title: Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis.
abstract: BACKGROUND
  Spasticity is a serious problem in multiple sclerosis (MS) and many patients do not achieve a satisfactory response to currently available oral antispasticity drugs. Tizanidine hydrochloride, an alpha 2-noradrenergic agonist, has been shown to have an antispasticity effect in single center trials of patients with MS.
  
  
  OBJECTIVE
  To compare plasma concentrations of tizanidine with objective measures of muscle tone in patients with MS with moderate to severe spasticity.
  
  
  METHODS
  Ten centers, all tertiary referral centers for the specialized treatment of patients with MS, in the United States and Canada.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, dose-response study of tizanidine hydrochloride (8 or 16 mg).
  
  
  METHODS
  One hundred forty-two patients with spastic MS who were not taking any interfering medication, such as an antispasticity drug or other alpha-noradrenergic agonist, entered the trial.
  
  
  RESULTS
  Tizanidine treatment reduced muscle tone significantly, as shown by improved Ashworth scores and increased knee swing amplitude recorded by the pendulum test, both of which correlated significantly with plasma concentration. Placebo had no significant effect on muscle tone. Dizziness, drowsiness, dry mouth, and fatigue were reported most often in the group treated with tizanidine at peak plasma concentration.
  
  
  CONCLUSIONS
  Tizanidine reduces spasticity in MS, and both therapeutic effects and side effects are related to the plasma drug levels.
authors.affiliation: Section of Physical Medicine and Rehabilitation, University of Manitoba, Winnipeg, Canada.
authors.forename: P W
authors.initials: PW
authors.lastname: Nance
authors.forename: W A
authors.initials: WA
authors.lastname: Sheremata
authors.forename: S G
authors.initials: SG
authors.lastname: Lynch
authors.forename: T
authors.initials: T
authors.lastname: Vollmer
authors.forename: S
authors.initials: S
authors.lastname: Hudson
authors.forename: G S
authors.initials: GS
authors.lastname: Francis
authors.forename: P
authors.initials: P
authors.lastname: O'Connor
authors.forename: J A
authors.initials: JA
authors.lastname: Cohen
authors.forename: R T
authors.initials: RT
authors.lastname: Schapiro
authors.forename: R
authors.initials: R
authors.lastname: Whitham
authors.forename: M K
authors.initials: MK
authors.lastname: Mass
authors.forename: J W
authors.initials: JW
authors.lastname: Lindsey
authors.forename: K
authors.initials: K
authors.lastname: Shellenberger
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology*; D002170:Canada; D002319:Cardiovascular System / Q000187:drug effects; D003000:Clonidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D009125:Muscle Relaxants, Central / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
chemical_list: D000316:Adrenergic alpha-Agonists; D009125:Muscle Relaxants, Central; C023754:tizanidine; D003000:Clonidine