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Tizanidine

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Tizanidine can induce dangerously low blood pressures when used in excessive doses [1] [2]

Care should be taken when taking high doses of tizanidine, even with an established tolerance. Users taking hallucinogenic doses should have a hypertensive agent available[3] or a supervisor present. Exercise extreme caution when attempting hallucinogenic doses.

Summary sheet: Tizanidine


Tizanidine (known by the trade names Zanaflex and Trinex among others) is a depressant substance of the 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 [4].

Tizanidine
Chemical Nomenclature
Common names Tizanidine, Xanaflex, Sirdalud, Trinex
Substitutive name 2,1,3-Benzothiadiazole
Systematic name 5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine
Class Membership
Psychoactive class Depressant
Chemical class Arylaminoimidazoline
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



⇣ Oral
Dosage
Threshold 25 μg
Light 2 - 3 mg
Common 4 - 5 mg
Strong 6 - 8 mg
Heavy 8 mg +
Duration
Total 2 - 6 hours
Onset 15 - 45 minutes
Peak 60 - 120 minutes









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Interactions
Stimulants
Depressants
Dissociatives

Tizanidine is a central α2 adrenergic agonist. The relationship between the α2 receptor agonism and the spasmolytic function of tizanidine is not fully understood [5] .

While recreational use is extremely rare, some users take tizanidine for its standalone sedative effects or to potentiate the effects of opiates [6] [7] [8] [9] [10] [11] . In higher doses, tizanidine is capable of inducing hallucinations, psychosis, and delirium [12] [13] [14] [15].

Chemistry

Tizanidine is 2,1,3-Benzothiadiazole substituted at C-4 by a Delta(1)-imidazolin-2-ylamino group and at C-4 by a chloro group. It is an agonist at α2-adrenergic receptor sites. It is a benzothiadiazole and a member of imidazoles[16].

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 [17].

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[18]. Tizanidine has approximately one tenth to one fifteenth of the blood pressure lowering effect of clonidine [19] .

Tizanidine has also been found to have anticonvulsant effects against strychnine-induced seizures but not against GABA-induced seizures. The α2 receptor mediated inhibition of inter-neuronal activity appears to be the cause of Tizanidine's anti-convulsant properties [20] [21].

Tizanidine has an oral bioavailability of 20-34% and an elimination half-life of 2.5 hours. It attains steady-state concentration within 24-48 hours after administration [22]

The table below compares the selectivity of Tizanidine and other drugs to the imidzaoline-receptor and the α2 receptors in rats. Tizanidine has a significantly greater selectivity to the imidazoline receptor than clonidine. The imidazoline receptor selectivity of tizanidine may be responsible for its unique pharmacological profile[23].

Drug Imidazoline receptors Ki (nM) α2 Receptors Ki (nM)
Tizanidine 4.17 ± 1.81 91.5 ± 9.1
Clonidine 9.20 ± 1.23 9.20 ± 1.23
Oxymethazoline 2.28 ± 0.36 25.9 ± 5.5
Naphazoline 309 ± 26 25.9 ± 5.5
Adrenaline > 10000 3.18 ± 0.41

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects
 

Visual effects
 

  • Distortions

    Geometry

    At high doses, geometry can be observed likely due to experiencing low blood pressure and circulation to the brain. The geometry is distinct from psychedelic and dissociative drugs. It can be described as intricate in complexity, abstract in form, synthetic in feel, unstructured in organization, dimly lit, multicolored in scheme, flat in shading, soft in edges, smooth in motion, slow in speed, small in size, angular in corners, non-immersive in depth, and consistent in intensity.

    The geometry of Tizanidine never exceeds level 4. The doses required to observe such geometries can induce dangerously low blood pressures and cause one to lose consciousness [24]. Users should exercise caution when taking hallucinogenic doses, as the threshold for hallucinations is not far from the threshold for psychosis in many users [25].

    Hallucinatory states

    In higher doses, Tizanidine is capable of inducing a delirious state.

Cognitive effects
 

After effects
 

    • Increased heart rate - This occurs as a rebound effect to tizanidine's cardiovascular effects and typically presents itself after prolonged use.
    • Increased blood pressure - This occurs as a rebound effect to tizanidine's cardiovascular effects and typically presents itself after prolonged use.
    • Irritability
    • Soreness - After the effects of tizanidine wear off, muscles that weren't sore before using the drug can become sore with more ease. For most users, this first presents itself as an increased soreness in the neck.

Experience reports

There are currently 0 experience reports which describe the effects of this substance in our experience index.

Additional experience reports can be found here:

Toxicity and harm potential

 

This toxicity and harm potential section is a stub.

As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it.
Note: Always conduct independent research and use harm reduction practices if using this substance.

It is strongly recommended that one use harm reduction practices when using this substance.

While no long term studies of tizanidine use in humans have been done, studies done in animals indicate no signs of long term carcinogenicity. However, tizanidine has been shown to have a developmental effect on young rats[26].

Some long term tizanidine use has been attributed to liver problems and in extreme cases, liver failure and death[27].

Lethal dosage

The LD50 of oral tizanidine in rats was found to be 414mg/kg in rats and 235 mg/kg in mice[28].

