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Tizanidine

  • David A. Gelber
Chapter
Part of the Current Clinical Neurology book series (CCNEU)

Abstract

Spasticity develops as a consequence of central nervous system (CNS) lesions that affect descending tracts in the brain and spinal cord that normally inhibit spinal-reflex pathways (1). This results in a velocity-dependent increase in muscle tone (spasticity) and is often accompanied by an increase in muscle-stretch reflexes, abnormal cutaneous and autonomic reflexes, muscle weakness, poor dexterity, painful spasms, and co-contraction of agonist and antagonist muscles (2,3). Treatment of spasticity is generally considered when it results in pain, or interferes with functional activities, such as ambulation, transfers, posture, and hygiene (4,5). Medications, such as tizanidine, are often used to manage spasticity, when more conservative interventions, such as nursing cares, physical therapy, splints, and orthoses have been ineffective (6).

Keywords

Multiple Sclerosis Muscle Spasm Spinal Cord Injury Patient Dantrolene Sodium British Medical Research Council 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Gelber, D. A. and Jozefczyk, P. B. (1999) Therapeutics in the management of spasticity. Neurorehabil. Neural Repair 13, 5–14.CrossRefGoogle Scholar
  2. 2.
    Young, R. R. (1987) Physiologic and phamacological approaches to spasticity. Neurolog. Clin. 5, 529–39.Google Scholar
  3. 3.
    Young, R. R. (1994) Spasticity: a review. Neurology 44 (Suppl. 9), S12 - S20.PubMedGoogle Scholar
  4. 4.
    Young, R. R. (1995) Spastic paresis, in Diagnosis and Management of Disorders of the Spinal Cord ( Young, R. R. and Woolsey, R. M., eds.), Saunders, Philadelphia, pp. 363–376.Google Scholar
  5. 5.
    Little, J. W. and Massagli, T. L. (1993) Spasticity and associated abnormalities of muscle tone, in Rehabilitation Medicine: Principles and Practice, 2nd ed. ( DeLisa, J. A., ed.), Lippincott, Philadelphia, pp. 666–680.Google Scholar
  6. 6.
    Gelber, D. A. and Jozefczyk, P. B. (1999) Management of spasticity in multiple sclerosis. Intl. J. MS Care 1, 16–21.Google Scholar
  7. 7.
    Nance, P. W. (1997) Tizanidine an alpha2 agonist imidazoline with antispasticity effects. Today’s Therapeut. Trends 15, 11–25.Google Scholar
  8. 8.
    Coward, D. M. (1989) Pharmacology and mechanisms of action of tizanidine (Sirdalud), in Spasticity: The Current Status of Research and Treatment. ( Emre, M. and Benecke, R., eds.), Parthenon, Carnforth, UK, pp. 131–140.Google Scholar
  9. 9.
    Davies, J. and Johnston, S. E. (1983) Inhibition by DS 103–282 of D-(3-H)aspartate release from spinal cord slices. Br. J. Pharmacol. 78, 2 P.CrossRefGoogle Scholar
  10. 10.
    Curtis, D. R., Leah, J. D., and Peet, M. J. (1983) Spinal interneuron depression by DS-103–282. Br. J. Pharmacol. 79, 9–11.CrossRefPubMedGoogle Scholar
  11. 11.
    Wagstaff, A. J. and Bryson, H. M. (1997) Tizanidine: a review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs 53, 435–452.CrossRefPubMedGoogle Scholar
  12. 12.
    Davies, J., Johnston, S. E., Hill, D. R., and Quinlan, J. E. (1984) Tizanidine (DS 103–282), a centrally acting muscle relaxant, selectively depresses excitation of feline dorsal horn neurons to noxious peripheral stimuli by an action at alpha2-adrenoreceptors. Neurosci. Lett. 48, 197–202.CrossRefPubMedGoogle Scholar
  13. 13.
    Foote, S. L., Bloom, F. E., and Aston-Jones, G. (1983) Nucleus locus coeruleus: a new evidence of anatomical and physiological specificity. Physiol. Rev. 63, 844–914.PubMedGoogle Scholar
  14. 14.
