Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tizanidine, an imidazoline that acts as an agonist at alpha 2-adrenergic receptors, has been shown to be effective in reducing spasticity caused by MS. This multicenter study (14 sites) assessed the efficacy and safety of oral tizanidine in patients who had spinal cord injury of > 12 months' duration. Of the 124 patients admitted to the study, 78 completed it. Tizanidine was titrated to an optimized dosage in each patient to a maximum of 36 mg/d. Muscle tone, assessed by Ashworth score, was significantly reduced (p = 0.0001) by tizanidine treatment in comparison with placebo. Video motion analysis of the pendulum test showed improvement in the tizanidine-treated patients vs placebo (p = 0.04) and showed a significant correlation with the Ashworth score (p < 0.001). No significant alterations in muscle strength or vital signs were noted in either treatment group. The most common adverse events during tizanidine treatment were somnolence, xerostomia, and fatigue. It was concluded that, overall, tizanidine is effective in reducing spasticity in patients with spinal cord injury.
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PMID:Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury. North American Tizanidine Study Group. 797 10

The therapeutic profile of a new antispastic drug cannot be defined solely on the basis of placebo-controlled studies. Its potential advantages must be evaluated in comparison with existing drugs. This review compares the efficacy and tolerability of tizanidine, a newer muscle relaxant, with that of baclofen and diazepam, the most widely used antispastic agents, for a variety of diagnoses and target symptoms associated with spasticity. More than 20 double-blind, comparative studies were conducted between 1977 and 1987. These included a total of 777 patients suffering from spasticity of various causes. The collected clinical data have been integrated into a combined analysis. Tizanidine emerges from this comparison as a valuable drug in the treatment of spasticity related to cerebral and spinal disorders.
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PMID:Comparative profile of tizanidine in the management of spasticity. 797 11

Tizanidine was evaluated in a prospective, double-blind, randomized, placebo-controlled trial in 187 patients with MS. Taken orally for 9 weeks and preceded by a titration phase for a period of 3 weeks starting at 2 mg daily, tizanidine produced a significant reduction in spastic muscle tone compared with placebo treatment. Within the effective dose range of 24 to 36 mg given daily in three doses, tizanidine achieved a 20% mean reduction in muscle tone. Approximately 75% of patients, with all degrees of spasticity, reported subjective improvement without an increase in muscle weakness, but there was no improvement in activities of daily living depending on movement. Tizanidine achieved its maximum effect on spasticity within 1 week of the start of treatment; the benefit was maintained for at least 1 week after discontinuation of therapy. A variety of adverse events was recorded by patients taking tizanidine, but these were minor and reversible, and rarely limited treatment. Tizanidine is a well-tolerated and effective drug for symptomatic treatment of spasticity.
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PMID:A double-blind, placebo-controlled trial of tizanidine in the treatment of spasticity caused by multiple sclerosis. United Kingdom Tizanidine Trial Group. 797 14

This investigation estimated the mechanisms of tizanidine action on spasticity using a battery of neurophysiological methods. Thirty patients with old post-stroke spastic hemiparesis took part in the investigation. They were treated with tizanidine-mean daily dose 15.8 +/- 5.6 mg for a mean of 23.3 +/- 4.8 days. A questionnaire for assessment of subjective improvement after treatment used a 5-point scale. For standardization of the neurological examination 5-point scales were used to assess muscle tone, muscle force and tendon reflexes. A battery of neurophysiological methods was used to analyze different mechanisms of spasticity: for alpha motoneuron excitability--the F wave parameters; for presynaptic inhibition--the ratio of H reflex amplitudes before and after vibration of the achilles tendon (Hvibr/Hmax); for common interneuron activity--the flexor reflex parameters. Our results revealed that tizanidine reduces spastically increased muscle tone, but has no influence on muscle force, tendon reflexes, Babinski sign and ankle clonus. Tizanidine is supposed to act by increasing the presynaptic inhibition and decreasing of alpha motoneuron excitability. When spasticity has decreased presynaptic inhibition and increased motoneuron excitability, it is better to treat with tizanidine.
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PMID:Mechanisms of tizanidine action on spasticity. 804 46

