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For this updated review we searched the Cochrane Neuromuscular Disease Group Specialized Register (30 April 2010). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to April 2010), EMBASE (January 1980 to April 2010), LILACS (January 1982 to April 2010) and the Chinese Biomedical Retrieval System (1978 to April 2010). We handsearched 10 Chinese journals.
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Cerebral blood flow to the left hemisphere of adult Sprague-Dawley rats (n=48) was temporarily interrupted by middle cerebral artery and bilateral common carotid artery occlusion for 3 hours in eight rats of each group. Tizanidine was given to each group of rats intraperitoneally before the ischemic insult, 2 hours after ischemia, right after the reperfusion, 2 h after reperfusion, and 4 hours after reperfusion; the animals survived for 24 hours after the reperfusion. After killing and triphenyltetrasoliumchloride staining of brain slices, infarction volumes and ratios of the brains were calculated and the results were compared with those of the control group.
A randomized double-blind cross-over study was performed to compare the efficacy of Tizanidine to that of placebo in the treatment of spasmodic torticollis. No evidence was found that Tizanidine was effective in 10 patients with spasmodic torticollis who received Tizanidine during 6 weeks, up to a dose of 12 mg a day.
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Thirty-nine patients with more than 15 headache days per month (33 with migraine, 5 migrainous, 1 chronic tension-type) completed a 4-week baseline, with 31 completing a planned 12 weeks of treatment with tizanidine. Dosing was titrated from 2 mg at bedtime to a median daily dose of 14 mg (mean, 13.5; SD, 4.3; range, 4 to 20, divided over three doses per day) by treatment week 4.
We investigated the involvement of the spinal cord melanocortin (MC) system in neuropathic pain. Because we recently demonstrated that MC receptor ligands acutely alter nociception in an animal model of neuropathic pain, in this study we tested whether chronic administration was also effective. We hypothesized that chronic blockade of the spinal MC system might decrease sensory abnormalities associated with this condition. The effects of the MC receptor antagonist SHU9119 (0.5 microg/d) and agonist MTII (0.1 microg/d) were evaluated in rats with a chronic constriction injury of the sciatic nerve. Drugs were continuously infused into the cisterna magna. Antinociceptive effects were measured with tests involving temperature (10 degrees C or 47.5 degrees C) or mechanical (von Frey) stimulation. The administration of MTII increased mechanical allodynia, whereas SHU9119 produced a profound cold and mechanical antiallodynia, altering responses to control levels. The antiallodynic effects of SHU9119 were very similar to those produced by the alpha(2)-adrenergic agonist tizanidine (50 microg/d). The effects of SHU9119 and MTII are most likely mediated through the MC4 receptor, because this is the only MC-receptor subtype present in the spinal cord. We conclude that the chronic administration of MC4-receptor antagonists might provide a promising tool in the treatment of neuropathic pain.
Chronic daily headache (CDH), a heterogeneous group of headache disorders occurring on at least 15 days per month, affects up to 4% to 5% of the general population. CDH disorders include transformed (or chronic) migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Patients with CDH have greater disability and lower quality of life than episodic migraine patients and often overuse headache pain medications. To date, only topiramate, gabapentin, tizanidine, fluoxetine, amitriptyline, and botulinum toxin type A (BoNTA) have been evaluated as prophylactic treatment of CDH in randomized, double-blind, placebo-controlled, or active comparator-controlled trials. The evidence supporting the use of BoNTA as prophylaxis of CDH is composed of larger and longer trials, as over 1000 patients were evaluated for up to 11 months duration. Compared with placebo BoNTA has significantly reduced the frequency of headache episodes, a recommended efficacy measure for headache trials and has been demonstrated to be safe and very well tolerated with few discontinuations due to adverse events. Side effects are generally transient, mild to moderate, and nonsystemic. The results of clinical trials using traditional oral pharmacotherapy, while supportive of their use as prophylactic treatment of CDH, are limited by several factors, including small numbers of patients, the choice of efficacy measures, and short treatment periods. The use of oral agents was associated with systemic side effects, which may limit their effectiveness as prophylactic treatment of CDH.
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Based upon the literature review, the hypotension in this patient was possibly due to the interaction between tizanidine and lisinopril.
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(1) Whole-cell patch-clamp experiments: HERG- or KCNQ1+KCNE1-transfected cells were exposed to tizanidine 0.1-100 µmol/L (n = 29 cells, total) to assess drug effect on the rapid (I(Kr)) and slow (I(Ks)) components of the delayed rectifier potassium current. (2) Langendorff retroperfusion experiments: isolated hearts from male Hartley guinea pigs (n = 6) were exposed to tizanidine 1 µmol/L to assess drug-induced prolongation of monophasic action potential duration measured at 90% repolarization (MAPD(90)). (3) In vivo wireless cardiac telemetry experiments: guinea pigs (n = 6) implanted with radio transmitters were injected a single intraperitoneal (ip) dose of tizanidine 0.25 mg/kg and 24 hours electrocardiography (ECG) recordings were made.
Spasticity (muscle rigidity and spasms) is a frequent and disabling feature of multiple sclerosis (MS), and it can have a marked negative impact on the patient's overall wellbeing and quality of life through a range of symptoms including impaired mobility, bladder dysfunction, stiffness, spasms and sleep disorders. Numerous antispastic agents such as baclofen and tizanidine, as well as others, are available for the management of MS spasticity but, overall, they offer limited clinical benefit. The current questionnaire survey assessed the epidemiology and management of MS spasticity globally and across the EU, among 157 healthcare professionals (>95% of all respondents were neurologists) attending a large, international MS congress (European Committee for Treatment and Research in Multiple Sclerosis, Lyon, France, 10-13 October 2012). Survey results showed similarity between the EU and rest-of-world respondents in the epidemiology of MS spasticity, the use of assessment tools to monitor patients, the incidence and severity of symptoms, and management options. Respondents indicated that approximately 40% of their MS patients had spasticity and it was rated as mild in approximately 40%, moderate in 35% and severe in 25% of patients. At least 40% of practitioners were dissatisfied with treatment options in their patients with moderate-to-severe MS; this highlights the unmet needs and challenges facing specialists in the management of MS patients with moderate-to-severe spasticity.
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The aim of this study was to determine whether mexiletine, a CYP1A2 inhibitor, altered the pharmacokinetics and pharmacodynamics of tizanidine. The pharmacokinetics of tizanidine were examined in an open-label study in 12 healthy participants after a single dose of tizanidine (2 mg) with and without mexiletine coadministration (50 mg, 3 times as a pretreatment for a day and 2 times on the study day). Compared with tizanidine alone, mexiletine coadministration increased the peak plasma concentration (1.8 +/- 0.8 vs 5.3 +/- 1.8 ng/mL), area under the curve (4.5 +/- 2.2 vs 15.4 +/- 6.5 ng x h/mL), and the half-life (1.3 +/- 0.2 vs 1.8 +/- 0.7 h) of tizanidine, respectively (P < .05). Reduction in systolic blood pressure (-10 +/- 8 vs -24 +/- 7 mm Hg) and diastolic blood pressure (-10 +/- 7 vs -18 +/- 8 mm Hg) after tizanidine administration was also significantly enhanced by coadministration of mexiletine (P < .01). Of the 15 patients treated with tizanidine and mexiletine, 4 suffered tizanidine-induced adverse effects such as drowsiness and dry mouth in the retrospective survey. Present results suggested that coadministration of mexiletine increased blood tizanidine concentrations and enhanced tizanidine pharmacodynamics in terms of reduction in blood pressure and adverse symptoms.