Use. Full Prescribing Information |url = http://www.acorda.com/assets/docs/zanaflexpi-final-fda-approved-subm111813.pdf |publisher = Acorda Therapeutics Inc. Ardsley, NY 10502 |access-date = 1 September 2016 }}</ref> 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.<ref>{{cite web |url = https://www.drugs.com/tizanidine.html |title = Tizanidine Uses, Dosage, Side Effects – Drugs.com |website = drugs.com |access-date = 4 September 2017 }}</ref> Tizanidine has the potential to interact with other [[Central nervous system depression|central nervous system depressants]]. [[alcohol (drug)|Alcohol]] should be avoided, particularly as it can upset the stomach. The CNS-depressant effects of tizanidine and alcohol are additive.<ref name="Zanaflex PI" /> Caution with the following [[Drug interaction|interactions]]:<ref>{{Cite web|url=http://www.wales.nhs.uk/sites3/Documents/814/TIZANIDINE-GwentGuidelines%5BJan08%5D.pdf|title=Tizanidine (Zanaflex) Gwent Primary Care Prescribing Guidance|last=NHS Wales|date=2011|publisher=Aneurin Bevan University Health Board}}</ref><ref>{{Cite web|url=http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1496381982517.pdf|title=Tizanidine package leaflet: Information for the user|date=2016|publisher=Medicines and Healthcare products Regulatory Agency (UK)|access-date=16 September 2018|archive-date=16 September 2018|archive-url=https://web.archive.org/web/20180916202506/http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1496381982517.pdf|url-status=dead}}</ref><ref>{{Cite web|url=http://www.pdr.net/drug-summary/Zanaflex-tizanidine-hydrochloride-811|title=Zanaflex (tizanidine hydrochloride) dose, indications, adverse effects, interactions... from PDR.net|website=www.pdr.net|language=en|access-date=16 September 2018}}</ref>

⚫
[[Concomitant drug|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 contraceptive pill|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 [[Area under curve|AUC]] (plasma drug concentration-time curve).<ref name="Zanaflex PI">{{cite web |title = Zanaflex (tizanidine hydrochloride) Capsules and Tablets for Oral Use. Full Prescribing Information |url = http://www.acorda.com/assets/docs/zanaflexpi-final-fda-approved-subm111813.pdf |publisher = Acorda Therapeutics Inc. Ardsley, NY 10502 |access-date = 1 September 2016 }}</ref> 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.<ref>{{cite web |url = https://www.drugs.com/tizanidine.html |title = Tizanidine Uses, Dosage, Side Effects – Drugs.com |website = drugs.com |access-date = 4 September 2017 }}</ref> Tizanidine has the potential to interact with other [[Central nervous system depression|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.<ref name="Zanaflex PI" /> Caution with the following [[Drug interaction|interactions]]:<ref>{{Cite web|url=http://www.wales.nhs.uk/sites3/Documents/814/TIZANIDINE-GwentGuidelines%5BJan08%5D.pdf|title=Tizanidine (Zanaflex) Gwent Primary Care Prescribing Guidance|last=NHS Wales|date=2011|publisher=Aneurin Bevan University Health Board}}</ref><ref>{{Cite web|url=http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1496381982517.pdf|title=Tizanidine package leaflet: Information for the user |date=2016|publisher=Medicines and Healthcare products Regulatory Agency (UK)}}</ref><ref>{{Cite web|url=http://www.pdr.net/drug-summary/Zanaflex-tizanidine-hydrochloride-811|title=Zanaflex (tizanidine hydrochloride) dose, indications, adverse effects, interactions... from PDR.net|website=www.pdr.net|language=en|access-date=2018-09-16}}</ref>

