Baclofen-induced encephalopathy in overdose – Modeling of the electroencephalographic effect/concentration relationships and contribution of tolerance in the rat

Chartier, Magali; Malissin, Isabelle; Tannous, Salma; Labat, Laurence; Risède, Patricia; Mégarbane, Bruno; Chevillard, L

doi:10.1016/j.pnpbp.2018.05.016

Cited by 9 publications

(6 citation statements)

References 50 publications

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“…Tolerance may lead to variability in the clinical features of intoxication and even decrease its severity. Although development of tolerance to baclofen attenuates baclofen-induced encephalopathy in rats ( 24 ), further investigations are warranted. Tolerance to baclofen may affect patient management by differentiating between acutely intoxicated patients with no previous treatment by baclofen and baclofen-treated patients (“acute-on-chronic poisoning”).…”

Section: Discussionmentioning

confidence: 99%

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How to Manage Self-Poisoning With Baclofen in Alcohol Use Disorder? Current Updates

et al. 2018

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Specialists in addiction medicine continue to debate whether baclofen is still indicated to treat alcohol use disorders in view of conflicting results as to its efficacy. This review summarizes current knowledge on self-poisoning with baclofen focusing of alcohol-use disorder in order to provide an overview of the reliable scientific knowledge on management of such an intoxication. Moreover, as alcohol-dependent patients experience many psychiatric co-morbidities, the risk in suicide attempt using baclofen seems real. Numerous studies have suggested that patients given daily-doses of baclofen higher than 80 mg/day are more likely to attempt suicides than others. Following an ingestion of a large amount of baclofen, central nervous system depression is usually observed. Seizures require the patient to be admitted in intensive care unit and should be treated like other toxicological seizures. Cardiac complications include prolonged QTc interval, degree heart block, premature atrial contractions, and supraventricular tachycardia, hypotension and bradycardia. In cases of intoxication, the elimination half-life of baclofen may last between 12 and 36 h post-overdose and renal failure is known to delay its clearance. Rarely measured in clinical practice, the toxic level of baclofen blood level ranges from 1.1 to 3.5 mg/l, and coma or fatal intoxication are observed from 6 to 9.6 mg/l. Baclofen withdrawal has been observed but making the diagnosis of withdrawal in case of suspected self-poisoning is difficult as baclofen intoxication and baclofen withdrawal share many clinical signs. Admission to hospital to manage of suicide attempt with baclofen is mandatory and should not be limited to baclofen alone. It needs to include other aspects of the overall care of patients with alcohol disorders (psychological and psychosocial interventions, management of comorbid mental conditions and physical complications).

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Section: Discussionmentioning

confidence: 99%

“…Marked electroencephalographic abnormalities combine slowing down of the background activity with paroxysmal activity. In severe overdose, burst-suppression has been observed ( 24 ), and electroencephalogram should be continuously recorded until the abnormal features disappear.…”

Section: Clinical Presentationmentioning

confidence: 99%

How to Manage Self-Poisoning With Baclofen in Alcohol Use Disorder? Current Updates

et al. 2018

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“…In a separate study, 12 shrews were randomly assigned to two groups and treated as follows: the Baclofen group (n = 6), lower abdominal surgery followed by single‐dose 5 mg/kg intraperitoneal injection of baclofen (a GABA B receptor agonist); and the Vehicle group (n = 6), surgery followed by intraperitoneal injection of normal saline alone. The doses of drugs were determined in preliminary experiments based on previous reports 13,14 . Baclofen or normal saline was administered at 3 min before the start of the emetic behavioral test.…”

Section: Methodsmentioning

confidence: 99%

“…The doses of drugs were determined in preliminary experiments based on previous reports. 13,14 Baclofen or normal saline was administered at 3 min before the start of the emetic behavioral test.…”

Section: Experimental Groupsmentioning

confidence: 99%

Antiemetic effects of baclofen in a shrew model of postoperative nausea and vomiting: Whole‐transcriptome analysis in the nucleus of the solitary tract

et al. 2022

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Aims The molecular genetic mechanisms underlying postoperative nausea and vomiting (PONV) in the brain have not been fully elucidated. This study aimed to determine the changes in whole transcriptome in the nucleus of the solitary tract (NTS) in an animal model of PONV, to screen a drug candidate and to elucidate the molecular genetic mechanisms of PONV development. Methods Twenty‐one female musk shrews were assigned into three groups: the Surgery group (shrew PONV model, n = 9), the Sham group (n = 6), and the Naïve group (n = 6). In behavioral studies, the main outcome was the number of emetic episodes. In genetic experiments, changes in the transcriptome in the NTS were measured. In a separate study, 12 shrews were used to verify the candidate mechanism underlying PONV. Results A median of six emetic episodes occurred in both the Sham and Surgery groups. Whole‐transcriptome analysis indicated the inhibition of the GABAB receptor‐mediated signaling pathway in the PONV model. Baclofen (GABAB receptor agonist) administration eliminated emetic behaviors in the shrew PONV model. Conclusions Our findings suggest that the GABAB receptor‐mediated signaling pathway is involved in emesis and that baclofen may be a novel therapeutic or prophylactic agent for PONV.

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“…121,133−135 Encephalopathy has also been reported in patients with varying degrees of renal dysfunctions. 136 ITB patients do risk pump malfunction, which can result in both drug overdose or underdose. 137,138 The incidence of overdose related to intrathecal baclofen use is less than 7% with some literature reporting 0%, and such cases are usually related to human error.…”

Section: ■ Adverse Eventsmentioning

confidence: 99%

Classics in Chemical Neuroscience: Baclofen

Kent

Park

Lindsley

2020

ACS Chem. Neurosci.

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Baclofen, β-(4-chlorophenyl)-γ-aminobutyric acid, holds a unique position in neuroscience, remaining the only U.S. Food and Drug Administration (FDA) approved GABAB agonist. While intended to be a more brain penetrant, i.e, ability to cross the blood-brain barrier (BBB), version of GABA (γ-aminobutyric acid) for the potential treatment of epilepsy, baclofen’s highly efficacious muscle relaxant properties led to its approval, as a racemate, for the treatment of spasticity. Interestingly, baclofen received FDA approval before its receptor, GABAB, was discovered and its exact mechanism of action was known. In recent times, baclofen has a myriad of off-label uses, with the treatment for alcohol abuse and drug addiction garnering a great deal of attention. This Review aims to capture the >60 year legacy of baclofen by walking through the history, pharmacology, synthesis, drug metabolism, routes of administration, and societal impact of this Classic in chemical neuroscience.

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Baclofen-induced encephalopathy in overdose – Modeling of the electroencephalographic effect/concentration relationships and contribution of tolerance in the rat

Cited by 9 publications

References 50 publications

How to Manage Self-Poisoning With Baclofen in Alcohol Use Disorder? Current Updates

How to Manage Self-Poisoning With Baclofen in Alcohol Use Disorder? Current Updates

Antiemetic effects of baclofen in a shrew model of postoperative nausea and vomiting: Whole‐transcriptome analysis in the nucleus of the solitary tract

Classics in Chemical Neuroscience: Baclofen

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