lioresal 5 mg
The two different baclofen 10-mg formulations had similar PK profiles and were bioequivalent based on Cmax and AUClast.
lioresal drug classifications
To determine whether gamma-aminobutyric acid (GABA) affects the contractile properties of airway smooth muscle and, if so, what the mechanism of action is, the authors studied guinea pig tracheal rings under isometric conditions in vitro. GABA and related substances, baclofen and muscimol, had no effect on the resting tension but reversibly depressed contractions induced by electrical field stimulation in a dose-dependent fashion, IC50 values (mean +/- S.E.) being 5.6 +/- 1.4 X 10(-6) M, 6.8 +/- 0.9 X 10(-6) M and 8.5 +/- 1.5 X 10(-5) M, respectively. In contrast, GABA did not alter the response to exogenous acetylcholine or the nonadrenergic noncholinergic inhibitory component. Pretreatment of tissues with bicuculline antagonized the inhibitory effect of GABA as well as that of baclofen. This inhibitory effect was not modified by propranolol, phentolamine, hemicholinium-3 or naloxone, but it was blocked by the Cl channel blocker furosemide and by the substitution of external Cl. These results suggest that GABA decreases the contractile response of airway smooth muscle to cholinergic nerve stimulation by inhibiting the evoked release of acetylcholine and that this effect is exerted by activating Cl-dependent, bicuculline-sensitive GABA receptors.
To assess the effect of intrathecal baclofen on spastic dysarthia in cerebral palsy.
The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.
lioresal 3 mg
The cellular mechanisms underlying mu opioid facilitation of mossy fiber (MF) long-term potentiation (LTP) and synaptic transmission were investigated in the rat hippocampal slice. Naloxone (10 microM) significantly inhibited the induction of mossy fiber LTP, an effect attributed by Derrick and Martinez [B.E. Derrick, J.L.J. Martinez, Opioid receptor activation is one factor underlying the frequency dependence of mossy fiber LTP induction, J. Neurosci. 14 (1994) 4359-4367] to antagonism of endogenous opioid peptide action. We found that the inhibitory effects of naloxone were not blocked by bicuculline, suggesting that endogenous opioids did not enhance mossy fiber LTP by depressing GABAA inhibition. [d-Ala2, NMePhe4, Glyol5] enkephalin, DAMGO (300 nM), a mu opioid agonist, mimicked the action of endogenous opioids, enhancing both mossy fiber LTP induction and paired-pulse facilitation. DAMGO potentiation of the paired-pulse facilitation of mossy fiber response was also insensitive to bicuculline but was blocked by the mu selective antagonist CTOP. Further analysis of the cellular mechanism showed that the depletion of internal Ca2+ stores by thapsigargin (1 microM), or inhibition of protein kinases by application of staurosporine (1 microM) did not block the DAMGO facilitation of mossy fiber-CA3 synaptic transmission. However, application of phaclofen (100 microM GABAB receptor antagonist or SCH 50911, a more potent GABAB antagonist significantly inhibited the DAMGO effect (49+/-15%; 51+/-19% inhibition, P<0.05). The data indicate that the DAMGO effect on the mossy fiber pathway is partially mediated by a reduction in GABA activation of GABAB receptors. These findings further suggest that endogenous opioid peptides activate mu opioid receptors to facilitate mossy fiber LTP and synaptic transmission in rat hippocampus partially by GABAB receptor-mediated disinhibitory mechanism.
lioresal generic name
Idiopathic recurrent priapism is a difficult problem to treat and a potentially devastating condition that may result in irreversible penile fibrosis. We present the case of a patient who, during a period of 10 years, had recurrent episodes of idiopathic priapism and we show that therapeutic options do exist for the management.
lioresal 5mg tablet
The effects of alpha 2-adrenoceptor and GABA receptor agonists on citric acid-induced cough and increased tidal volume were investigated in conscious guinea pigs. Inhalation of low doses of B-HT 920 (5-allyl-2-amino 5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine dihydrochloride), and xylazine significantly inhibited citric acid-induced cough and tidal volume increases. Intraperitoneal administration of higher doses of B-HT 920 than those given by aerosol were ineffective. The inhibitory effects of B-HT 920 were antagonised by prior intraperitoneal administration of yohimbine, but not atropine. Inhalation of GABA or baclofen inhibited tidal volume increases, but had no effect on cough. Inhaled alpha 2-adrenoceptor or GABA agonists had no effect on the reduced respiratory rate after citric acid inhalation. It is concluded that alpha 2-adrenoceptor agonists inhibit cough via a mechanism which may not be related to their ability to reduce citric acid-induced tidal volume increases, since GABA and baclofen inhibited tidal volume increases but not cough. We suggest that alpha 2-adrenoceptor agonists may have therapeutic potential in the treatment of cough.
lioresal 50 mg
An expert panel consulted on best practices.
