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)

Epileptiform activity was induced in area CA3 of hippocampal slices by superfusion of medium containing 50 microM bicuculline and 3.5 mM K, 50 microM bicuculline and 5 mM K, 50 nM kainic acid and 3.5 mM K, or 7 mM K. Burst potentials were recorded at rates between 5 and 44/min, depending on the convulsant treatment. Baclofen reduced the frequency of burst firing in all slices tested in a dose-dependent manner, with little change in the morphology of individual bursts. Thus baclofen primarily affected the initiation of epileptiform discharges. IC50 values varied between 27 and 500 nM and were positively correlated with the rate of bursting. These experiments indicate that baclofen, at concentrations present in the CSF of patients treated for spasticity, has an anticonvulsant-like effect in the hippocampal formation and suggest that its mode of action is to reduce the excitability of pyramidal cells.
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PMID:Baclofen suppresses bursting activity induced in hippocampal slices by differing convulsant treatments. 301 16

The literature regarding the intrathecal use of morphine, baclofen, and midazolam to treat spasticity is reviewed. Nine patients with significant spasticity due to different etiologies were treated. Morphine and midazolam decreased spasticity but did not change the patient's functional status. Baclofen improved patient status, but was associated with significant CNS depression in two cases.
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PMID:Intrathecal application of drugs for muscle hypertonia. 304 64

In about one third of patients with violent spasticity due to spinal trauma, multiple sclerosis, and diffuse brain injury adequate control with oral antispastic medication cannot be achieved and successful rehabilitation is severely handicapped. In the past these patients were subjected to destructive chemical procedures or extensive surgery. The authors present the results of management of uncontrollable spasticity by means of continuous intrathecal administration of baclofen with a totally implantable gas driven pump system (Infusaid). 30 patients were treated between June 1985 and January. 1987. The main indication was incapacitating spasticity resistant to oral treatment with baclofen and caused by spinal cord injury or lesion (11 patients), multiple sclerosis (11 patients), infantile cerebral palsy (3 patients) and cerebral injury, hypoxia or ischaemia (5 patients). Clinical assessment included spasticity scores, integrated electromyography (Iemg) and motography. Effective control for spasticity with mean reduction of Iemg by 55%, decrease of Ashworth's score from 3 to 0 and improvement of life quality was obtained in all patients with daily dose of 10-800 micrograms of Baclofen. Voluntary resting motoricity was not impaired and there were no untoward central side effects. The excellent effect of intrathecal baclofen in comparison with oral therapy is explained by local, spinal GABAergic inhibitory action of the drug which is delivered directly into spinal subarachnoid space. Dose finding and dose adjustment is performed prior to pump implantation by intermittent injections into a subcutaneous port. The complications of the procedure were minor (catheter displacement, disconnection) and easily correctable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Implanted pump systems for treatment of spasticity. 321 66

The functional impairment due to spasticity must be carefully assessed before any treatment is considered. Therapeutic intervention is best individualized to a particular patient. Basic principles of treatment to ameliorate spastic hypertonia are: 1) avoid noxious stimuli and 2) provide frequent range of motion. Therapeutic exercise, cold or topical anesthesia may decrease reflex activity for short periods of time in order to facilitate minimal motor function. Casting and splinting techniques are extremely valuable to extend joint range diminished by hypertonicity. Baclofen, diazepam and dantrolene remain the three most commonly used pharmacologic agents in the treatment of spastic hypertonia. Baclofen is generally the drug of choice for spinal cord types of spasticity, while sodium dantrolene is the only agent which acts directly on muscle tissue. Phenytoin with chlorpromazine may be potentially useful if sedation does not limit their use. Tizanidine and ketazolam, not yet available in the United States, may be significant additions to the pharmacologic armamentarium. Intrathecal administration of antispastic medications allows high concentrations of drug near the site of action, which limits side effects. This form of treatment is the most exciting recent development in the treatment of spastic hypertonia. Peripheral electrical stimulation may have limited use in diminishing tone and facilitating paretic muscles. Dorsal column stimulation via electrodes within the spinal column was initially hailed as a therapeutic advance, but has subsequently been shown to be minimally effective. Phenol injections provide a valuable transition between short-term and long-term treatments and offer remediation of hypertonia in selected muscle groups. Tenotomies and tendon transfers offer significant benefit in carefully chosen patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of spasticity. 328 46

Baclofen, a derivative of g-aminobutyric acid (GABA) has been known for many years to be a useful drug in the treatment of spinal spasticity. However, when the spasticity is severe, the systemic administration has to be increased, often without therapeutic effects but frequently with central side-effects. Baclofen given intrathecally however, in microgram doses has been previously reported to be effective and safe. A personal experience is reported of 9 severely spastic patients residing in chronic care facilities who were treated from July 1984 to March 1986 with intrathecal baclofen. The spasticity was causing significant nursing care problems, and 6 patients were reduced to a completely bedridden state. Each patient initially received a percutaneous intrathecal drug injection of 0.2-0.7 mg of baclofen to test its efficacy. A subcutaneous intrathecal system for further injections was placed in 6 patients. In 3 patients a decreased level of consciousness was observed. In the 3 cases of multiple sclerosis, intrathecal baclofen resulted in significant reduction of spasticity for 24 to 48 hours after each injection. The spasticity was improved in only one of the 2 cases of posttraumatic paraplegia. The effect was not convincing in the 2 cases of spinal cord tumour, and in the case of cerebral palsy the effect was improvement in spasticity, but also significant drowsiness. Baclofen, in comparison with some other drugs such as morphine or midazolam, also tried intrathecally by the authors, is the most effective in reducing spasticity. Its use however warrants caution, for it can cause decreased consciousness, and there is currently no antagonist.
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PMID:Intrathecal application of baclofen in the treatment of spasticity. 347 75

