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At least 19 recordsLinked to original sources
PubMed2003

Baclofen withdrawal following removal of an intrathecal baclofen pump despite oral baclofen replacement.

Intrathecal baclofen is used as a muscle relaxant and antispasmodic in cases of spasticity resulting from central nervous system trauma. The baclofen withdrawal syndrome may include hyperthermia, tachycardia, hypertension, seizures, altered mental status, and psychomotor agitation. We report a case in which the removal of a baclofen pump lead tothe development of severe withdrawal symptoms despite oral baclofen replacement therapy. In order to avoid the development of withdrawal, adequate doses of GABA agonist agents should be administered immediately prior to, and following, baclofen pump removal.

Adult↗
PubMed1984

D-Baclofen: is it an antagonist at baclofen receptors?

Following intrathecal administration into the spinal subarachnoid space, baclofen produced dose related increases in tail flick latency. L-Baclofen was twice as potent as the DL-racemate and 100 times more potent than D-baclofen. When D-baclofen was injected intrathecally 15 min prior to L-baclofen, the subsequent effect of L-baclofen was markedly reduced. This reduction was dose-related for D-baclofen in doses at least 20 times the L-baclofen dose. D-baclofen administered concomitantly with L-baclofen only slightly increased the effect of L-baclofen. Pretreatment with D-baclofen (up to 10 times the dose of L-baclofen) did not inhibit the effect of L-baclofen when drugs were injected intraperitoneally. These results indicate that D-baclofen can antagonize the antinociceptive effect of L-baclofen following intrathecal administration. D-Baclofen should prove to be a useful tool for investigation of the role of stereoselective baclofen receptors in a variety of pharmacological processes.

Analgesics↗
PubMed1991

Effects of phaclofen and the enantiomers of baclofen on cardiovascular responses to intrathecal administration of L- and D-baclofen in the rat.

In a previous study it was found that i.t. administration of L-baclofen decreased arterial pressure and heart rate while D-baclofen differentially increased arterial pressure. The objective of the present study was to determine which of these effects was blocked by prior administration of the GABAB receptor antagonist, phaclofen, and whether the effect of one enantiomer of baclofen could be blocked by prior administration of the other. The decreases in systolic and diastolic arterial pressures and in heart rate produced by i.t. administration of 70 nmol of L-baclofen were unaffected by i.t. administration of 7, 70 or 700 nmol of D-baclofen 10 min prior to administration of L-baclofen, but were blocked by administration of 5 mumol of phaclofen given 3-5 min prior to L-baclofen. On the other hand, the increases in systolic and diastolic arterial pressures induced by i.t. administration of 700 nmol of D-baclofen were blocked by 70 nmol but not by 7 nmol of L-baclofen, as well as by 2.5 mumol of phaclofen; the effect of L-baclofen cannot be attributed to a desensitization of D-baclofen-sensitive receptors as two successive doses of D-baclofen given 7 min apart had quantitatively similar effects. Phaclofen alone increased systolic and diastolic arterial pressures and heart rate. The results are interpreted as indicating that D-baclofen is not an antagonist of L-baclofen in this paradigm; rather, they suggest that L-baclofen reduces the effects of D-baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

D-Baclofen is an antagonist at baclofen receptors mediating antinociception in the spinal cord.

The antagonistic action of D-baclofen at baclofen receptors mediating antinociception in the spinal cord was examined. Drugs were administered intrathecally to rats and effects on nociceptive threshold evaluated in the tail flick test. L-Baclofen, D-baclofen and the racemate produced dose-related increases in tail flick latency, with L-baclofen being twice as potent as the racemate and approximately 100 times more potent than D-baclofen. When D-baclofen was injected 15 min prior to L-baclofen, it produced a dose-related inhibition of the effect of L-baclofen. Concomitant administration produced a more ambiguous effect. Antagonism appeared specific for baclofen receptors because analogues with full and partial agonist activity as well as an agonist dose of D-baclofen, but not morphine or noradrenaline, were inhibited by pretreatment with D-baclofen. gamma-Aminobutyric acid (GABA) did not increase tail flick latency either alone or following pretreatment with an uptake inhibitor or a GABA-transaminase inhibitor. Antinociception produced by intrathecal administration of Baclofen appears to result from activation of a receptor which is stereoselective for the L-isomer and can be blocked by D-baclofen in doses which have initial agonist activity. This receptor may not be a GABA subtype because GABA does not mimic the effect of baclofen and the rank order of potency of analogues differs from established GABAB systems.

