baclofen

Spasticity is a potentially debilitating symptom of various acquired and congenital neurologic pathologies that, without adequate treatment, may lead to long-term disability, compromise functional independence, and negatively impact mental health. Several conservative as well as non-nerve targeted surgical strategies have been developed for the treatment of spasticity, but these may be associated with significant drawbacks, such as adverse side effects to medication, device dependence on intrathecal baclofen pumps, and inadequate relief with tendon-based procedures...

BACKGROUND: Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). AIMS/METHODS: This study, conducted in 30 healthy volunteers, examined the acute effects of GABAA (lorazepam: 1 mg) and GABAB receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety...

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INTRODUCTION: The stiff person syndrome (SPS) is a rare and disabling neurological disorder characterized by muscle stiffness, painful spasms and rigidity involving the proximal and axial limb muscles, with an estimated incidence of 1 case per million per year. The first line of treatment for symptomatic management includes gamma-aminobutyric acid (GABA)ergic agonists, benzodiazepines and baclofen. The therapeutic plasma exchange (TPE), alone or as an adjuvant to other forms of immunomodulation, has been used as a therapeutic option, particularly in refractory cases...

Background: Intrathecal baclofen (ITB) is used for the treatment of intractable spasticity. The burden of traveling for ITB screening and aftercare is problematic for nursing home residents with severe spasticity and seems to result in undertreatment of spasticity. The aim of this study is to evaluate the effectiveness, safety, and feasibility of ITB for nursing home residents treated in their home, describing the selection phase, the initial trial of ITB, and aftercare up to 3 months after implantation of an ITB pump...

INTRODUCTION: Alcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their communities and society at large. Even though pharmacotherapy is an integral part of AUD treatment, the few available substances show limited efficacy and limited clinical impact. Thus, there is a need for new innovative pharmacotherapeutic approaches. AREAS COVERED: This paper provides a comprehensive review of drugs approved for the treatment of AUD as well as those currently in phase II and III development...

The programmed death-ligand 1 (PD-L1) on the surface of tumor cells binds to the receptor programmed cell death protein 1 (PD-1) on effector T cells, thereby inhibiting the anti-tumor immune response. Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has been approved for the treatment of human cancers with lasting clinical benefit. However, many cancer patients did not respond to anti-PD-1/PD-L1 antibody blocking therapy or drugs targeting PD-1/PD-L1. Recent studies have shown that the response to PD-1/PD-L1 blockade may be related to the PD-L1 abundance of tumor cells...

Although intrathecal baclofen injections have been used for spasticity management regarding stroke, spinal cord injury, and central nervous system diseases, their relative efficacy is controversial. This systematic review scoured 3 multinational electronic databases (Cochrane Library, MEDLINE, and Embase) to isolate relevant studies. We analyzed non-randomized studies and randomized control trials (RCTs) with direct comparisons against other spasticity management interventions for adult stroke patients. Risk of Bias (RoB) and the Risk of Bias Assessment tool for Non-randomized Studies evaluations were implemented with Cochrane's RoB tool...

BACKGROUND: Positive allosteric modulators (PAMs) of the GABAB receptor constitute a new class of GABAB-receptor ligands. GABAB PAMs reproduce several pharmacological effects of the orthosteric GABAB receptor agonist, baclofen, although displaying a better safety profile. AIMS: This paper reviews the reducing or, frequently, even suppressing effects of all GABAB PAMs tested to date on multiple alcohol-related behaviours in laboratory rodents exposed to validated experimental models of human alcohol use disorder...

BACKGROUND: Management of medically refractory limb-specific hypertonia is challenging. Neurosurgical options include deep brain stimulation, intrathecal baclofen, thalamotomy, pallidotomy, or rhizotomy. Cervical dorsal rhizotomy has been successful in the treatment of upper-extremity spasticity. Cervical ventral and cervical ventral-dorsal rhizotomy (VDR) has been used in the treatment or torticollis and traumatic hypertonia; however, the use of cervicothoracic VDR for the treatment of upper-extremity mixed hypertonia is not well described...

