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)

Baclofendagger (Lioresal), a derivative of gamma-aminobutyric acid, was introduced in 1966 as a possible treatment for spasticity due to corticospinal tract lesions. Preliminary studies suggested that it may be more effective than other spasmolytic agents currently available, and a double-blind controlled trial in a group of 23 patients against placebo has shown it to be significantly more effective.
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PMID:Baclofen in the treatment of spasticity. 493 43

The high-affinity uptake of [3H]serotonin, [3H]glutamate, and [3H]gamma-aminobutyric acid [( 3H]GABA) and the Na+-independent binding of [3H]glutamate and [3H]GABA were studied using spinal cord preparations obtained from normal mongrel dogs and from dogs made paraplegic by midthoracic spinal cord crush. Lumbosacral regions of the spinal cord were removed either before (1 week) or after (3 to 8 weeks) onset of spasticity. A myelin-free synaptosomal fraction was obtained by centrifugation and used for studying high-affinity uptake and for preparing synaptic plasma membranes for Na+-independent binding experiments. For the paraplegic groups, the uptake of 30 nM [3H]serotonin was 66 and 18% of control values after 1 and 3 weeks, respectively. Eadie-Hofstee analysis of [3H]serotonin uptake showed a 90% reduction in Vmax for the paraplegic group relative to control values, thereby indicating the expected loss of descending serotonergic pathways. The high-affinity uptakes of 1 microM [3H]glutamate and [3H]GABA were the same in both the control and nonspastic paraplegic groups after 1 week. However, after 3 weeks, the uptakes of [3H]glutamate and [3H]GABA were 60-70% higher for the spastic group than for the control animals. For both amino acids, Eadie-Hofstee plots revealed no difference in Km and higher Vmax for the spastic group relative to control values. After 1 and 3 weeks, the Na+-independent binding of 5 nM [3H]glutamate was 40-85% higher and the binding of 10 nM [3H]GABA was 40-60% lower for the paraplegic groups relative to the values for the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations of amino acid transmitter systems in spinal cords of chronic paraplegic dogs. 614 26

Baclofen is a gamma-aminobutyric acid (GABA) agonist approved for the treatment of spasticity and commonly used in the management of many types of neuropathic pain. Controlled studies have demonstrated the efficacy of this drug in trigeminal neuralgia. Although its precise mechanism of analgesic action is unknown, it is likely that a drug-induced increase in inhibitory activity is sufficient to interrupt the cascade of neural events that culminates in aberrant activity of wide dynamic range neurons, or more rostral neurons in nociceptive pathways, that is the substrate for some types of neuropathic pain. The optimal use of baclofen as an adjuvant analgesic requires an understanding of its pharmacology, side effect spectrum, and dosing guidelines that have proven useful in clinical practice. Failure of baclofen therapy following a prolonged trial requires dose tapering prior to discontinuation due to the potential for a withdrawal syndrome.
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PMID:Baclofen as an adjuvant analgesic. 785 58

Baclofen, a centrally acting gamma-aminobutyric acid agonist is a commonly used pharmacotherapy for spasticity of spinal origin. It is primarily excreted by glomerular filtration with a clearance proportional to creatinine clearance. We describe a 39-year-old quadriplegic women who, over a 16-week period, developed clinical signs of baclofen toxicity confirmed by progressively rising serum baclofen levels while on a conventional stable dosing regimen. During this period blood urea nitrogen and creatinine concentrations were normal and stable (9mg/dL and 0.8mg/dL, respectively). However, creatinine clearance values were consistently low (55 to 60m/min), suggesting renal insufficiency as the underlying cause. After a decrease in baclofen dosage, evidence of baclofen toxicity resolved. Clinicians should be alert to signs of evolving baclofen toxicity even in patients on an apparently stable regimen. Baclofen dosage adjustments based on systemic baclofen level may play a role in optimizing the clinical management of spasticity.
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PMID:Baclofen toxicity in a patient with subclinical renal insufficiency. 829 51

Baclofen (Lioresal) is a derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). It is used to treat spasticity particularly for the relief of flexor spasms, pain, clonus, and muscular rigidity. There have been many rare neurologic side effects reported with its use. These side effects, in particular, hallucinations and seizures, have been observed predominantly following precipitous withdrawal of the drug. We present a case demonstrating a muscular dyskinetic side effect when baclofen treatment was first initiated. The mechanism by which baclofen affects spasticity and how the resulting side effect of dyskinesia developed in our patient is not known. They are, however, most probably related to dopamine receptor hypersensitivity and the resulting imbalance of the dopaminergic/cholinergic systems. Clinicians should be aware of this additional adverse effect of muscular dyskinesia, with the use of baclofen, and its reversibility when baclofen is discontinued.
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PMID:Baclofen-induced dyskinesia. 832 1

At present, it is not clear why drug tolerance develops in patients receiving intrathecal baclofen for the chronic treatment of spasticity of spinal origin. To investigate the mechanisms of tolerance to the gamma-aminobutyric acid (GABAB) agonist baclofen, rats were implanted with intrathecal catheters and continuously infused with either the drug or saline for 1, 3, or 7 days. The dose chosen, 1 microgram/hr, initially caused profound hindlimb motor weakness, but by Day 7 the rats had adapted to the drug and exhibited only minimal motor impairment. The animals were sacrificed on Day 1, 3, or 7 and quantitative autoradiography was used to determine the binding density and affinity of the GABAB receptors in the substantia gelatinosa of the lumbar spinal cord. After 1 day of drug infusion there was no change in binding parameters, but after 3 and especially after 7 days there was a significant decrease in the GABAB binding density (74% and 66%, respectively) in baclofen-treated rats as compared to saline-treated control rats. This GABAB receptor down-regulation correlated with tolerance to the motor weakness in the baclofen-treated animals and suggests that similar mechanisms contribute to drug tolerance in patients.
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PMID:Intrathecal baclofen down-regulates GABAB receptors in the rat substantia gelatinosa. 841 Feb 24

