Tizanidine: Difference between revisions

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'''Tizanidine''' (known by the trade names '''Zanaflex''' and '''Trinex''' among others) is a [[depressant]] substance of the ~~imidazoline~~ class closely related to [[clonidine]]. Tizanidine is primarily used primarily as an antispasmodic drug. Tizanidine's effectivness is similar to that of [[baclofen]] or [[diazepam]] <ref> Wagstaff AJ, Bryson HM. Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435-52. doi: 10.2165/00003495-199753030-00007. PMID: 9074844. </ref>.

'''Tizanidine''' (known by the trade names '''Zanaflex''' and '''Trinex''' among others) is a [[depressant]] substance of the [[chemical class::arylaminoimidazoline]] class closely related to [[clonidine]]. Tizanidine is primarily used primarily as an antispasmodic drug. Tizanidine's effectivness is similar to that of [[baclofen]] or [[diazepam]] <ref> Wagstaff AJ, Bryson HM. Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435-52. doi: 10.2165/00003495-199753030-00007. PMID: 9074844. </ref>.

Tizanidine is a central α2 adrenergic agonist. The relationship between the α2 receptor agonism and the spasmolytic function of tizanidine is not fully understood <ref> Katzung, Bertram G. (30 November 2017). Basic & clinical pharmacology. Katzung, Bertram G. (Fourteenth ed.). New York. p. 487. ISBN 9781259641152. OCLC 1015240036 </ref> .

While recreational use is extremely rare, some users take tizanidine for its standalone sedative effects or to potentiate the effects of [[opiates]]. In higher doses, tizanidine is capable of inducing [[hallucinations]], [[psychosis]], and [[delirium]] <ref> pmhdev. [https://web.archive.org/web/20121111213511/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ Tizanidine]. PubMed Health. Archived from [https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ the original] on 11 November 2012. </ref>.

While recreational use is extremely rare, some users take tizanidine for its standalone sedative effects or to potentiate the effects of [[opiates]] <ref> FDA. (2013, October 4) Highlights of Prescribing Information. ZANAFLEX. Retrieved https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021447s011_020397s026lbl.pdf </ref> <ref> DrugsDetails. (n.d.). Tizanidine recreational use. from https://drugsdetails.com/tizanidine-recreational-use/ </ref> <ref> Healthline. (n.d.). Tizanidine: Side Effects, Dosage, Uses, and More. from https://www.healthline.com/health/tizanidine-oral-tablet </ref> <ref> MedlinePlus.gov. (n.d.). Tizanidine: MedlinePlus Drug Information. from https://medlineplus.gov/druginfo/meds/a601121.html </ref> <ref> WebMD. (n.d.). MS Muscle Spasticity: How To Manage Muscle Spasms & Tightness. from https://www.webmd.com/multiple-sclerosis/controlling-muscle-spasms-multiple-sclerosis#1 </ref> <ref> National Institute on Drug Abuse. (2020, June 16). The Science of Drug Use: Discussion Points. from https://www.drugabuse.gov/drug-topics/criminal-justice/science-drug-use-discussion-points </ref> . In higher doses, tizanidine is capable of inducing [[hallucinations]], [[psychosis]], and [[delirium]] <ref> pmhdev. [https://web.archive.org/web/20121111213511/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ Tizanidine]. PubMed Health. Archived from [https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ the original] on 11 November 2012. </ref> <ref> Suárez-Lledó A, Padullés A, Lozano T, Cobo-Sacristán S, Colls M, Jódar R. Management of Tizanidine Withdrawal Syndrome: A Case Report. Clin Med Insights Case Rep. 2018;11:1179547618758022. Published 2018 Feb 13. doi:10.1177/1179547618758022 </ref> <ref> Karol DE, Muzyk AJ, Preud'homme XA. A case of delirium, motor disturbances, and autonomic dysfunction due to baclofen and tizanidine withdrawal: a review of the literature. Gen Hosp Psychiatry. 2011 Jan-Feb;33(1):84.e1-2. doi: 10.1016/j.genhosppsych.2010.10.003. Epub 2010 Nov 13. PMID: 21353141. </ref> <ref> Fick, Donna, et al. "American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults."

