Baclofen: Therapeutic Use and Potential of the Prototypic GABAB Receptor Agonist

Bowery, Norman G.

doi:10.1007/978-3-319-46044-4_17

Cited by 12 publications

(5 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The prototypic GABA B receptor agonist Baclofen is currently the only marketed drug targeting GABA B receptors. Numerous studies have reported that the Baclofen and other GABA B receptor agonists impair cognition in animal models [174] . However, these results are not consistent.…”

Section: Gaba B Receptor Agonistsmentioning

confidence: 99%

“…However, these results are not consistent. Baclofen can ameliorate the recognition memory impairment induced by methamphetamine [175] and the spatial working memory deficits induced by chronic cerebral hypoperfusion in rats [176] (for a more comprehensive review, see [174] ). More studies need to be conducted to confirm the effects of Baclofen on cognition.…”

Section: Gaba B Receptor Agonistsmentioning

confidence: 99%

See 1 more Smart Citation

GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia

Wong

2018

Acta Pharmacol Sin

102

View full text Add to dashboard Cite

Schizophrenia is considered primarily as a cognitive disorder. However, functional outcomes in schizophrenia are limited by the lack of effective pharmacological and psychosocial interventions for cognitive impairment. GABA (gamma-aminobutyric acid) interneurons are the main inhibitory neurons in the central nervous system (CNS), and they play a critical role in a variety of pathophysiological processes including modulation of cortical and hippocampal neural circuitry and activity, cognitive function-related neural oscillations (eg, gamma oscillations) and information integration and processing. Dysfunctional GABA interneuron activity can disrupt the excitatory/inhibitory (E/I) balance in the cortex, which could represent a core pathophysiological mechanism underlying cognitive dysfunction in schizophrenia. Recent research suggests that selective modulation of the GABAergic system is a promising intervention for the treatment of schizophrenia-associated cognitive defects. In this review, we summarized evidence from postmortem and animal studies for abnormal GABAergic neurotransmission in schizophrenia, and how altered GABA interneurons could disrupt neuronal oscillations. Next, we systemically reviewed a variety of up-to-date subtype-selective agonists, antagonists, positive and negative allosteric modulators (including dual allosteric modulators) for α5/α3/α2 GABA and GABA receptors, and summarized their pro-cognitive effects in animal behavioral tests and clinical trials. Finally, we also discuss various representative histone deacetylases (HDAC) inhibitors that target GABA system through epigenetic modulations, GABA prodrug and presynaptic GABA transporter inhibitors. This review provides important information on current potential GABA-associated therapies and future insights for development of more effective treatments.

show abstract

Section: Gaba B Receptor Agonistsmentioning

confidence: 99%

Section: Gaba B Receptor Agonistsmentioning

confidence: 99%

GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia

Wong

2018

Acta Pharmacol Sin

102

View full text Add to dashboard Cite

show abstract

“…This fact led us to consider cervical-dorsal muscular spasticity or muscle contracture as an additional component of pain crisis. [ 54 , 55 ].…”

Section: Physiopathologymentioning

confidence: 99%

Perioperative opioid-minimization approach as a useful protocol in the management of patients with Ehlers–Danlos syndrome-hypermobility type, craniocervical instability and severe chronic pain who are to undergo occipito-cervical fixation

Ramírez-Paesano¹,

Clarens²,

Segovia³

et al. 2023

Orphanet J Rare Dis

View full text Add to dashboard Cite

Patients suffering from connective tissue disorders like Ehlers–Danlos syndrome hypermobility type/joint hypermobility syndrome (EDS-HT/JHS) may be affected by craniocervical instability (CCI). These patients experience myalgic encephalomyelitis, chronic fatigue, depression, extreme occipital-cervical pain, and severe widespread pain that is difficult to relieve with opioids. This complex and painful condition can be explained by the development of chronic neuroinflammation, opioid-induced hyperalgesia, and central sensitization. Given the challenges in treating such severe physical pain, we evaluated all the analgesic methods previously used in the perioperative setting, and updated information was presented. It covers important physiopathological aspects for the perioperative care of patients with EDS-HT/JHS and CCI undergoing occipital-cervical/thoracic fixation/fusion. Moreover, a change of paradigm from the current opioid-based management of anesthesia/analgesia in these patients to the perioperative opioid minimization strategies used by the authors was analyzed and proposed as follow-up considerations from our previous case series. These strategies are based on total-intravenous opioid-free anesthesia, multimodal analgesia, and a postoperative combination of anti-hyperalgesic coadjuvants (lidocaine, ketamine, and dexmedetomidine) with an opioid-sparing effect.

