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

Dyskinetic, writhing-like movements, similar to those produced in mice after an intraperitoneal (IP) injection of acetic acid, were elicited by intrathecal (IT) injection of GABA, glycine, taurine or beta-alanine. Baclofen and muscimol failed to produce this behavior. While acetic acid-induced writhing is inhibited by narcotic and nonnarcotic compounds, GABA-induced writhing was found to be insensitive to pretreatment with either morphine or capsaicin. Moreover, acetic acid-induced writhing does not appear to involve GABAergic transmission as IT injections of nipecotic acid did not alter the intensity of response to IP acetic acid while it enhanced the response to IT GABA. Writhing induced by glycine was not inhibited by strychnine at subconvulsive doses, suggesting that it involves an action at strychnine-insensitive receptors. Together these data suggest that while the dyskinetic movements produced by inhibitory amino acids do not appear to reflect an alteration in nociception, they may mimic either the motor response to abdominal pain or spasticity.
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PMID:Intrathecal GABA, glycine, taurine or beta-alanine elicits dyskinetic movements in mice. 272 12

Intrathecal administration of Baclofen, a GABA agonist, through an implantable drug delivery pump has been demonstrated to be effective in the treatment of limb spasticity in patients with myelopathy. Three patients, followed before and after pump placement, experienced satisfactory spasticity relief and improvement in areas of self-care and mobility. Improvement in the bladder management programs of each patient was noted. These changes coincided with improvement on urodynamic studies, defined as either an increase in bladder capacity or a decrease in sphincter dyssynergia. Changes in bladder function were associated with the initiation of intrathecal therapy and with changes in pump-delivered dosages. In selected patients, intrathecal baclofen infusion can have a beneficial effect on bladder management programs.
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PMID:Intrathecal baclofen infusion. Effect on bladder management programs in patients with myelopathy. 273 Jul 79

Familial spastic paraplegia (FSP) was recorded in three families. The pattern of familial transmission and the onset in the second and third decade of life strongly suggested autosomal dominant inheritance. FSP in this series showed the consistent, classical, clinical features with some inconstant findings (nystagmus, dysarthria, posterior column involvement). Baclofen for the treatment of spasticity is beneficial in this condition and genetic counselling should be considered.
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PMID:Familial spastic paraplegia. 273 87

Baclofen, a centrally acting muscle relaxant, is used in the treatment of spasticity. Its pharmacokinetics has been derived from plasma and urine data in four healthy subjects, whose renal function was simultaneously measured. After oral administration of a single 40 mg dose, baclofen was mainly excreted unchanged by the kidney, 69 (14)%. The half-life, calculated from extended least squares modelling (ELSMOS) both of plasma and urine data was 6.80 (0.68) h, which is longer than reported in most studies based solely on plasma data. The renal excretion rate constant had the high mean value of 0.35 (0.24) h-1, and the apparent renal clearance of baclofen equalled the creatinine clearance. Passive tubular reabsorption is relatively unimportant, since no dependence was observed on variables urine flow or pH. Although active tubular secretion may contribute to its renal clearance, as shown by the effect of co-administration of probenecid, glomerular filtration appears to be the dominant transport mechanism.
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PMID:Plasma and urinary excretion kinetics of oral baclofen in healthy subjects. 279 73

Baclofen was given intrathecally to six patients with severe lower limb spasticity due to traumatic spinal cord injury. The effects of the drug on spasticity and the ratio between the maximum amplitude of the H reflex and the M response from the soleus (Hmax/Mmax ratio) were assessed. In each patient, spasticity was reduced following intrathecal baclofen and in four patients there was a reduction in the amplitude of the H reflex and Hmax/Mmax ratio. These results suggest that the Hmax/Mmax ratio may be helpful in establishing optimum drug dosage, particularly when the drug is used on a chronic basis.
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PMID:Intrathecal baclofen and the H-reflex. 279 85

Baclofen (Lioresal, Ciba-Geigy) is an analog of the inhibitory neurotransmitter GABA and is used clinically to control spasticity. Recent studies have demonstrated that this compound produces a marked inhibition of synaptically evoked responses in area CA3 of the hippocampal slice, suggesting that this drug could influence behavior mediated by the limbic system. In the present study, male rats of the Fischer-344 strain were trained on a one-trial passive avoidance task and tested for retention 1 week later. After the training trial, separate groups of rats received either 5 or 10 mg/kg/4 ml IP of baclofen or the distilled H2O vehicle immediately, 10 min, or 60 min after training. One week later, the rats that received baclofen immediately after training reentered the test chamber with a significantly higher frequency than controls, although no differences in vacillatory responses were observed between groups. Similar effects were observed following posttrial administration of chlordiazepoxide. In a separate experiment rats were tested for locomotor activity after receiving the same doses of baclofen. Although baclofen decreased activity during a 30-min period after dosing, rats exposed to baclofen showed no significant change in activity relative to controls 1 week later. These data are consistent with the interpretation that baclofen may interfere with memory consolidation or retention.
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PMID:Baclofen disrupts passive avoidance retention in rats. 281 19