The target of alcohol's effect on the central nervous system has been sought for more than 50 years in the brain's GABA system. The behavioral and emotional effects of alcohol in humans and rodents are very similar to those of barbiturates and benzodiazepines, and GABAA receptors have been shown to be one of the sites of alcohol action. The mechanisms of GABAergic inhibition have been a hotspot of research but have turned out to be complex and controversial. Genetics support the involvement of some GABAA receptor subunits in the development of alcohol dependence and in alcohol use disorders (AUD)...

New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options for opioid and nicotine use disorders. So far, there has been little attention to substitution therapy for the treatment of AD. Here, we explain the mechanistic foundations of alcohol substitution maintenance therapy. Alcohol has many primary targets in the brain (and other organs) and the physical interaction of ethanol molecules with these specific ethanol-sensitive sites on a variety of ionotropic receptors (e...

Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally...

PURPOSE: The use of intrathecal medications for the management of spasticity and various pain syndromes in the adult population has been previously reported. However, no evidence-based guidelines currently exist in the pediatric population. This case series presents patients (n = 8) with pediatric-onset disability who underwent placement of intrathecal baclofen pumps initially for management of severe spasticity. Despite titration of dose and use of oral analgesia, their uncontrolled pain persisted...

INTRODUCTION: Morphine induces ovarian cysts that cause obesity and disrupt sex hormone secretion. Baclofen, a gamma-aminobutyric acid receptor agonist, can help regulate sex hormones and reduce harmful blood lipids by protecting against morphine-induced gamma-aminobutyric acid inhibition. We investigated the prophylactic effect of baclofen in rats receiving morphine by comparing with the untreated groups. MATERIALS AND METHODS: Forty eight female Wistar rats were randomly divided into several groups, including control (saline 1 mL/kg, i...

BACKGROUND AND OBJECTIVES: Intrathecal baclofen (ITB) for severe spasticity can encounter complications such as wound dehiscence and ulcers because of elevated intracompartmental pressure within the abdominal subcutaneous and subfascial pocket housing the pump. We propose an innovative technique to manage ITB wound ulcers. METHODS: Resecting the umbilicus create a more spacious and less tension-prone pocket for the ITB pump. RESULTS: Between 2015 and 2023, we implanted ITB pumps in 65 patients...

BACKGROUND: Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023 American Geriatrics Society Beers Criteria® for potentially inappropriate medication use in older adults. In our geriatric practice, off-label use of tizanidine as preemptive analgesia drove us to find recent advances in its pharmacology and therapeutics. An update review of tizanidine was thus presented, aiming to bring the latest knowledge to clinicians and promote further research and practical exploration...

Evidence indicates that the anterior (aIC), but not posterior (pIC), insular cortex promotes cued reinstatement of cocaine seeking after extinction in rats. It is unknown whether these subregions also regulate heroin seeking and whether such involvement depends on prior extinction learning. To address these questions, we used baclofen and muscimol (BM) to inactivate the aIC or pIC bilaterally during a seeking test after extinction or prolonged withdrawal from heroin. Male Sprague-Dawley rats in the extinction groups underwent 10+ days of heroin self-administration, followed by 6+ days of extinction sessions, and subsequent cued or heroin-primed reinstatement...

Paroxysmal positional nystagmus frequently occurs in lesions involving the cerebellum, and has been ascribed to disinhibition and enhanced canal signals during positioning due to cerebellar dysfunction. This study aims to elucidate the mechanism of central positional nystagmus (CPN) by determining the effects of baclofen on the intensity of paroxysmal positional downbeat nystagmus due to central lesions. Fifteen patients with paroxysmal downbeat CPN were subjected to manual straight head-hanging before administration of baclofen, while taking baclofen 30 mg per day for at least one week, and two weeks after discontinuation of baclofen...

GABA (γ-amino butyric acid) analogues like baclofen, tolibut, phenibut, etc., are well-known GABAB1 inhibitors and pharmaceutically important drugs. However, there is a huge demand for more chiral GABA aryl analogues with promising pharmacological actions. Here, we demonstrate the chiral ligand acetyl-protected amino quinoline (APAQ) mediated enantioselective synthesis of GABAB1 inhibitor drug scaffolds from easily accessible GABA via Pd-catalyzed C(sp3)-H activation. The synthetic methodology shows moderate to good yields, up to 74% of ee...