Alkynes↗
PubMed2004

Intrathecal baclofen withdrawal syndrome- a life-threatening complication of baclofen pump: a case report.

BACKGROUND: Intrathecal baclofen pump has been used effectively with increasing frequency in patients with severe spasticity, particularly for those patients who are unresponsive to conservative pharmacotherapy or develop intolerable side effects at therapeutic doses of oral baclofen. Drowsiness, nausea, headache, muscle weakness, light-headedness and return of pretreatment spasticity can be caused by intrathecal pump delivering an incorrect dose of baclofen. Intrathecal baclofen withdrawal syndrome is a very rare, potentially life-threatening complication of baclofen pump caused by an abrupt cessation of intrathecal baclofen. CASE PRESENTATION: A 24-year-old man with a past medical history of cerebral palsy and spastic quadriparesis developed hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, acute renal failure and multisystem organ failure leading to a full-blown intrathecal baclofen withdrawal syndrome. Intrathecal baclofen pump analysis revealed that it was stopped due to some programming error. He was treated effectively with supportive care, high-dose benzodiazepines and reinstitution of baclofen pump. CONCLUSION: The episodes of intrathecal baclofen withdrawal syndrome are mostly caused by preventable human errors or pump malfunction. Educating patients and their caregivers about the syndrome, and regular check-up of baclofen pump may decrease the incidence of intrathecal baclofen withdrawal syndrome. Oral baclofen replacement may not be an effective method to treat or prevent intrathecal baclofen withdrawal syndrome. Management includes an early recognition of syndrome, proper intensive care management, high-dose benzodiazepines and prompt analysis of intrathecal pump with reinstitution of baclofen.

Adult↗
PubMed1986

D-baclofen does not antagonize the actions of L-baclofen on rat neocortical neurons in vitro.

The ability of D-baclofen to antagonize the actions of L-baclofen on rat neocortical neurons was investigated. Intracellular recordings were made from neurons in cortical layers 2 and 3 in an in vitro slice preparation. Baclofen stereoisomers were applied at known concentrations in the superfusion medium. At a concentration of 3 microM, L-baclofen produced approximately 70% depressions of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) that were evoked by stimulation of superficial cortical layers. L-baclofen also hyperpolarized neocortical neurons. These hyperpolarizations were accompanied by decreases in neuronal input resistance and in direct excitability. We have shown previously that these latter effects are secondary to the action of baclofen to increase the potassium conductance of neocortical neurons. D-baclofen, at concentrations of 1-100 microM, did not antagonize depressions by L-baclofen of EPSPs and IPSPs nor the action of L-baclofen to increase the potassium conductance of neocortical neurons. At concentrations of 50-100 microM, D-baclofen produced 20-30% effects when applied alone, thus suggesting that these concentrations of D-baclofen produced a significant degree of receptor occupancy. Our results demonstrate that D-baclofen is not an antagonist or high affinity partial agonist at the receptors through which baclofen exerts its effects on single neurons in the rat neocortex.

Animals↗
PubMed1990

Effects of D-baclofen and L-baclofen on the trigeminal nucleus.