    Strahlendorf, J. C., Strahlendorf, H. K., and Kinglsey, R. E., et al. (1980) Facilitation of the lumbar monosynaptic reflexes by locus coeruleus stimulation. Neuropharmacology 19, 225–230.CrossRefPubMedGoogle Scholar
  15. 15.
    Chen, D. F., Bianchetti, M., and Wiesendanger, M. (1987) The adrenergic agonist tizanidine has differential effects on flexor reflexes of intact and spinalized rats. Neuroscience 23, 641–647.CrossRefPubMedGoogle Scholar
  16. 16.
    Maramatsu, I. and Kigoshi, S. (1992) Tizanidine may discriminate between imidazoline-receptors and alpha-2 adrenoreceptors. Jpn. J. Pharmacol. 59, 457–459.CrossRefGoogle Scholar
  17. 17.
    Li, G., Regunathan, S., and Barrow, C. J., et al. (1994) Agmatine: an endogenous clonidine-displacing substance in the brain. Science 263, 966–969.CrossRefPubMedGoogle Scholar
  18. 18.
    Davies, J. (1982) Selective depression of synaptic transmission of spinal neurones in the cat by a new, centrally acting muscle relaxant, 5-chloro-4-(2imidazolin-2yl-amino)-2,1,3-benzothiadiazole (DS-103–282). Br. J. Pharmacol. 76, 473–481.CrossRefPubMedGoogle Scholar
  19. 19.
    Hassan, N. and McLellan, D. L. (1980) Double-blind comparison of single doses of DS 103–282, baclofen, and placebo for suppression of spasticity. J. Neurol. Neurosurg. Psychiatry 43, 1132–1136.CrossRefPubMedGoogle Scholar
  20. 20.
    Mathias, C. J., Luckitt, J., Desai, P., Baker, H., El Masri, W., and Frankel, H. L. (1989) Pharmacodynamics and pharmacokinetics of the oral antispastic agent tizanidine in patients with spinal cord injury. J. Rehabil. Res. Dey. 26, 9–16.Google Scholar
  21. 21.
    Emre, M., Leslie, G. C., Muir, C., Part, N. J., Pokorny, R., and Roberts, R. C. (1994) Correlations between dose, plasma concentrations, and antispastic action of tizanidine (Siralud®). J. Neurol. Neurosurg. Psychiatry 57, 1355–1359.CrossRefPubMedGoogle Scholar
  22. 22.
    Nance, P. W., Sheremata, W. A., Lynch, S. G., Vollmer, T., Hudson, S., Francis, G. S., and O’Conner, P., et al. (1997) Relationship of the antispasticity effect of tizanidine to the plasma concentration in patients with multiple sclerosis. Arch. Neuro1. 54, 731–736.CrossRefGoogle Scholar
  23. 23.
    Heazlewood, V., Symoniw, P., Maruff, P., and Eadie, M. J. (1983) Tizanidineinitial pharmacokinetic studies in patients with spasticity. Eur. J. Clin. Pharmacol. 25, 65–67.CrossRefPubMedGoogle Scholar
  24. 24.
    Hutchinson, D. R. (1989) Modified release tizanidine• a review. J. Intl. Med. Res. 17, 565–573.Google Scholar
  25. 25.
    Smith, C., Birnbaum, G., Carter, J. L., Greenstein, J., Lublin, F. D., and the US Tizanidine Study Group. (1994) Tizanidine treatment of spasticity caused by multiple sclerosis: results of a double-blind, placebo controlled trial. Neurology 44 (Suppl.9), S34 - S43.Google Scholar
  26. 26.
    Nance, P. W., Bugaresti, J., Shellenberger, K., Sheremata, W., Martinez-Arizala, A., and the North American Tizanidine Study Group. (1994) Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury. Neurology 44 (Suppl. 9), 544 - S52.Google Scholar
  27. 27.
    The United Kingdom Tizanidine Trial Group. (1994) A double-blind, placebo-controlled trial of tizanidine in the treatment of spasticity caused by multiple sclerosis. Neurology 44 (Suppl. 9), S70 - S78.Google Scholar
  28. 28.
    Ashworth, B. (1964) Preliminary trial of carisoprodel in multiple sclerosis. Practitioner 192, 540–542.PubMedGoogle Scholar
  29. 29.
    Medical Research Council. (1976) Aids to the Examination of the Peripheral Nervous System: Her Majesty’s Stationary Office, London, 1976.Google Scholar
  30. 30.
    Wallace, J. D. (1994) Summary of combined clinical analysis of controlled clinical trials with tizanidine. Neurology 44 (Suppl 9), S60–S69.Google Scholar