* antibiotics such as [[enoxacin]], [[gatifloxacin]], [[levofloxacin]], [[lomefloxacin]], [[moxifloxacin]], [[ofloxacin]], [[sparfloxacin]], [[trovafloxacin]], or [[norfloxacin]];
* antibiotics such as [[enoxacin]], [[gatifloxacin]], [[levofloxacin]], [[lomefloxacin]], [[moxifloxacin]], [[ofloxacin]], [[sparfloxacin]], [[trovafloxacin]], or [[norfloxacin]];
* blood pressure medications such as [[clonidine]], [[guanabenz]], [[guanfacine]] (Tenex), or [[methyldopa]];
* blood pressure medications such as [[clonidine]], [[guanabenz]], [[guanfacine]] (Tenex), or [[methyldopa]];
Line 86: Line 85:


== Pharmacology ==
== Pharmacology ==
⚫
Tizanidine is an [[Alpha-2 adrenergic receptor|α<sub>2</sub> 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 α<sub>2</sub> receptor agonism and the spasmolytic action is still not fully understood.<ref name=Katzung>{{Cite book|title=Basic & clinical pharmacology|isbn=9781259641152|edition=14th |location=New York|publisher=McGraw Hill Education|page=487|oclc=1015240036| vauthors = Katzung BG |date = 30 November 2017}}</ref>

{| class="wikitable"
⚫
Tizanidine is an [[Alpha-2 adrenergic receptor|α<sub>2</sub> receptor]] agonist closely related to [[clonidine]]. It has approximately one tenth to one fifteenth of the pressure lowering effect of clonidine. The relation between the α<sub>2</sub> receptor agonism and the spasmolytic action is still not fully understood.<ref>{{Cite book|title=Basic & clinical pharmacology|others=Katzung, Bertram G.|isbn=9781259641152|edition= Fourteenth |location=New York|pages=487|oclc=1015240036|last1 = Katzung|first1 = Bertram G.|date = 30 November 2017}}</ref>
|+
!Site
!''K<sub>i</sub>'' (nM)
!Species
!Ref
|-
|[[Alpha-2A adrenergic receptor|α<sub>2A</sub>]]
|62
|Human
|<ref name=":0" />
|-
|[[Alpha-2B adrenergic receptor|α<sub>2B</sub>]]
|75
|[[OK cells|OK]]
|<ref name=":0" />
|-
|[[Alpha-2C adrenergic receptor|α<sub>2C</sub>]]
|76
|Rat
|<ref name=":0">{{cite journal | vauthors = Blaxall HS, Murphy TJ, Baker JC, Ray C, Bylund DB | title = Characterization of the alpha-2C adrenergic receptor subtype in the opossum kidney and in the OK cell line | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 259 | issue = 1 | pages = 323–329 | date = October 1991 | pmid = 1656026 }}</ref>
|}


===Route of administration===
===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.<ref>{{cite web |title=Tizanidine: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a601121.html |website=medlineplus.gov |publisher=U.S. National Library of Medicine |access-date=29 October 2019 |language=en}}</ref>
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.<ref>{{cite web |title=Tizanidine: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a601121.html |website=medlineplus.gov |publisher=U.S. National Library of Medicine |access-date=29 October 2019 |language=en}}</ref> It has a [[volume of distribution]] of 2.4&nbsp;L/kg following intravenous administration.<ref name="Zanaflex PI" />