Journal of the American Geriatrics Society 60.4 (2012): 616-631. </ref>.

==Chemistry==

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==Pharmacology==

Tizanidine is an [[imidazoline]] derivative and centrally acting α2 [[adrenergic]] [[agonist]] closely related to Clonidine. Tizanidine inhibits the release of excitatory amino acids from spinal interneurons. As a result, Tizanidine enhances the presynaptic inhibition of motor neurons.

Tizanidine is an [[imidazoline]] derivative and centrally acting α2 [[adrenergic]] [[agonist]] closely related to Clonidine. Tizanidine inhibits the release of excitatory amino acids from spinal interneurons. As a result, Tizanidine enhances the presynaptic inhibition of motor neurons <ref> Ghanavatian S, Derian A. Tizanidine. [Updated 2021 Aug 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519505/ </ref>.

Tizanidine also has some affinity for the α1 receptors, but to a lesser than Clonidine, which may explain why its cardiovascular effects are so much milder than that of Clonidine<ref> Ghanavatian S, Derian A. Tizanidine. [Updated 2021 Aug 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519505/ </ref>. Tizanidine has approximately one tenth to one fifteenth of the blood pressure lowering effect of clonidine <ref> Katzung, Bertram G. (30 November 2017). Basic & clinical pharmacology. Katzung, Bertram G. (Fourteenth ed.). New York. p. 487. ISBN 9781259641152. OCLC 1015240036 </ref> .

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*'''[[Effect::Muscle relaxation]]'''

*'''[[Effect::Physical euphoria]]''' - This effect is very mild and may not be pronounced at all in some users.

*'''[[Effect::~~Lip numbing~~]]''' - ~~Numbing of the lips~~ only occurs at higher doses as a result of low blood pressure.

*'''[[Effect::Spontaneous bodily sensations]]''' - It only occurs at higher doses as a result of low blood pressure and mostly at lips.

*'''[[Effect::Perception of bodily heaviness]]'''

*'''[[Effect::Decreased blood pressure]]'''

*'''[[Effect::Decreased heart rate]]'''

*'''[[Effect::Abnormal heartbeat]]'''

*'''[[Effect::Dizziness]]''' - Because of the cardiovascular effects of ~~tizanidine~~, users can become dizzy or lightheaded.

*'''[[Effect::Dizziness]]''' - Because of the cardiovascular effects of Tizanidine, users can become dizzy or lightheaded.

*'''[[Effect::Headache]]''' - When taking excessive doses, headaches are a common side effect.

*'''[[Effect::Watery eyes]]'''

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*'''[[Effect::Pupil constriction]]'''

*'''[[Effect::Dry mouth]]'''

}}

{{effects/visual|

*'''[[Effect::Acuity suppression]]''' - This effect typically presents itself at higher doses.

*'''[[Effect::~~Blurred vision~~]]''' - This effect typically presents itself at higher doses.

*'''[[Effect::Acuity suppression]]'''

====Distortions====

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*'''[[Effect::Scenarios and plots]]'''

}}

|{{effects/cognitive|

*'''[[Effect::Cognitive fatigue]]'''

*'''[[Effect::Dream potentiation]]''' - Some users of tizanidine notice strange or increasingly vivid dreams after continuous use of tizanidine.

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*'''[[Effect::Delirium]]''' - At extremely high doses, delirium can be induced.

*'''[[Effect::Sleepiness]]''' - This is the most prevalent cognitive effect of Tizanidine

}}

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===Lethal dosage===

The [[LD50]] of oral tizanidine in rats was found to be 414mg/kg in rats and 235 mg/kg in mice<ref> https://www.drugbank.ca/drugs/DB00697 </ref>.

In some cases, Tizanidine overdose can be reversed with naloxone; however, this is not the case with everyone <ref> Bader D, Adam A, Shaban M, Alyahya B. Pediatric tizanidine toxicity reversed with naloxone: a case report. Int J Emerg Med. 2021 Dec 14;14(1):73. doi: 10.1186/s12245-021-00397-y. PMID: 34906071; PMCID: PMC8903539. </ref> <ref> Spiller HA, Bosse GM, Adamson LA. Retrospective review of Tizanidine (Zanaflex) overdose. J Toxicol Clin Toxicol. 2004;42(5):593-6. doi: 10.1081/clt-200026978. PMID: 15462150. </ref>.