Several different drugs are now used, or are potentially useful, to treat patients with spasticity. Although these compounds vary in their actions on spinal neurons and reflex arcs, it is possible to formulate reasonable hypotheses regarding their modes of action. The benzodiazepines bind to specific benzodiazepine receptors linked to classic gamma-aminobutyric acid (GABA) receptors located on the terminals of primary afferent fibers. This binding results in an increased affinity of the GABA receptor for the amino acid, an augmented flux of chloride ions across the terminal membrane, and an increase in the amount of presynaptic inhibition. Baclofen activates GABAB receptors putatively located on the same terminals. Activation of these receptors retards the influx of calcium ions into the terminals, thereby reducing the evoked release of excitatory amino acids and possibly other transmitters. Progabide and its metabolites act on both classic and GABAB receptors. Glycine works on specific inhibitory receptors located on spinal interneurons and motoneurons. The phenothiazines act on the brainstem to alter the function of fusimotor fibers. Phenytoin and carbamazepine reduce the afferent output of muscle spindles. Dantrolene diminishes the activation of the contractile process in muscle fibers by reducing the release of calcium ions from the sarcoplasmic reticulum. This review summarizes the data supporting these concepts.
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PMID:Antispasticity drugs: mechanisms of action. 285 76

Six patients with long-lasting spasticity resistant to different drug therapies including oral baclofen received a bolus injection of lumbar intrathecal baclofen. Electromyographic (EMG) reactions of leg muscles (soleus, tibialis anterior, quadriceps, and hamstrings) to standard stimuli and during attempts at voluntary activation were recorded before the drug injection and up to 3 h after the injection. Responses to joint movements, H-reflexes, ankle clonus, and defensive reactions were noticeably suppressed within 30-45 min after the injection and had practically disappeared after 2 h. Ankle clonus was seen only in patients with H-reflexes, and clonus disappeared when the reflex responses to the n. tibialis stimuli were absent. A decrease in clonus EMG burst amplitudes was accompanied by a decrease in the clonus frequency. These observations favor the autooscillation hypothesis of clonus. Baclofen injection led to improvement in selective voluntary activation of leg muscles in patients with residual motor control. These results suggest that execution of voluntary motor commands in the patients suffered from functionally abnormal spinal circuitry rather than from changes in the descending motor commands. Intrathecal baclofen appears to be an effective way of eliminating increased muscle tone and spasms which can allow for voluntary motor function when it is present.
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PMID:Short-term effects of intrathecal baclofen in spasticity. 291 60

Multiple sclerosis is a chronic, often progressive disease of the central nervous system which can produce visual, sensory, motor, and genitourinary dysfunction. Although there is no cure, many disabling symptoms can be ameliorated. Baclofen is the treatment of choice for spasticity and is usually given in doses of 30 to 80 mg/day, although higher doses may be used. Bladder symptoms in multiple sclerosis generally fall into the categories of failure to store, failure to empty, and mixed types. Most patients can be managed after obtaining a urine culture and sensitivity and post-voiding residual. A variety of anticholinergic agents plus intermittent self-catheterisation is usually the most effective treatment for bladder dysfunction. Prevention of infection is accomplished by urinary acidifiers or low-dose antibiotics. There is no evidence that long term use of corticosteroids has a beneficial effect on the outcome of multiple sclerosis, although they appear to be useful in hastening the recovery time from an acute exacerbation. There are a number of experimental therapeutic agents which are used to modulate the immune response, which may prove to be of use in slowing or arresting the progression of multiple sclerosis.
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PMID:Multiple sclerosis. Current concepts in management. 298 64

Baclofen is used clinically to treat spasticity, but has received little attention as a potential antiepileptic agent. To explore the antiepileptic potential of baclofen further, we tested its effect on stimulus train-induced bursting, an in vitro model of hippocampal epileptiform activity. In hippocampal slices prepared from male rats, extracellular field potentials were recorded in stratum pyramidale of CA3, and electrical stimuli were delivered to s. radiatum of CA3. After stable responses to single stimuli were established, stimulus trains were delivered every 5 min until stable triggered and spontaneous population bursting were elicited. (+/-)-Baclofen was bath-applied to the slices at varying concentrations to study its ability to suppress synaptic transmission and epileptiform activity. EC50 values for suppression of orthodromic population spike amplitude, of triggered burst duration and of spontaneous burst frequency were 2300, 355 and 26.9 nM, respectively; all statistically significantly different. These findings suggest that baclofen suppresses epileptiform electrical activity in the hippocampus at concentrations well below those which suppress normal synaptic transmission, and support renewed consideration of baclofen as an antiepileptic agent.
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PMID:Baclofen suppresses hippocampal epileptiform activity at low concentrations without suppressing synaptic transmission. 301 73


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