show abstract

“…Gabapentine mediates its action through GABA B and facilitates the chloride ions in the Nucleus Accumbens (NAc), ventral palladium (VP), bed nucleus of the stria terminals (BNST), and amygdala (AMY), thereby reducing alcohol-seeking behaviour [15]. Similarly, baclofen, a GABA B agonist, suppresses alcoholstimulated dopamine release in the mesolimbic dopamine system and reduces alcohol drinking behaviour [16]. Further, topiramate and acamprosate antagonize the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor and act as modest GABA A agonists, acting on the calcium-dependent mechanism of alcohol reward and ultimately antagonizing alcohol-induced reward effects [17].…”

Section: Gabaergic System and Drugs Acting On Itmentioning

confidence: 99%

“…Also acts via inhibition of 'T' type calcium current. It also alters the concentration of γ-glutamyl-transferase which is a measure of alcohol consumption [97] Open-label study as per DSM-IV demonstrated that, zonisamide treatment cause significant improvement in the visual analogue scale for craving severity scores and weekly drink consumption in 22 outpatients [98] Muscles fatigue, somnolence, dizziness and ataxia [98] Pregabalin (Maximum 450 mg/day) Newer congener of gabapentin Pregabalin is selectively binds to the α2 subunit of voltagegated calcium channels and inhibits the release of excitatory neurotransmitters [99] In the open-label trial, treatment with pregbalin caused a significant progressive reduction of both craving and withdrawal symptomatology in 20 patients compared to placebo [100] Rashes, allergic reactions Baclofen (30-180 mg/day) Centrally acting muscle relaxant, reduces the acquisition of alcoholdrinking behaviour A selective GABA B receptor agonist, voltage-gated N-type calcium channel blocker and also acts as a suppressor of alcohol-stimulated dopamine release in the mesolimbic dopamine system probable mechanism in the treatment of AUD [101] In preclinical studies treatment with baclofen showed dose-dependent reduction in the self-administered alcohol in rats under operant self-administration conditions [102] Drowsiness, weakness, dizziness, tiredness, trouble sleeping, headache nausea, constipation, increased urination [102] Ondansetron (4 μg twice daily)…”

Section: Vareniclinementioning

confidence: 99%

Neurochemical Evidence of Preclinical and Clinical Reports on Target-Based Therapy in Alcohol Used Disorder

et al. 2020

View full text Add to dashboard Cite

Alcohol use disorder (AUD) is a chronic relapsing disorder, which enforces a person to compulsively seek alcohol, restricting control over alcohol intake leads to emergence of an undesired emotional state during abstinence. There are recent advances for better understanding of neurocircuitry involved in the pathophysiology of AUD. Alcohol interaction with neuronal membrane proteins results in changes in neuronal circuits. It is also linked with the potential medication and their clinical validation concerning their pharmacological targets for alcoholic abstinence. This review covers research work from the past few decades on the therapeutic advances on treatment of alcohol dependence; further detailing the fundamental neurochemical mechanisms after alcohol administration. It also covers interaction of alcohol with GABAergic, glutaminergic, dopaminergic, serotonergic and opioid systems. This review further elaborated the neurobiology of noradrenergic, cholinergic and cannabinoid systems and their interaction with AUD. Elaborative information of potential drug targets under current exploration for AUD treatment with their mechanisms are reported here along with clinical outcomes and the associated side effects.

show abstract

Baclofen: Therapeutic Use and Potential of the Prototypic GABAB Receptor Agonist

Cited by 12 publications

References 146 publications

GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia

GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia

Perioperative opioid-minimization approach as a useful protocol in the management of patients with Ehlers–Danlos syndrome-hypermobility type, craniocervical instability and severe chronic pain who are to undergo occipito-cervical fixation

Neurochemical Evidence of Preclinical and Clinical Reports on Target-Based Therapy in Alcohol Used Disorder

Contact Info

Product

Resources

About