Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis

• Published in: Archives of neurology (Chicago) Vol. 54; no. 6; p. 731
• Main Authors: Nance, P W, Sheremata, W A, Lynch, S G, Vollmer, T, Hudson, S, Francis, G S, O'Connor, P, Cohen, J A, Schapiro, R T, Whitham, R, Mass, M K, Lindsey, J W, Shellenberger, K
• Format: Journal Article
• Language: English
• Published: United States 01-06-1997
• Subjects: Adrenergic alpha-Agonists - adverse effects; Adrenergic alpha-Agonists - blood; Adrenergic alpha-Agonists - pharmacology; Canada; Cardiovascular System - drug effects; Clonidine - adverse effects; Clonidine - analogs & derivatives; Clonidine - blood; Clonidine - pharmacology; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Multiple Sclerosis - blood; Multiple Sclerosis - drug therapy; Multiple Sclerosis - physiopathology; Muscle Contraction - drug effects; Muscle Relaxants, Central - adverse effects; Muscle Relaxants, Central - blood; Muscle Relaxants, Central - pharmacology; Severity of Illness Index; Treatment Outcome; United States; Canada; United States
• ISSN: 0003-9942
• DOI: 10.1001/archneur.1997.00550180049011

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.
To compare plasma concentrations of tizanidine with objective measures of muscle tone in patients with MS with moderate to severe spasticity.
Ten centers, all tertiary referral centers for the specialized treatment of patients with MS, in the United States and Canada.
A randomized, double-blind, placebo-controlled, dose-response study of tizanidine hydrochloride (8 or 16 mg).
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.
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.
Tizanidine reduces spasticity in MS, and both therapeutic effects and side effects are related to the plasma drug levels.