Baclofen at 20-40 mg/day was used to successfully treat two post-amputation patients who developed continuous complex involuntary movements of the proximal extremity. These autonomous movements were otherwise recalcitrant to therapy and were felt to arise from neural generators intrinsic to the spinal cord. Baclofen is known to be useful for spasticity of spinal etiology and now appears to be indicated for treatment of involuntary autonomous movements in post-amputation patients.
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PMID:Baclofen in the treatment of post-amputation autonomous stump movements. 356 67

Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino)-2,1,3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks. A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented. Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.
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PMID:Treatment of spasticity with tizanidine in multiple sclerosis. 367 23

Baclofen is an analog of the inhibitory neurotransmitter, GABA, which is used clinically to control spasticity. Recent evidence has accumulated showing this compound to have profound inhibitory effects upon hippocampal neural activity at both the cellular and circuit levels, and to attenuate epileptiform bursting in the hippocampal slice. However, it does not appear as an anticonvulsant on most traditional drug screens. Baclofen can produce inhibition by increasing potassium conductance, and therefore may fail to appear efficacious in typical anticonvulsant screens due to techniques that cause rapid and massive increases in interstitial potassium. We tested the hypothesis that baclofen is less effective at attenuating epileptiform bursting in the hippocampal slice under conditions of elevated extracellular potassium. Male Sprague-Dawley rats were decapitated and hippocampal slices were prepared. Epileptiform bursting was induced by bathing the slices in an artificial cerebrospinal fluid solution which contained either 7.0 mM K+ or 30 microM bicuculline methiodide, or by stimulus train-induced bursting. In each of these media, baclofen was applied in a random presentation of concentration format. Baclofen attenuated epileptiform bursting in both bicuculline and elevated K+, although considerably higher concentrations were necessary to attenuate bursting in high K+ than in bicuculline or after stimulus train-induced bursting. These results further support the antiepileptic actions of baclofen and provide evidence that this drug may be of value for attenuating epileptiform activity when there is not a tonic elevation of interstitial brain potassium.
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PMID:Attenuation of epileptiform bursting by baclofen: reduced potency in elevated potassium. 378 Sep 17

Seven patients with spasticity of spinal cord origin have been maintained for up to 2 years with continuous spinal intrathecal infusion of baclofen. Prior to treatment, all of the patients had severe rigidity in their lower limbs and most had frequent and extensive spontaneous spasms, all of which greatly interfered with their activities of daily living. Oral antispasmodic medications were ineffective or caused central side effects. The patients underwent implantation of a programmable drug pump connected to a lumbar subarachnoid catheter. Within days of beginning continuous intrathecal baclofen infusion, the muscle tone was reduced to normal levels and spasms were eliminated. Over the ensuing months, muscle tone remained normal, but short-duration spasms could be induced by some activities. The greatest benefits to the patients were improvement in activities of daily living and better sleep due to reduced spasms. The baclofen doses were increased over the first few months but then were stabilized or only increased slightly, with the maximum dose being 650 micrograms/day. The most serious complications were two drug overdoses which took several days to clear up and were due to malfunctions of an earlier pump model. Baclofen clearance from the cerebrospinal fluid occurs with a half-life of 5 hours. The most serious concern in maintaining patients indefinitely on intrathecal baclofen is whether drug tolerance will eventually occur.
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PMID:Long-term intrathecal baclofen infusion for treatment of spasticity. 380

Centrally acting muscle relaxant properties of AD-2239 were compared with those of tolperisone, eperisone, diazepam and baclofen. AD-2239 dose-relatedly depressed extensor reflex in urethane-chloralose anesthetized intact and spinal rats, the i.v. potencies being similar to those of tolperisone and eperisone. These effects of AD-2239 were long-lasting. When orally administered, AD-2239 was 4 times more potent than eperisone. Diazepam was without effect on the extensor reflex in spinal rats. AD-2239 depressed the flexor reflex without affecting the patellar reflex in anesthetized cats. Baclofen depressed the latter. When orally administered, AD-2239, in a dose-related manner, depressed the flexor reflex in anesthetized cats, with a potency approximately 8 times that of tolperisone or eperisone. AD-2239 produced a dose-related reduction of anemic decerebrate rigidity (alpha-rigidity) in rats. The potency, at the minimum effective i.v. dose, was 4 times greater than that of tolperisone or eperisone, equal to that of diazepam, and one-half of that of baclofen. AD-2239 neither affected spontaneous electroencephalogram (EEG) nor EEG arousal response in immobilized cats, while the other drugs, at comparatively low doses, depressed them. The results strongly suggest that AD-2239 may have advantages over the existing centrally acting muscle relaxants in the treatment of human clinical spasticity and muscle spasm syndromes.
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PMID:Pharmacological studies of 1-(2,3-dimethyl-4-methoxyphenyl)-2-methyl-3-(1-pyrrolidinyl)-1- propanone hydrochloride (AD-2239), a centrally acting muscle relaxant. 383 47


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