  31. 31.
    Gelber, D. A., Dromerick, A., Richardson, M., and Good, D. An open-label dose titration safety and efficacy study of Zanaflex (Tizanidine HC1) in the treatment of spasticity associated with chronic stroke. Stroke. In press.Google Scholar
  32. 32.
    Mahoney, E. I. and Barthel, D. W. (1965) Functional evaluation: The Barthel Index. MD Med. J. 14, 61–65.Google Scholar
  33. 33.
    Eysette, M., Rohmer, F., and Serratrice, G., et al. (1988) Multicentre double-blind trial of a novel antispastic, tizanidine, in spasticity associated with multiple sclerosis. Curr. Med. Res. Opin. 10, 699–708.CrossRefGoogle Scholar
  34. 34.
    Chrzanowski, C. (1980) A new muscle relaxant, DS 103–282, vs baclofen in the treatment of chronic spasticity (abstract), in Proceedings of the 8th International Congress of Physical Medicine and Rehabilitation, vol. 45, (Pedersen, E., ed.), Print MINAB, Stockholm.Google Scholar
  35. 35.
    Newman, R. M., Nogues, M., and Newman, R K., et al. (1982) Tizanidine in the treatment of spasticity. Eur. J. Clin. Pharmacol. 23, 31–35.CrossRefPubMedGoogle Scholar
  36. 36.
    Rinne, U. K. (1980) Tizanidine treatment of spasticity in multiple sclerosis and chronic myelopathy. Curr. Ther. Res. 28, 827–836.Google Scholar
  37. 37.
    Smolenski, C., Muff, S., and Smolenski-Kautz, S. (1981) A double-blind comparative trial of a new muscle relaxant, tizanidine, and baclofen in the treatment of chronic spasticity in multiple sclerosis. Curr. Med. Res. Opin. 7, 374–383.PubMedGoogle Scholar
  38. 38.
    Stien, R., Nordal, H. J., and Oftedal, S. I., et al. (1987) The treatment of spasticity in multiple sclerosis: a double-blind clinical trial of a new antispastic drug tizanidine compared with baclofen. Acta. Neurol. Scand. 75, 190–194.CrossRefPubMedGoogle Scholar
  39. 39.
    Van 0uwenaller, C. and Chantraine, A. (1985) A new myorelaxant in neurological affectations. J. Neurol. 235 (Suppl.), 305.Google Scholar
  40. 40.
    Hoogstraten, M. C., van der Ploeg, R. J., Vreeling, A., van Marie, S., and Minderhoud, J. M. (1988) Tizanidine vs baclofen in the treatment of spasticity in multiple sclerosis patients. Acta. Neurol. Scand. 77, 224–230.CrossRefPubMedGoogle Scholar
  41. 41.
    Jellinger, K. (1984) Zur Behandlung der Spastizitat bei multipler Sklerose-Ergebnisse einer Doppelblindstudie mit Tizanidin und Diazepham, in Die klinische Wertung der Spastizitat. ( Conrad, B., Benecke, R., and Bauer, H. J., eds.), Schattauer, Stuttgart, pp. 171–185.Google Scholar
  42. 42.
    Bes, A., Eyssette, M., and Pierrot-Deseilligny, E., et al. (1988) A multicentre double-blind trial of a new antispastic agent tizanidine, in spasticity associated with hemiplegia. Curr. Med. Res. Opin. 10, 709–718.CrossRefPubMedGoogle Scholar
  43. 43.
    Bass, B., Weinshenhenker, B., Rice, G. P., Noseworthy, J. H., Cameron, M. G., Hader, W., Bouchard, S., and Ebers, G. C.. (1988) Tizanidine vs baclofen in the treatment of spasticity in patients with multiple sclerosis. Can. J. Neurol. Sci. 15, 15–19.PubMedGoogle Scholar
  44. 44.
    Lataste, X., Emre, M., Davis, C., and Groves, L. (1994) Comparative profile of tizanidine in the management of spasticity. Neurology 44 (Suppl. 9), S53–S59.Google Scholar
  45. 45.
    Mizue, H. (1985) Clinical experience with tizanidine on infantile spastic paralysis. Jpn. J. Pediatr. 39, 701–708.Google Scholar
  46. 46.
    Imamura, S., Sakuma, K., Hirano, S., and Satou, N. (1985) Tizanidine treatment of hypertonus in cerebral palsied children. Jpn. J. Clin. Pediatr. 33, 325–331.Google Scholar
  47. 47.
    Kastrup, E. K. (ed.) (1999) Drug Facts and Comparisons. Wolters Kluwer Co, St. Louis.Google Scholar