===Tolerance and addiction potential===

While dependence is rare, use of Tizanidine exceeding 36mg daily over an extended period of time can lead to hypertensive withdrawals. In cases where dependence has been built, a user should taper to avoid a hypertensive crisis<ref> "Tizanidine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019. </ref>.

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==Legal status==

* '''Austria:''' Tizanidine is available by prescription only.

* '''Turkey:''' Tizanidine is available in pharmacies without prescription.

* '''United States:''' Tizanidine is available by prescription only.

* '''United Kingdom:''' Tizanidine is available by prescription only.

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==External links==

* [https://en.wikipedia.org/wiki/Tizanidine (Wikipedia)]

*[https://en.wikipedia.org/wiki/Tizanidine Tizanidine (Wikipedia)]

* [https://erowid.org/experiences/subs/exp_Tizanidine.shtml Tizanidine (Erowid Vault)]

*[https://isomerdesign.com/pihkal/explore/15021 Tizanidine (IsomerDesign)]

* [https://~~druginfo.nlm~~.~~nih~~.~~gov~~/~~drugportal~~/~~name/tizanidine "~~Tizanidine"]~~. Drug Information Portal. U.S. National Library of Medicine.~~

*[https://erowid.org/experiences/subs/exp_Tizanidine.shtml Tizanidine (Erowid Vault)]

*[https://go.drugbank.com/drugs/DB00697 Tizanidine (DrugBank)]

==References==

[[Category:Psychoactive substance]][[Category:~~Proofread~~]][[Category:~~Approval~~]]

[[Category:Psychoactive substance]]

[[Category:Arylaminoimidazoline]]

[[Category:Depressant]]