In some cases, Tizanidine overdose can be reversed with naloxone; however, this is not the case with everyone [29] [30].

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[31].

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

  • Depressants (1,4-Butanediol, 2M2B, alcohol, benzodiazepines, barbiturates, GHB/GBL, methaqualone, opioids) - This combination potentiates the muscle relaxation, amnesia, sedation, and respiratory depression caused by one another. At higher doses, it can lead to a sudden, unexpected loss of consciousness along with a dangerous amount of depressed respiration. There is also an increased risk of suffocating on one's vomit while unconscious. If nausea or vomiting occurs before a loss of consciousness, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Dissociatives - This combination can unpredictably potentiate the amnesia, sedation, motor control loss and delusions that can be caused by each other. It may also result in a sudden loss of consciousness accompanied by a dangerous degree of respiratory depression. If nausea or vomiting occurs before consciousness is lost, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Stimulants - Stimulants mask the sedative effect of depressants, which is the main factor most people use to gauge their level of intoxication. Once the stimulant effects wear off, the effects of the depressant will significantly increase, leading to intensified disinhibition, motor control loss, and dangerous black-out states. This combination can also potentially result in severe dehydration if one's fluid intake is not closely monitored. If choosing to combine these substances, one should strictly limit themselves to a pre-set schedule of dosing only a certain amount per hour until a maximum threshold has been reached.
 

This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

  • 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.

See also

References

  1. ↑ Johnson TR, Tobias JD. Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension. J Child Neurol. 2000 Dec;15(12):818-9. doi: 10.1177/088307380001501211. PMID: 11198499.
  2. ↑ Chaugai S, Dickson AL, Shuey MM, Feng Q, Barker KA, Wei WQ, Luther JM, Stein CM, Chung CP. Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated Hypotension: A Retrospective Cohort Study. Clin Pharmacol Ther. 2019 Mar;105(3):703-709. doi: 10.1002/cpt.1233. Epub 2018 Oct 18. PMID: 30223305; PMCID: PMC6379114.
  3. ↑ Sharma S, Hashmi MF, Bhattacharya PT. Hypotension. [Updated 2022 Feb 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
  4. ↑ 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.
  5. ↑ Katzung, Bertram G. (30 November 2017). Basic & clinical pharmacology. Katzung, Bertram G. (Fourteenth ed.). New York. p. 487. ISBN 9781259641152. OCLC 1015240036
  6. ↑ FDA. (2013, October 4) Highlights of Prescribing Information. ZANAFLEX. Retrieved https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021447s011_020397s026lbl.pdf
  7. ↑ DrugsDetails. (n.d.). Tizanidine recreational use. from https://drugsdetails.com/tizanidine-recreational-use/
  8. ↑ Healthline. (n.d.). Tizanidine: Side Effects, Dosage, Uses, and More. from https://www.healthline.com/health/tizanidine-oral-tablet
  9. ↑ MedlinePlus.gov. (n.d.). Tizanidine: MedlinePlus Drug Information. from https://medlineplus.gov/druginfo/meds/a601121.html
  10. ↑ 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
  11. ↑ 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
  12. ↑ pmhdev. Tizanidine. PubMed Health. Archived from the original on 11 November 2012.
  13. ↑ 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
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ National Center for Biotechnology Information. "PubChem Compound Summary for CID 5487, Tizanidine" PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Tizanidine.
  17. ↑ 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/
  18. ↑ 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/
  19. ↑ Katzung, Bertram G. (30 November 2017). Basic & clinical pharmacology. Katzung, Bertram G. (Fourteenth ed.). New York. p. 487. ISBN 9781259641152. OCLC 1015240036
  20. ↑ Denizbaşi A, Berkman K, Ozyazgan S, Eşkazan E. The effect of tizanidine on maximal electroshock seizures (MES) in mice. Gen Pharmacol. 1999 Apr;32(4):513-6. doi: 10.1016/s0306-3623(98)00249-3. Erratum in: Gen Pharmacol 2000 Jun;34(6):443. PMID: 10323494.
  21. ↑ Amabeoku G, Chandomba R. Strychnine-induced seizures in mice: the role of noradrenaline. Prog Neuropsychopharmacol Biol Psychiatry. 1994 Jul;18(4):753-63. doi: 10.1016/0278-5846(94)90082-5. PMID: 7938564.
  22. ↑ 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/
  23. ↑ Muramatsu I, Kigoshi S. Tizanidine may discriminate between imidazoline-receptors and alpha 2-adrenoceptors. Jpn J Pharmacol. 1992 Aug;59(4):457-9. doi: 10.1254/jjp.59.457. PMID: 1331591.. Retrieved from https://pubmed.ncbi.nlm.nih.gov/1331591/
  24. ↑ Miyakawa T, Shikai I. Hallucinatory and delusional states in connection with blood pressure and EEG. Folia Psychiatr Neurol Jpn. 1979;33(1):9-13. doi: 10.1111/j.1440-1819.1979.tb00168.x. PMID: 456959.
  25. ↑ 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/
  26. ↑ https://www.drugbank.ca/drugs/DB00697
  27. ↑ Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Tizanidine. [Updated 2017 Jan 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548048/
  28. ↑ https://www.drugbank.ca/drugs/DB00697
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ "Tizanidine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.
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