  48. 48.
    Miettinen, T. J., Kanto, J. H., Salonen, M. A., and Scheinin, M. (1996) The sedative and sympatholytic effects of oral tizanidine in healthy volunteers. Anesth. Analg. 82, 817–820.PubMedGoogle Scholar
  49. 49.
    Luciani, A., Brugioni, L., Serra, L., and Grazilna, A. (1995) Sino-atrial and atrio-ventricular node dysfunction in a case of tizanidine overdose. Vet. Human. Toxicol. 37, 556–557.Google Scholar
  50. 50.
    de Graaf, E. M., Oosterveld, M., Tjabbes, T., and Stricker, B. H. (1996) A case of tizanidine-induced hepatic injury. J. Hepatol. 25, 772–773.CrossRefPubMedGoogle Scholar
  51. 51.
    Gelber, D. A. (1997) Neurogenic bowel and bladder, in Neurorehabilitation ( Lazar, R. B., ed.), McGraw-Hill Inc., New York, pp. 289–307.Google Scholar
  52. 52.
    Leyon, J. F., Martin, B. F., and Sporer, A. (1980) Baclofen in the treatment of detrusor-sphincter dyssynergia in spinal cord injury patients. J. Urol. 124, 82–84.Google Scholar
  53. 53.
    Hackler, R. H., Broecker, B. H., Klein, F. A., and Brady, S. M. (1980) A clinical experience with dantrolene sodium for external urinary sphincter hyper-tonicity in spinal cord injured patients. J. Urol. 124, 78–81.PubMedGoogle Scholar
  54. 54.
    Dykstra, D. D., Sidi, A. A., Scott, A. B., Pagel, J. M., and Goldish, G. D. (1988) Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J. Urol. 139, 919–922.PubMedGoogle Scholar
  55. 55.
    Berry, H. and Hutchinson, D. R. (1988) Tizanidine and ibuprofen in acute low-back pain: results of a double-blind multicentre study in general practice. J. Intl. Med. Res. 16, 83–91.Google Scholar
  56. 56.
    Mojica, J. A., Mancao, B. D., Perez, L. P., Zamuco, M. A., and Lorenzana, G. (1994) A dose-finding therapeutic trial on tizanidine in Filipinos with acute muscle spasm. Phil. J. Int. Med. 12, 141–145.Google Scholar
  57. 57.
    Lepisto, P. (1981) A comparative trial of tizanidine and placebo in patients with skeletal-muscle spasms after operation for herniated disc. Curr. Therapeut. Res. 30, 141–146.Google Scholar
  58. 58.
    Fryda-Kaurimsky, Z. and Muller-Fassbender, H. (1981) Tizanidine (DS 103282) in the treatment of acute paravertebral muscle spasm: a controlled trial comparing tizanidine and diazepam. J. Intl. Med. Res. 9, 501–505.Google Scholar
  59. 59.
    Goei Thé, H. S. and Whitehouse, I. J. (1981) A comparative trial of tizanidine and diazepam in the treatment of acute cervical muscle spasm. Clin. Trials J. 19, 20–28.Google Scholar
  60. 60.
    Hennies, O. L. (1981) A new skeletal muscle relaxant (DS 103–282) compared to diazepam in the treatment of muscle spasm of local origin. J. Intl. Med. Res. 9, 62–68.Google Scholar
  61. 61.
    Roosen, H. (1981) A comparative study of a new skeletal muscle relaxant tizanidine (DS 103–282) and chlormezanone. Clin. Trials J. 18, 321–332.Google Scholar
  62. 62.
    Fogelholm, R. and Murros, K. (1992) Tizanidine in chronic tension-type headache: a placebo controlled double-blind cross-over study. Headache 32, 509–513.CrossRefPubMedGoogle Scholar
  63. 63.
    Sakuta, M. and Takeda, K. (1991) Beneficial effect of tizanidine on the ischemic muscle contraction in chronic muscle contraction headache. Cephalalgia 11 (Suppl. 11), 339–340.Google Scholar
  64. 64.
    Shimomura, T., Awaki, E., and Kowa, H., et al. (1991) Treatment of tension-type headache with tizanidine hydrochloride: its efficacy and relationship to the plasma MHPG concentration. Headache 31, 601–604.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media New York 2002

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  • David A. Gelber

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