@@ Line 3: / Line 3: @@
 {{SubstanceBox/Tizanidine}}
-'''Tizanidine''' (known by the trade names '''Zanaflex''' and '''Trinex''' among others) is a [[depressant]] substance of the imidazoline class closely related to [[clonidine]]. Tizanidine is primarily used primarily as an antispasmodic drug. Tizanidine's effectivness is similar to that of [[baclofen]] or [[diazepam]] <ref> Wagstaff AJ, Bryson HM. Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435-52. doi: 10.2165/00003495-199753030-00007. PMID: 9074844. </ref>.
+'''Tizanidine''' (known by the trade names '''Zanaflex''' and '''Trinex''' among others) is a [[depressant]] substance of the [[chemical class::arylaminoimidazoline]] class closely related to [[clonidine]]. Tizanidine is primarily used primarily as an antispasmodic drug. Tizanidine's effectivness is similar to that of [[baclofen]] or [[diazepam]] <ref> Wagstaff AJ, Bryson HM. Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435-52. doi: 10.2165/00003495-199753030-00007. PMID: 9074844. </ref>.
 Tizanidine is a central α<sub>2</sub> adrenergic agonist. The relationship between the α<sub>2</sub> receptor agonism and the spasmolytic function of tizanidine is not fully understood <ref> Katzung, Bertram G. (30 November 2017). Basic & clinical pharmacology. Katzung, Bertram G. (Fourteenth ed.). New York. p. 487. ISBN 9781259641152. OCLC 1015240036 </ref> .
-While recreational use is extremely rare, some users take tizanidine for its standalone sedative effects or to potentiate the effects of [[opiates]]. In higher doses, tizanidine is capable of inducing [[hallucinations]], [[psychosis]], and [[delirium]] <ref>  pmhdev. [https://web.archive.org/web/20121111213511/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ Tizanidine]. PubMed Health. Archived from [https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ the original] on 11 November 2012. </ref>.
+While recreational use is extremely rare, some users take tizanidine for its standalone sedative effects or to potentiate the effects of [[opiates]] <ref> FDA. (2013, October 4) Highlights of Prescribing Information. ZANAFLEX. Retrieved https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021447s011_020397s026lbl.pdf  </ref> <ref> DrugsDetails. (n.d.). Tizanidine recreational use. from https://drugsdetails.com/tizanidine-recreational-use/ </ref> <ref> Healthline. (n.d.). Tizanidine: Side Effects, Dosage, Uses, and More. from https://www.healthline.com/health/tizanidine-oral-tablet </ref> <ref> MedlinePlus.gov. (n.d.). Tizanidine: MedlinePlus Drug Information. from https://medlineplus.gov/druginfo/meds/a601121.html </ref> <ref> WebMD. (n.d.). MS Muscle Spasticity: How To Manage Muscle Spasms & Tightness. from https://www.webmd.com/multiple-sclerosis/controlling-muscle-spasms-multiple-sclerosis#1 </ref> <ref> National Institute on Drug Abuse. (2020, June 16). The Science of Drug Use: Discussion Points. from https://www.drugabuse.gov/drug-topics/criminal-justice/science-drug-use-discussion-points </ref> . In higher doses, tizanidine is capable of inducing [[hallucinations]], [[psychosis]], and [[delirium]] <ref>  pmhdev. [https://web.archive.org/web/20121111213511/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ Tizanidine]. PubMed Health. Archived from [https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000106/ the original] on 11 November 2012. </ref> <ref> Suárez-Lledó A, Padullés A, Lozano T, Cobo-Sacristán S, Colls M, Jódar R. Management of Tizanidine Withdrawal Syndrome: A Case Report. Clin Med Insights Case Rep. 2018;11:1179547618758022. Published 2018 Feb 13. doi:10.1177/1179547618758022 </ref> <ref> Karol DE, Muzyk AJ, Preud'homme XA. A case of delirium, motor disturbances, and autonomic dysfunction due to baclofen and tizanidine withdrawal: a review of the literature. Gen Hosp Psychiatry. 2011 Jan-Feb;33(1):84.e1-2. doi: 10.1016/j.genhosppsych.2010.10.003. Epub 2010 Nov 13. PMID: 21353141. </ref> <ref> Fick, Donna, et al. "American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults."
+Journal of the American Geriatrics Society 60.4 (2012): 616-631. </ref>.
 ==Chemistry==
@@ Line 13: / Line 14: @@
 ==Pharmacology==
-Tizanidine is an [[imidazoline]] derivative and centrally acting α<sub>2</sub> [[adrenergic]] [[agonist]] closely related to Clonidine. Tizanidine inhibits the release of excitatory amino acids from spinal interneurons. As a result, Tizanidine enhances the presynaptic inhibition of motor neurons.
+Tizanidine is an [[imidazoline]] derivative and centrally acting α<sub>2</sub> [[adrenergic]] [[agonist]] closely related to Clonidine. Tizanidine inhibits the release of excitatory amino acids from spinal interneurons. As a result, Tizanidine enhances the presynaptic inhibition of motor neurons <ref> Ghanavatian S, Derian A. Tizanidine. [Updated 2021 Aug 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519505/ </ref>.