D-Baclofen reduced the response to L-baclofen in the feline trigeminal nucleus, the spinal cord of the rat and in patients with trigeminal neuralgia, but not in slices of hippocampus or neocortex. The iontophoretic application of 10-20 nA L-baclofen depressed excitatory transmission in the trigeminal nucleus oralis, similar to the effect of 0.1-0.4 mg/kg L-baclofen, given intravenously. The concomitant iontophoresis of 10-20 nA D-baclofen reduced the effect of iontophoretically applied L-baclofen. However, larger doses of D-baclofen (30-60 nA) did not, while still larger doses (200-400 nA) by themselves depressed response of the neuron, similar to the action of small doses of L-baclofen. The iontophoresis of 30-40 nA L-baclofen had a stronger effect than that previously obtained with systemic administration and D-baclofen was not able to block it. These observations suggest that D-baclofen is a partial agonist at the GABAB receptor. Failure to observe a blocking effect of D-baclofen in slices of hippocampus or neocortex could be due to the larger doses used or to a difference in receptor types. The observations emphasise the need to test drugs at therapeutic concentrations in an appropriate model, in order to predict reliably their therapeutic actions.

Animals↗
PubMed1987

Comparison of L-baclofen and racemic baclofen in trigeminal neuralgia.

L-Baclofen was compared with racemic baclofen (Lioresal) in a double-blind crossover trial in 15 patients with typical trigeminal neuralgia. L-Baclofen was more effective than five times as much racemic baclofen in nine patients. Six of these nine patients have continued pain-free on L-baclofen for 4 to 17 months (mean, 10 months). L-Baclofen was much better tolerated than racemic baclofen. Our results suggest that L-baclofen represents a significant improvement over racemic baclofen in the treatment of trigeminal neuralgia, and support our laboratory observations indicating that D-baclofen antagonizes the action of L-baclofen.

Adult↗
PubMed2002

Evidence of tolerance to baclofen in treatment of severe spasticity with intrathecal baclofen.

In a retrospective study, changes in baclofen dose and complication frequency were recorded in 79 patients with intrathecal baclofen administration and the effect on nightly muscle spasms was measured over a mean observation period of 34 months, during which time an increase in the daily dose of baclofen during the first 1--1-1/2 years is notified. On subsequent pump fillings the daily dose of baclofen remained stable in the group of non-multiple sclerosis patients. In contrast, the group of multiple sclerosis patients showed a steady increase in their daily dose of baclofen. We found a frequency of complications of 0.014 monthly often due to catheter problems. There was a significant decrease in numbers of nightly muscle spasms in an 8 h recording period from 77+/-20 preoperatively and 9+/-3 (P=0.02) 3 months after surgery. The steady increase in the daily dose of baclofen in order to obtain adequate reduction in spasticity and nightly muscle spasms in the first 1--1-1/2 years cannot fully be explained by caution and difficulties in achieving the correct dose, but also indicates that tolerance to baclofen occurs. Complications are often due to infection or catheter problems.

Adult↗
PubMed1995

Effects of L-baclofen and D-baclofen on the auditory system: a study of click-evoked potentials from the inferior colliculus in the rat.

The drug baclofen is a potential treatment for severe tinnitus, but its action in relieving tinnitus is not known. Baclofen is available as an approved drug only in racemic form with about equal content of the two enantiomers. In the present paper we show that L-baclofen causes a considerable (40.7%) suppression of the amplitude of the second peak in the click-evoked response from the cochlear nucleus. Bipolar recordings from the external nucleus of the inferior colliculus showed that L-baclofen caused a reduction in the amplitude of three or four distinct peaks in this response. D-Baclofen had no detectable effect on the response from the cochlear nucleus, and had only a slight effect on one component of the response from the external nucleus of the inferior colliculus. The demonstrated effect of L-baclofen on excitation in the ascending auditory pathway indicates that this drug may be a potential treatment for hyperactive auditory disorders such as tinnitus and hyperacusis.

Animals↗
PubMed2004

Efficacy of intrathecal morphine in the treatment of baclofen tolerance in a patient on intrathecal baclofen therapy (ITB).