To summarize Cochrane reviews that assess the effectiveness and safety of pharmacological interventions in the treatment of alcohol withdrawal.
lioresal 2 mg
The present study was designed to investigate antinociceptive effect of GABA agonists regarding visceral as well as somatic noxious stimuli. Following the approval by the institutional animal care committee, an intrathecal catheter was implanted in the subarachnoid space at the L 4/5 level in male Sprague-Dawley rats. The tail flick (TF) test and the colorectal distension test (CD) were used to measure responses to somatic and visceral stimuli, respectively. Threshold in TF test and CD test were measured at 5, 10, 15, 20, 30, 60, 90, 120 and 180 min after the intrathecal injection of 0.1, 1, 5, 20 micrograms of muscimol, 0.01, 0.1, 0.3, 1 microgram of baclofen or normal saline. Percent of maximum possible effect (%MPE) and %area under the curve (%AUC) were calculated by transforming response threshold in TF and CD tests. Repeated measure ANOVA followed by Fisher's PLSD test were used for statistical analysis. Muscimol 0.1 microgram increased mean %MPE in TF test at 10 min to 15% but not in CD test. Muscimol 1, 5 and 20 micrograms significantly increased %MPE at 5 min in TF and CD tests. Muscimol 20 micrograms produced 100%MPE for 180 min after drug injection. Baclofen 0.1, 0.3 and 1 microgram significantly increased %MPE at 5 min in TF and CD test. Antinociceptive effect in TF test seems to be greater than that in CD test. Muscimol caused motor disturbance but baclofen did not. It is concluded that intrathecally administered muscimol and baclofen produced somatic and visceral antinociception in a dose dependent fashion.
lioresal intrathecal dosage
Normal aging may limit the signaling efficacy of certain GPCRs by disturbing the function of specific Gα-subunits and leading to deficient modulation of intracellular functions that subserve synaptic plasticity, learning and memory. Evidence suggests that Gαq/₁₁ is more sensitive to the effects of aging relative to other Gα-subunits, including Gαo. To test this hypothesis, the functionality of Gαq/₁₁ and Gαo were compared in the hippocampus of young (6 months) and aged (24 months) F344 × BNF₁ hybrid rats assessed for spatial learning ability. Basal GTPγS-binding to Gαq/₁₁ was significantly elevated in aged rats relative to young and but not reliably associated with spatial learning. mAChR stimulation of Gαq/₁₁ with oxotremorine-M produced equivocal GTPγS-binding between age groups although values tended to be lower in the aged hippocampus and were inversely related to basal activity. Downstream Gαq/₁₁ function was measured in hippocampal subregion CA₁ by determining changes in [Ca(2+)]i after mAChR and mGluR (DHPG) stimulation. mAChR-stimulated peak change in [Ca(2+)]i was lower in aged CA₁ relative to young while mGluR-mediated integrated [Ca(2+)]i responses tended to be larger in aged. GPCR modulation of [Ca(2+)]i was observed to depend on intracellular stores to a greater degree in aged than young. In contrast, measures of Gαo-mediated GTPγS-binding were stable across age, including basal, mAChR-, GABABR (baclofen)-stimulated levels. Overall, the data indicate that aging selectively modulates the activity of Gαq/₁₁ within the hippocampus leading to deficient modulation of [Ca(2+)]i following stimulation of mAChRs but these changes are not related to spatial learning.
Anesthetized pigs were instrumented with eight intrathecal microdialysis probes placed at multiple points along the neuroaxis in both the anterior and posterior intrathecal space to permit continuous CSF sampling for measurement of bupivacaine and baclofen concentrations. Animals were divided into three groups and received bupivacaine and baclofen infusions at 20 or 1,000 microl/h or as a 1,000-microl bolus over 5 min every hour. Drug administration continued for 8 h, at which time the animals were killed, and the spinal cord was removed and divided into 1-cm-long sections that were further divided into anterior and posterior portions for measurement of bupivacaine and baclofen concentrations.
lioresal 30 mg
Baclofen, predominantly excreted by the kidneys is accumulated in patients with renal insufficiency leading to the central nervous system toxicity. Here the author reports a patient with end-stage renal disease on maintenance hemodialysis (HD) who developed drowsiness and became unresponsive within a day after taking single 10 mg dose of baclofen. Patient improved completely after two sessions of HD.
To evaluate the effectiveness and safety of baclofen in the treatment of withdrawal syndrome and/or SUDs, providing (1) an outline of its pharmacological features; (2) a summary of studies that have suggested its possible effectiveness in the treatment of SUDs, and (3) a review of randomized, controlled trials (RCTs) on baclofen and SUDs.