Baclofen, a gamma-aminobutyric acid agonist, acts at the spinal cord level to impede the release of excitatory neurotransmitters that cause spasticity. Oral baclofen improves cerebral spasticity mildly, but its activity is limited because of its poor lipid solubility. Cerebrospinal fluid baclofen levels after intrathecal administration are many times higher than those achieved after oral administration. Continuous intrathecal baclofen infusion has been used to treat cerebral spasticity in two patient groups: in older ambulatory children with inadequate underlying leg strength, and in patients with severe spasticity in both the upper and lower extremities. Responsiveness to intrathecal baclofen is confirmed by test injections before insertion of a programmable subcutaneous pump. Continuous intrathecal baclofen infusion dosages vary from 27 to 800 micrograms/day. Continuous intrathecal baclofen infusion reduces spasticity in the upper and lower extremities, and improves upper extremity function and activities of daily living but has no effect on athetosis in the dosages used to treat spasticity. Complications related to the intrathecal catheter occur in approximately 20% of patients, and infection requiring pump removal occurs in approximately 5%. Preliminary studies indicate that continuous intrathecal baclofen infusion alleviates some forms of generalized dystonia associated with cerebral palsy.
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PMID:Baclofen in the treatment of cerebral palsy. 888 81

GABAB (gamma-aminobutyric acid)-receptors have been implicated in central nervous system (CNS) functions, e.g. cognition and pain perception, and dysfunctions including spasticity and absence epilepsy. To permit an analysis of the two known GABAB-receptor splice variants GABAB-R1a (GB1a) and GABAB-R1b (GB1b), their distribution pattern has been differentiated in the rat brain, using Western blotting and immunohistochemistry with isoform-specific antisera. During postnatal maturation, the expression of the two splice variants was differentially regulated with GB1a being preponderant at birth. In adult brain, GB1b-immunoreactivity (-IR) was predominant, and the two isoforms largely accounted for the pattern of GABAB-receptor binding sites in the brain. Receptor heterogeneity was pronounced in the hippocampus, where both isoforms occurred in CA1, but only GB1b in CA3. Similarly, in the cerebellum, GB1b was exclusively found in Purkinje cells in a zebrin-like pattern. The staining was most pronounced in Purkinje cell dendrites and spines. Using electron microscopy, over 80% of the spine profiles in which a synaptic contact with a parallel fibre was visible contained GB1b-IR at extrasynaptic sites. This subcellular localization is unrelated to GABAergic inputs, indicating that the role of GABAB-receptors in vivo extends beyond synaptic GABAergic neurotransmission and may, in the cerebellum, involve taurine as a ligand.
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PMID:GABAB-receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization. 1010 70

Baclofen, an analog of the putative inhibitory neurotransmitter gamma-aminobutyric acid is capable of crossing the blood-brain barrier. The drug has been shown to have an antinociceptive action and is used effectively in the management of spasticity. Baclofen was first used in the treatment of trigeminal neuralgia in 1980 and is currently used in the management of various types of neuropathic pain. The effect of baclofen on migraine has not been previously studied. The aim of the present open pilot study was to evaluate the efficacy of baclofen in patients with migraine. Fifty-four patients with migraine with and without aura who experienced 4-8 migraine attacks during a 4-week baseline were included. Baclofen, 15-40 mgs, was given in three divided doses for 12 weeks. Headache frequency and severity were recorded. Fifty-one patients completed the trial. Baclofen was found to be effective in 86.2% with > or = 50% headache reduction from baseline. Three patients could not tolerate the drug due to adverse events. In this open study, baclofen was found to be effective for prophylactic treatment of migraine.
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PMID:Baclofen for prevention of migraine. 1044 46

Preliminary pharmacologic evidence suggests that tiagabine, a new presynaptic gamma-aminobutyric acid-uptake inhibitor developed as an antiepileptic drug, may also relieve spasticity. This pilot study assessed the drug's efficacy in 14 children with congenital or acquired spastic quadriplegia and concomitant intractable epilepsy refractory to treatment with multiple antiepileptic drugs. The primary outcome variable was change in motor function; the secondary outcome was change in seizure frequency. Tiagabine was initiated at 0.1-0.2 mg/kg/day and then gradually titrated upward until seizures ceased, adverse effects supervened, or the maximum dose of 1.1 mg/kg/day was reached. When a modified Ashworth scale was used to assess motor function, a mean improvement of approximately 50% was observed. Common findings included improved tone, strength, coordination, range of motion, and relaxation of extremities, with less ataxia and wobbling. Mean reduction in seizure frequency was 50-74%. Randomized, double-blind controlled studies are needed to confirm the suggested efficacy of tiagabine in relieving chronic spasticity in children with neurodevelopmental disorders.
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PMID:The effect of tiagabine on spasticity in children with intractable epilepsy: a pilot study. 1058 Aug 85


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