===Chemistry===
==Chemistry==
Tizanidine is a derivative of [[2,1,3-Benzothiadiazole|2,1,3-benzothiadiazole]] and its first published synthesis was reported in a patent.<ref name=US3843668>{{cite patent |country=US |number=3843668 |status=patent |pubdate=1974-10-22 |fdate=1973-05-08 |pridate=1972-05-09 |invent1 = Neumann P |title=Certain 4-substituted amino-2,1,3-benzothiadiozoles |assign1=Sandoz AG }}</ref> The 5-chloro-2,1,3-benzothiadiazol-4-amine intermediate was a known compound, produced in three steps from 4-chlorophenylenediamine as shown.<ref name="Pesin1" >{{cite journal |doi=10.1007/BF00468340 |title=Research on 2,1,3-thia- and selenadiazole |year=1969 | vauthors = Pesin VG, Sergeev VA |journal=Chemistry of Heterocyclic Compounds |volume=3 |issue=5 |pages=662–666 |s2cid=98830770 }}</ref> Treatment with two equivalents of [[thionyl chloride]] in [[pyridine]] formed the [[heterocycle]], which was [[nitration|nitrated]] with [[sodium nitrate]] in [[sulfuric acid]] and [[redox|reduced]] using iron and acetic acid.
It has a [[volume of distribution]] of 2.4 L/kg following intravenous administration.<ref name="Zanaflex PI" />
:[[File:Tizanidine synthesis US3843668.svg|620px]]
{{-}}
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.<ref name=US3843668/><ref>{{cite web |url=https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-20-0115 |title=Pharmaceutical Substances: Tizanidine |publisher=Thieme |access-date=16 February 2023}}</ref>


== References ==
== References ==
{{reflist}}
{{reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/tizanidine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Tizanidine }}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/tizanidine%20hydrochloride | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Tizanidine hydrochloride }}
* {{cite web | url =https://tizanidine-side-effects.us/ | publisher = tizanidine-side-effects.us | work = Drug Information Portal | title =
Tizanidine side effects }}


{{Muscle relaxants}}
{{Muscle relaxants}}
{{Adrenergic agonists}}
{{Adrenergic receptor modulators}}

{{Portal bar | Medicine}}
{{Portal bar | Medicine}}
{{Authority control}}
{{Authority control}}


[[Category:Muscle relaxants]]
[[Category:Muscle relaxants]]
[[Category:Alpha-adrenergic agonists]]
[[Category:Alpha-2 adrenergic receptor agonists]]
[[Category:Imidazolines]]
[[Category:Imidazolines]]
[[Category:Novartis brands]]
[[Category:Drugs developed by Novartis]]
[[Category:Organochlorides]]
[[Category:Organochlorides]]
[[Category:Benzothiadiazoles]]
[[Category:Benzothiadiazoles]]

Latest revision as of 19:05, 27 November 2024

Tizanidine
Clinical data
Pronunciation/taɪˈzænɪdiːn/ tye-ZAN-i-deen
Trade namesZanaflex, 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.comMonograph
MedlinePlusa601121
License data
Routes of
administration		By mouth
Drug classα2-adrenergic receptor agonist
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability~40%[1]
Protein binding~30%
MetabolismLiver (CYP1A2, 95%)
Elimination half-life2.54 hours (tizanidine), 20–40 hours (inactive metabolites)[1]
ExcretionUrine (60%), feces (20%)
Identifiers
  • 5-Chloro-N-(4,5-dihydro-1H-imidazol-2-yl)benzo[c] [1,2,5]thiadiazol-4-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.125.400 Edit this at Wikidata
Chemical and physical data
FormulaC9H8ClN5S
Molar mass253.71 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) checkY
  • Key:XFYDIVBRZNQMJC-UHFFFAOYSA-N checkY
  (verify)

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 2022, it was the 94th most commonly prescribed medication in the United States, with more than 6 million prescriptions.[7][8]

Medical uses

[edit]

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

Side effects

[edit]

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]

Interactions

[edit]

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]

Pharmacology

[edit]

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]

Site Ki (nM) Species Ref
α2A 62 Human [15]
α2B 75 OK [15]
α2C 76 Rat [15]

Route of administration

[edit]

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]

Chemistry

[edit]

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.

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]

References

[edit]
  1. ^ a b c d e "Zanaflex (tizanidine hydrochloride) Capsules and Tablets for Oral Use. Full Prescribing Information" (PDF). Acorda Therapeutics Inc. Ardsley, NY 10502. Retrieved 1 September 2016.
  2. ^ a b Katzung BG (30 November 2017). Basic & clinical pharmacology (14th ed.). New York: McGraw Hill Education. p. 487. ISBN 9781259641152. OCLC 1015240036.
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