Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis.
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.
Nance
P W
PW
Section of Physical Medicine and Rehabilitation, University of Manitoba, Winnipeg, Canada.
Sheremata
W A
WA
Lynch
S G
SG
Vollmer
T
T
Hudson
S
S
Francis
G S
GS
O'Connor
P
P
Cohen
J A
JA
Schapiro
R T
RT
Whitham
R
R
Mass
M K
MK
Lindsey
J W
JW
Shellenberger
K
K
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
D000316:Adrenergic alpha-Agonists; D009125:Muscle Relaxants, Central; C023754:tizanidine; D003000:Clonidine