Tizanidine, an imidazoline derivative with alpha 2-receptor-mediated central muscle relaxant activity, is in widespread clinical use for the treatment of spasticity. To evaluate its possible role in anesthesia we assessed the sedative and sympatholytic effects of orally administered tizanidine in a double-blind, placebo-controlled, randomized, cross-over study in six healthy male volunteers. Three different doses of tizanidine (4, 8, and 12 mg) were tested and compared to clonidine 150 micrograms. The sedative and sympatholytic effects of tizanidine 12 mg were comparable in magnitude to those of clonidine 150 micrograms, but the effects of clonidine were longer lasting. Similarly, the observed decreases in arterial blood pressure (diastolic, 13% and 19%; systolic, 10% and 8% for tizanidine and clonidine, respectively) and salivation were comparable in magnitude but of shorter duration after tizanidine 12 mg than after clonidine. Clonidine and tizanidine 12 mg had also similar effects on the secretion of growth hormone. Our results indicate that the effects of a single 12-mg oral dose of tizanidine resemble those of 150 micrograms oral clonidine, but are of shorter duration. Tizanidine may thus be a useful alternative to clonidine as an orally active, short-acting alpha 2-adrenoceptor agonist in the perioperative period.
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PMID:The sedative and sympatholytic effects of oral tizanidine in healthy volunteers. 861 3

The alpha 2-adrenergic agonist tizanidine was reported to be more efficient than baclofen in reducing muscle tone in some spastic patients. The aim of this study was to investigate if this might be due to more specific depressive actions of tizanidine on transmission from muscle afferents which contribute to muscle tone. This was done by comparing the effects of tizanidine and baclofen on amplitudes of monosynaptic spinal focal field potentials produced by stimulation of muscle nerves in the cat. Such field potentials were recorded in the intermediate zone of the fourth lumbar segment, where they display two distinct components, an early one from group I afferents and a later one from group II afferents. Both reflect EPSPs produced in interneurones in disynaptic pathways to motoneurones. Tizanidine strongly depressed potentials caused by group II afferents, while it had no effect or slightly facilitated potentials produced by group I afferents. In contrast, baclofen had inconsistent effects on the group II potentials; in some cases it caused a depression and in others it caused only an increase in the latency and time to peak, at doses that strongly and consistently depressed the group I potentials. These effects have been found after both local and systemic applications. The antispastic actions of tizanidine may therefore only be related to the depression of transmission from group II muscle afferents, while antispastic actions of baclofen may be secondary to the depression of any sensory fibres. Since tizanidine is as effective in depressing spasticity as baclofen, it is suggested that the enhancement in synaptic transmission from group II muscle afferents may play an important role in the development of exaggerated stretch reflexes in spastic patients.
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PMID:A comparison of the effects of two antispastic drugs, tizanidine and baclofen, on synaptic transmission from muscle spindle afferents to spinal interneurones in cats. 886 90

The central alpha 2 adrenoceptor agonist tizanidine is a myotonolytic agent used in the treatment of spasticity in patients with cerebral or spinal injury. Wide interpatient variability in the effective plasma concentrations of tizanidine means that the optimal dosage must be titrated over 2 to 4 weeks for each patient (dosages of 2 to 36 mg/day have been used in clinical trials). Maximum effects occur within 2 hours of administration. Antispastic efficacy has been demonstrated for tizanidine in placebo-controlled trials, with reduction in mean muscle tone scores of 21 to 37% versus 4 to 9% for patients receiving placebo. Improvement in muscle tone occurred in 60 to 82% of tizanidine recipients, compared with 60 to 65% of baclofen and 60 to 83% of diazepam recipients. Spasm frequency and clonus are also reduced by tizanidine. The most common adverse effects associated with tizanidine are dry mouth and somnolence/drowsiness. Muscle strength, as assessed by objective means, appears not to be adversely affected by tizanidine and subjective muscle weakness is reported less often by tizanidine recipients than by those receiving baclofen or diazepam. Global tolerability was assessed as good to excellent in 44 to 100% of patients receiving tizanidine, compared with 38 to 90% of baclofen and 20 to 54% of diazepam recipients. In conclusion, tizanidine is an antispastic agent with similar efficacy to that of baclofen and a more favourable tolerability profile. While drowsiness is a frequently reported adverse effect with both agents, subjective muscle weakness appears to be less of a problem with tizanidine than with baclofen. Tizanidine, therefore, appears to be an attractive therapeutic alternative for patients with spasticity associated with cerebral or spinal damage.
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PMID:Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. 907 44