STUDY DESIGN: Case report. OBJECTIVES: A case report of tolerance to intrathecal baclofen therapy (ITB) treated with intrathecal morphine ('baclofen holiday'). SETTING: Institut Guttmann, Neurorehabilitation Hospital of Barcelona, Spain. CASE REPORT: A 30-year-old female patient is described with incomplete paraplegia below T6 on the left side and below T8 on the right side, ASIA B, caused by trauma occurring 12 years previously, in whom an intrathecal system had been implanted for baclofen infusion 10 years ago. The patient showed tolerance to baclofen therapy and was treated with intrathecal morphine infusion for 2 weeks. Baclofen infusion resulted in adequate control of spasticity.

Adult↗
PubMed1985

Baclofen versus diazepam for the treatment of spasticity and long-term follow-up of baclofen therapy.

Baclofen (25 to 60 mg per day) and diazepam (10 to 40 mg per day) were evaluated for spasticity reduction in a double-blind, crossover study in 13 patients over a period of 19 weeks. Both drugs produced overall improvement and there was no significant difference in preference for one or other treatment. Side-effects, especially excessive daytime sedation, were more common in the diazepam group. In a companion baclofen long-term study, 18 spastic patients were treated with baclofen for an average of 4 years. Baclofen discontinuation in this group resulted in a worsening of spastic signs and symptoms in 16 patients, with no evidence of drug tolerance even after many years of baclofen therapy.

Adult↗
PubMed2004

Baclofen toxicity in an 8-year-old with an intrathecal baclofen pump.

Baclofen delivered by intrathecal pumps (ITB) is increasingly being utilized in the pediatric population, however, resources and education to support problems with these devices are limited. Typical management strategies for systemic baclofen overdose include removal of baclofen from the device reservoir or removal of cerebrospinal fluid from the adjacent device catheter. Appropriate care of these patients requires awareness of the clinical patterns of toxicity and mechanics of the ITB pump delivery system. This report describes the clinical presentation, unfamiliar dilemmas, and the management of a pediatric patient with intrathecal baclofen toxicity, noting problems that may arise in the care of these patients.

Baclofen↗
PubMed1989

Determination of baclofen and alpha-baclofen in rat liver homogenate and human urine using solid-phase extraction, o-phthalaldehyde-tert.-butyl thiol derivatization and high-performance liquid chromatography with amperometric detection.

Methods were developed for the determination of the zwitterionic compounds baclofen and alpha-baclofen in complex biological samples (rat liver homogenates and human urine) in concentration ranges that would be suitable for pharmacokinetic studies of these compounds. In the procedure, the biological samples along with an internal standard were selectively concentrated using C18 solid-phase extraction cartridges, evaporated, derivatized with o-phthalaldehyde and tert.-butyl thiol at room temperature for 2 min, then subjected to high-performance liquid chromatographic analysis. The reversed-phase (C18) chromatographic analysis with amperometric detection (glassy carbon electrode in oxidative mode, +0.6 V vs. Ag/AgCl) was found to be useful for the measurement of both baclofen and alpha-baclofen from 10 ng/ml to 10 micrograms/ml in these complex biological samples. The primary advantage of the method was that the derivatives formed using tert.-butyl thiol were markedly more stable than the previously reported derivatives prepared using mercaptoethanol.

Animals↗
PubMed1999

Plasma baclofen levels in children receiving continuous intrathecal baclofen infusion.

To determine the plasma baclofen concentrations of children undergoing continuous intrathecal baclofen infusion for treatment of cerebral spasticity, we assayed plasma samples from six children, 8 to 18 years of age, who were receiving intrathecal baclofen at constant rates of 77 to 400 micrograms/day. Plasma levels were at or below the limit of quantification (10 ng/mL) in all patients.

Administration, Oral↗
PubMed1978

[Quipazine antagonizing baclofen activity. Influence of baclofen and gamma-hydroxybutyric acid on serotonin metabolism in rat brain (author's transl)].

Baclofen increases the concentration of serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) in the rat c. striatum without causing concomitant increase in 5-HT biosynthesis. The effect of baclofen on 5-HIAA, but not that on 5-HT, was antagonized dose-dependently by quipazine. It is assumed that quipazine acts by stimulating 5-HT autoreceptors.

Aminobutyrates↗