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)

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.
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PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

Dantrolene sodium is a muscle relaxant used in the treatment of spasticity. It has been shown to interfere with calcium release from the sarcoplasmic reticulum and thus to inhibit excitation--contraction coupling. The effect of dantrolene sodium on the twitch tension of the tibialis anterior muscle of the rat was measured after 2 mg/kg i.v. or 25 mg/kg orally. Plasma concentrations were estimated at maximum twitch depression and during recovery from the block. In a separate series of experiments the half-life of labelled dantrolene sodium was measured in blood plasma, skeletal muscle and heart muscle of rats. Dantrolene sodium 2 mg/kg i.v. gave a maximal block of approximately 47%, the mean dantrolene sodium concentration was then 5.8 microgram/ml. A half-life for distribution of 1.1 min and an elimination half-life of 31 min after intravenous administration were observed, elimination rate constants in skeletal and heart muscle were comparable. Recovery from the block went much slower, the half-time of the process being approximately 80 min. Dantrolene sodium 25 mg/kg orally gave a maximal block of approximately 38% at a mean plasma concentration of 3.6 microgram/ml after 14 min. The recovery was again very slow. These experiments demonstrated that dantrolene sodium acts according to a two-compartment pharmacokinetic model. There was a discrepancy between duration of effect and plasma concentration of dantrolene sodium in the rat. This suggests that the receptor for dantrolene sodium is not located in the central compartment.
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PMID:The effect of dantrolene sodium on rat skeletal muscle in relation to the plasma concentration. 42 31

Dantrolene sodium has been given to 45 patients suffering from dyskinetic syndromes: 33 were suffering from spastic syndromes, either secondary to cerebral lesions at birth, or to other cerebral lesions, or to cord lesions; 9 were affected by infantile dystonic syndromes; 1 by dystonia muscolorum deformans and the last 2 patients were suffering from parkinsonism. The best dosage schedule was individual and ranged from 50 mg to 300 mg a day. In this range, the majority of the spastic patients showed reduction of spasticity, unrelated with the site of pathology: a slight one in 12 patients, a moderate one in 9 and a marked one in 2. On the contrary, slight improvement has been noticed in only two of the patients suffering from dystonic syndromes. In no case side effects has been noticed. In all patients who underwent slight or moderate improvement only, we tried to obtain better results on spasticity by growing the dosage schedules; but we have always noticed side effects, that is weakness or drowsiness and, sometimes, urinary uncontinence. Moreover 2 patients showed evidence of transitory metabolic side effects. Therefore our experience shows that dantrolene sodium is an useful drug into the therapy of spasticity, even if often a slight of moderate improvement only is achieved. Slow increase in dosage schedule, repeated laboratory controls and alternate periods of treatment and suspended treatment should be observed.
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PMID:[Clinical study of dantrolene sodium in the treatment of spastic and dystonic syndromes]. 102 44

Dantrolene sodium (Dantrium) is a skeletal muscle relaxant, unique in that it acts on the muscle itself. It should be considered for use in patients with skeletal muscle spasticity who are in a stable neurological state. After careful adjustment of the dose, a substantial number of such patients will experience one or more of the following benefits: (1) a reduction in pain, (2) an increased ability to make use of residual motor function, (3) a reduction in the level of nursing care required, (4) an increased ability to utilize devices, and (5) an increased ability to participate in rehabilitation. The drug should not be used when reduced spasticity will decrease functional ability. The adverse effects generally are transient; some are the result of central nervous system depression.
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PMID:Evaluation of a muscle relaxant: dantrolene sodium (Dantrium). 108 67

The effects of dantrolene sodium (Dantrium) were studied in 23 patients with hemiplegic spasticity, 13 of whom were younger than 50, and 10 older than 50. The dosage of dantrolene ranged from 100 mg per day initially to 600 mg per day maximally. The drug was most effective in reducing or abolishing clonus and somewhat less efficacious in decreasing the resistance to stretch and the tendon reflexes. Functionally, gait was improved and the patients found it easier to take care of their personal needs. In general, motor performance was improved. The observation that patients in the 50+ age group responded less well remains unexplained. Dantrolene sodium is a valuable tool in the management of spasticity due to hemiplegia.
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PMID:Effect of dantrolene sodium on spasticity associated with hemiplegia. 114 24

Dantrolene sodium is a drug used in the treatment of spasticity and malignant hyperthermia. It is known to have a myorelaxant effect related to inhibition of the "release" of calcium by the sarcoplasmic reticulum of striated skeletal muscle. A direct cardiac effect which has only recently been suspected was demonstrated in vitro on isolated preparations of sheep Purkinje fibres and ventricular myocardium. Dantrolene caused a spectacular lengthening of the duration of the action potential of Purkinje fibres. This could be due either to an action on the slow calcium current or to stimulation of an ingoing sodium current sensitive to tetrodotoxin (TTX). This effect on the cardiac action potentials could explain the antiarrhythmic properties of dantrolene sodium during attacks of malignant hyperthermia.
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PMID:[In vitro electrophysiological effects of sodium dantrolene on isolated preparations of Purkinje fibers and ventricular myocardium of sheep]. 242 77

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.
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PMID:Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. 352 59

Spasticity is an important cause of physical impediment in multiple sclerosis. Only drug therapy offers useful (but not universal) relief. Dantrolene sodium and/or baclofen are the drugs of choice, being both effective and clinically suitable in over half of cases when carefully titrated and monitored.
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PMID:Muscle relaxants in multiple sclerosis. 368 Jan 9

Dantrolene sodium was effective in controlling spasticity and improving function in 11 of 13 patients taking part in a 14-week double-blind crossover study. Clonus and lower-extremity tendon jerks were reduced in almost all patients (10 and 11 respectively) during dantrolene sodium therapy at 200 to 400 mg/day. Activities of daily living showed marked improvement in 3 cases and moderate improvement in 8. All 13 patients reported decreases in the frequency of intermittent painful spasm. Side effects were minimal and consisted mainly of an initial 3- to 4-day period of weakness and lightheadedness.
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PMID:Efficacy of dantrolene sodium in the treatment of spasticity. 1789 68

Though in the last few decades only a few new drugs have come available for the treatment of spasticity, new insights may revise the role and individual value of several pharmacological treatments. Diazepam, baclofen and tizanidine are the most prescribed drugs for the treatment of spasticity. Intrathecal baclofen and local infiltration of botulin toxin are added values in selective patients. Gabapentin is a novelty, and the working mechanism of cannabis has been elucidated. Dantrolene sodium appears to owe its selectivity from the recently discovered ryanodine receptor, with a peripheral effect in muscles. In this review the pathophysiology and epidemiology of spasticity, pharmacology, clinical efficacy and unwanted effects of the different drugs for spasticity are updated.
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PMID:Spasticity: revisiting the role and the individual value of several pharmacological treatments. 2087 Nov 49


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