 Tizanidine also has some affinity for the α<sub>1</sub> receptors, but to a lesser than Clonidine, which may explain why its cardiovascular effects are so much milder than that of Clonidine<ref> Ghanavatian S, Derian A. Tizanidine. [Updated 2021 Aug 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519505/ </ref>. Tizanidine has approximately one tenth to one fifteenth of the blood pressure lowering effect of clonidine <ref> Katzung, Bertram G. (30 November 2017). Basic & clinical pharmacology. Katzung, Bertram G. (Fourteenth ed.). New York. p. 487. ISBN 9781259641152. OCLC 1015240036 </ref> .
@@ Line 63: / Line 64: @@
 *'''[[Effect::Muscle relaxation]]'''
 *'''[[Effect::Physical euphoria]]''' - This effect is very mild and may not be pronounced at all in some users.
-*'''[[Effect::Lip numbing]]''' - Numbing of the lips only occurs at higher doses as a result of low blood pressure.
+*'''[[Effect::Spontaneous bodily sensations]]''' - It only occurs at higher doses as a result of low blood pressure and mostly at lips.
 *'''[[Effect::Perception of bodily heaviness]]'''
 *'''[[Effect::Decreased blood pressure]]'''
 *'''[[Effect::Decreased heart rate]]'''
 *'''[[Effect::Abnormal heartbeat]]'''
-*'''[[Effect::Dizziness]]''' - Because of the cardiovascular effects of tizanidine, users can become dizzy or lightheaded.
+*'''[[Effect::Dizziness]]''' - Because of the cardiovascular effects of Tizanidine, users can become dizzy or lightheaded.
 *'''[[Effect::Headache]]''' - When taking excessive doses, headaches are a common side effect.
 *'''[[Effect::Watery eyes]]'''
@@ Line 74: / Line 75: @@
 *'''[[Effect::Pupil constriction]]'''
 *'''[[Effect::Dry mouth]]'''
+}}
-}}
 {{effects/visual|
+*'''[[Effect::Acuity suppression]]''' - This effect typically presents itself at higher doses.
-*'''[[Effect::Blurred vision]]''' - This effect typically presents itself at higher doses.
-*'''[[Effect::Acuity suppression]]'''
 ====Distortions====
@@ Line 97: / Line 94: @@
 *'''[[Effect::Scenarios and plots]]'''
 }}
 |{{effects/cognitive|
 *'''[[Effect::Cognitive fatigue]]'''
 *'''[[Effect::Dream potentiation]]''' - Some users of tizanidine notice strange or increasingly vivid dreams after continuous use of tizanidine.
@@ Line 110: / Line 105: @@
 *'''[[Effect::Delirium]]''' - At extremely high doses, delirium can be induced.
 *'''[[Effect::Sleepiness]]''' - This is the most prevalent cognitive effect of Tizanidine
 }}
@@ Line 136: / Line 130: @@
 ===Lethal dosage===
 The [[LD50]] of oral tizanidine in rats was found to be 414mg/kg in rats and 235 mg/kg in mice<ref> https://www.drugbank.ca/drugs/DB00697 </ref>.
+In some cases, Tizanidine overdose can be reversed with naloxone; however, this is not the case with everyone <ref> Bader D, Adam A, Shaban M, Alyahya B. Pediatric tizanidine toxicity reversed with naloxone: a case report. Int J Emerg Med. 2021 Dec 14;14(1):73. doi: 10.1186/s12245-021-00397-y. PMID: 34906071; PMCID: PMC8903539. </ref> <ref> Spiller HA, Bosse GM, Adamson LA. Retrospective review of Tizanidine (Zanaflex) overdose. J Toxicol Clin Toxicol. 2004;42(5):593-6. doi: 10.1081/clt-200026978. PMID: 15462150. </ref>.
 ===Tolerance and addiction potential===
 While dependence is rare, use of Tizanidine exceeding 36mg daily over an extended period of time can lead to hypertensive withdrawals. In cases where dependence has been built, a user should taper to avoid a hypertensive crisis<ref> "Tizanidine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019. </ref>.
@@ Line 144: / Line 141: @@
 ==Legal status==
 {{LegalStub}}
+* '''Austria:''' Tizanidine is available by prescription only.
+* '''Turkey:''' Tizanidine is available in pharmacies without prescription.
 * '''United States:''' Tizanidine is available by prescription only.
 * '''United Kingdom:''' Tizanidine is available by prescription only.
@@ Line 155: / Line 154: @@
 ==External links==
-* [https://en.wikipedia.org/wiki/Tizanidine (Wikipedia)]
+*[https://en.wikipedia.org/wiki/Tizanidine Tizanidine (Wikipedia)]
-* [https://erowid.org/experiences/subs/exp_Tizanidine.shtml Tizanidine (Erowid Vault)]
+*[https://isomerdesign.com/pihkal/explore/15021 Tizanidine (IsomerDesign)]
-* [https://druginfo.nlm.nih.gov/drugportal/name/tizanidine "Tizanidine"]. Drug Information Portal. U.S. National Library of Medicine.
+*[https://erowid.org/experiences/subs/exp_Tizanidine.shtml Tizanidine (Erowid Vault)]
+*[https://go.drugbank.com/drugs/DB00697 Tizanidine (DrugBank)]
 ==References==
 <references />
-[[Category:Psychoactive substance]][[Category:Proofread]][[Category:Approval]]
+[[Category:Psychoactive substance]]
+[[Category:Arylaminoimidazoline]]
+[[Category:Depressant]]