These data increase the possibility that GIRK2 channel function plays a major role in the genesis of infantile spasms.
lioresal en alcohol
Sprague-Dawley rats were trained to self-administer propofol at a dose of 1.7 mg/kg per infusion under a fixed ratio (FR1) schedule of reinforcement for 14 d. In a separate set of experiments, food-maintained self-administration under a fixed ratio (FR5) schedule and locomotor activities of Sprague-Dawley rats were examined.
lioresal y alcohol
To assess the need for orthopedic surgery of the lower extremities in such cases, the authors retrospectively reviewed the outcome in 48 patients with spastic CP who were treated with IBI.
lioresal 10 mg
To review all pharmacological and physiological data available on intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice and future research.
lioresal drug interactions
In vivo microdialysis was used to investigate the role of serotonin in the locomotor hyperactivity produced by injections of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), muscimol and baclofen into the median raphe nucleus (MR) of unanesthetized rats. Intra-MR injections of the GABA(A) agonist muscimol (25 ng) resulted in a pronounced increase in locomotor activity which was accompanied by a 42% decrease in hippocampal serotonin release during the first hour following injection. Intra-MR injections of the GABA(B) agonist baclofen (125 ng) induced hyperactivity of a similar magnitude, but failed to affect hippocampal serotonin release. In contrast, the serotonin (5-HT1A) agonist 8-OHDPAT (5 microg) produced only a small effect on locomotor activity but reduced hippocampal serotonin output by 51%. These findings demonstrate that it is possible to dissociate the effects of intra-MR drug injections on locomotor activity and hippocampal 5-HT release and strongly support the view that nonserotonergic neurons in the paramedian tegmentum are importantly involved in the control of behavioral arousal.
lioresal tablets 10mg
To determine if baclofen is an effective measure for prophylaxis and treatment of alcohol withdrawal in high risk populations upon admission to hospital wards. Design, Setting, Patients - Retrospective chart review of 42 inpatients at St. Anthony Hospital from November 2004 to April 2005. Patients were included if they were determined to be at risk for alcohol withdrawal. Patients were then divided into categories of prophylactic success versus failure and treatement success versus failure based on DSM-IV criteria for alcohol withdrawal.
lioresal overdose treatment
Long-term continuous intrathecal baclofen (CITB) infusion is a treatment option used to manage otherwise intractable spasticity and is delivered via an implantable pump. The purpose of this single-center multidisciplinary review was to report on the long-term safety and efficacy of CITB in the treatment of 21 children with intractable severe spasticity of cerebral origin. Nineteen recipients had spastic quadriplegia and two had spastic diplegia. Seven recipients had level IV severity on the Gross Motor Functional Classification System and 14 had level V. Median age at implantation was 12 years (range 4 to 20). Fifteen recipients were male, 6 were female. Seventeen recipients were alive at the end of the follow-up period (31 to 78 months; mean 53, SD 4). The Ashworth scale showed a substantial decrease in spasticity in the upper and lower extremities at 6 months and at the most recent follow-up. The Gross Motor Function Measure and Pediatric Evaluation of Disability Inventory showed no functional change. Most treatment goals were at least partly achieved. Caregivers reported a reduction in use of oral medication for spasticity, and improvements in comfort, function, and ease of care. Caregiver satisfaction was high. During 80 recipient-years of pump operation, 153 treatment-associated adverse events occurred: 27 of these were device-related. There were four deaths unrelated to CITE, including one from acute pancreatitis. Our findings might assist in establishing patient selection criteria and treatment goals, improving patient follow-up, and monitoring adverse events.
The relationship between neuropeptides and serotonergic neurones was investigated in rat spinal cord, in vivo, using a subarachnoidal perfusion technique. The 5-hydroxytryptamine (5-HT) release from the spinal cord could be evoked by substance P and peripheral pain stimulation (tail pinch), but not by methionine-enkephalin (met-EK). The substance P-evoked 5-HT release was slightly potentiated by met-EK. The tail pinch-evoked 5-HT release was inhibited by met-EK and baclofen, but potentiated by naloxone. These findings may infer a possible mechanism by which neuroactive peptides regulate 5-HT release from serotonergic neurones in the spinal cord.
lioresal maximum dose
This study presents a 52-year-old man with tetraplegia after a brainstem stroke. Four days after the placement of a Synchromed II infusion pump (100 mcg per day), the patient presented a paralytic ileus. The treatment was conservative and the dosage of intrathecal baclofen was reduced to lowest drug flow. After 15 days of treatment the ileus was resolved and the dosage progressively increased without incident.