Spasticity and other muscle symptoms in the palliative care patient can contribute to suffering, significantly detracting from overall quality of life. Current therapy primarily includes use of centrally acting muscle relaxants, which are beneficial in treating some symptoms, but frequently have extensive side effects, such as sedation and muscle weakness. Tizanidine, a central alpha 2 adrenergic agonist, has been shown in clinical studies to be as effective as other commonly used antispastic agents, but without debilitating muscle weakness. Tizanidine can cause sedation, which is minimized by dose titration. When taken at night, patients report improvement in getting to sleep and little drowsiness or "hangover sensation" upon waking. Tizanidine is potentially helpful to many palliative care patients with chronic muscle pain and sleep disturbances.
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PMID:Tizanidine in the management of spasticity and musculoskeletal complaints in the palliative care population. 1109 20

When spasticity produces a clinical disability by interfering with posture, motor capacity, nursing or daily living activities, medical treatment is recommended. It is mainly indicated when the muscle overactivity is diffusely distributed and should be implemented early, to prevent permanent musculoskeletal deformities or contractures. A pharmacological approach relies on the use of drugs which modulate neurotransmitters acting at the cortico-spinal level (GABA, glycine, glutamate, noradrenaline, serotonin). The aim of this treatment is to decrease spinal reflex excitability by reducing the release of excitatory neurotransmitters, or by potentiating the activity of inhibitory inputs. Evaluation of the efficacy of these drugs is determined by the therapeutic objectives which may be biomechanical, or functional. Diazepam increases presynaptic inhibition by stimulating GABA(A) receptors in the brainstem and spinal cord. In double-blind studies of patients with spinal cord lesions, antispastic efficacy has been shown, but side-effects are common. Baclofen stimulates GABA(B) receptors inducing a suppression of excitatory neurotransmitter release. Antispastic efficacy is sufficiently documented, but no definite effects on ambulation or activities of daily living have been proved. Tizanidine has an alpha2-agonist activity (at spinal and supraspinal level) and decreases the presynaptic activity of excitatory interneurones. The main clinical effects are a reduction in tonic stretch, polysynaptic reflexes, and co-contraction, with fewer side-effects but no definite functional change. The efficacy of several other antispastic drugs is documented in a few controlled studies, but the majority of information arises from open trials or anecdotal observations.
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PMID:The medical management of spasticity. 1191 47

Spasticity is one of the clinical signs observed after a lesion of the pyramidal tract. Clinical manifestations are polymorphous and depend on the location of the lesion on the pre-motoneuron. Functional consequences are also variable. Only negative effects such as painful spasms, stiffness, distortions, are to be treated. Three different categories of drugs are available: GABA-like (baclofen, benzodiazepine), central alpha 2 agonists (tizanidine, clonidine) and peripheral anti-spastics (dantrolene). Baclofen remains the most commonly used anti-spastic. The preferential indication is spasticity from spinal cord disease, especially when the aetiology is multiple sclerosis. Efficacy of benzodiazepines (diazepam, tetrazepam, clonazepam) is comparable with baclofen; however, side effects (drowsiness) are more frequent. Benzodiazepines are indicated when spasticity is associated with anxiety. Tizanidine is an efficient and well tolerated antispastic. In France, prescription requires a temporary authorization of use. Dantrolen has a peripheral mechanism of action and can be prescribed in the different forms of spasticity. There are other compounds with anti-spastic properties (gabapentine, cyproheptadine, piracetam). Their advantage is rather limited when used alone. Generally, they are administrated in combinaison with usual anti-spastic drugs.
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PMID:[Medical treatment of spasticity]. 1274 99


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