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ACS Chemical Neuroscience Jun 2020Baclofen, β-(4-chlorophenyl)-γ-aminobutyric acid, holds a unique position in neuroscience, remaining the only U.S. Food and Drug Administration (FDA) approved GABA... (Review)
Review
Baclofen, β-(4-chlorophenyl)-γ-aminobutyric acid, holds a unique position in neuroscience, remaining the only U.S. Food and Drug Administration (FDA) approved GABA 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, GABA, 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 in chemical neuroscience.
Topics: Alcoholism; Baclofen; Brain; Humans; Neurosciences; Receptors, GABA-B; gamma-Aminobutyric Acid
PubMed: 32436697
DOI: 10.1021/acschemneuro.0c00254 -
Neurosurgery Clinics of North America Apr 2019Intrathecal baclofen infusion is an accepted treatment for spasticity. Evidence also exists for the treatment of secondary generalized dystonia with intrathecal baclofen... (Review)
Review
Intrathecal baclofen infusion is an accepted treatment for spasticity. Evidence also exists for the treatment of secondary generalized dystonia with intrathecal baclofen infusion. Benefits include decreased tone, improved positioning, and decreased decubitus ulcers. Despite these benefits, there are significant complications that can occur with this therapy, including drug withdrawal, catheter infection, drug overdose, failure, and pump failure. In some cases, practitioners encourage a trial dose of intrathecal baclofen by injection or catheter infusion before pump implantation. To improve patient selection and outcomes many centers offering intrathecal baclofen therapy use a multidisciplinary team composed of physicians, surgeons, and physical therapists.
Topics: Baclofen; Humans; Injections, Spinal; Movement Disorders; Muscle Relaxants, Central; Treatment Outcome
PubMed: 30898271
DOI: 10.1016/j.nec.2018.12.002 -
BMJ Supportive & Palliative Care Sep 2023
Topics: Humans; Baclofen; Death
PubMed: 37595971
DOI: 10.1136/spcare-2022-003889 -
Therapie 2023Baclofen is widely used for spastic disorders and, most recently, for addictive disorders. The first signals of baclofen abuse occurred in the last decade. This study... (Review)
Review
BACKGROUND
Baclofen is widely used for spastic disorders and, most recently, for addictive disorders. The first signals of baclofen abuse occurred in the last decade. This study aims to assess the motives, diversion sources, and routes of administration associated with the non-medical use of baclofen and examine health problems related to the non-medical use of baclofen.
METHODS
Spontaneous reports of baclofen abuse reported to the addictovigilance centre of East France were analysed. A literature search was conducted using PubMed®, Web of Sciences®, and Google Scholar® databases. Both investigations were performed in February 2021 without a time limit.
RESULTS
Forty-six cases were analysed (33 from the literature review and 13 from the addictovigilance base). Baclofen's non-medical use mainly affected male subjects with addictive history, but issues of primary abuse in subjects without any substance abuse history were also observed. Euphoria search was the most common reason for misuse. The route of administration included oral, snorting, and sublingual use. Some cases involving illegal sources were also observed. Most patients misusing baclofen presented severe complications, mainly represented by neurological and respiratory disturbances. Physical and psychological dependence on baclofen was observed in three persons.
CONCLUSIONS
Although baclofen abuse remains relatively infrequent or (most likely) underestimated, this study helped confirm baclofen's intrinsic abuse potential and make visible the baclofen-abuse-related health visible harms. Careful consideration and benefit-risk analysis should be employed when prescribing baclofen, and emergency departments should be aware of baclofen dangers in abuse situations.
Topics: Humans; Male; Baclofen; Substance-Related Disorders; Behavior, Addictive; France
PubMed: 36922285
DOI: 10.1016/j.therap.2023.02.007 -
Biochemical and Biophysical Research... Apr 2022Between 30% and 50% of survivors of cardiac arrest (CA) suffer from cognitive deficits. However, no effective medical intervention is available to alleviate cognitive...
Between 30% and 50% of survivors of cardiac arrest (CA) suffer from cognitive deficits. However, no effective medical intervention is available to alleviate cognitive deficits. Baclofen is known to protect damaged neurons, but researchers have still not clearly whether baclofen alleviates CA-induced cognitive deficits. The present study aimed to investigate whether baclofen protects against post-CA cognitive deficits and to reveal the protective mechanism of baclofen. Rats underwent 10 min of asphyxia to establish CA models. Intriguingly, our results indicated that baclofen improved spatial memory 72 h after CA. Baclofen increased plasticity-related protein (PSD95, and GAP43) expression in the brain after CA. Baclofen reduced microglial number and the release of inflammatory factors (IL-1β and IL-18). Furthermore, baclofen significantly reduced the expression of pyroptosis-related molecules after CA. Notably, activation of NLRP3 abolished the anti-pyroptosis effect of baclofen and reduced the expression of synaptic plasticity-related proteins after CA. Taken together, this study first shows that baclofen attenuates cognitive deficits induced by brain injury after CA. The mechanism is at least partially attributed to baclofen regulating pyroptosis by inhibition of NLRP3 activation.
Topics: Animals; Baclofen; Brain Injuries; Cognition; Heart Arrest; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Rats; Rats, Sprague-Dawley
PubMed: 35272143
DOI: 10.1016/j.bbrc.2022.02.106 -
Archives of Neurology Nov 1977
Topics: Aminobutyrates; Baclofen; Drug Evaluation; Humans; Multiple Sclerosis; Muscle Spasticity
PubMed: 911241
DOI: 10.1001/archneur.1977.00500230092023 -
Clinical Neuropharmacology Aug 1992Dystonia refers to involuntary, prolonged muscle contractions leading to sustained, often twisting, postures. High dose anticholinergic therapy for childhood onset... (Review)
Review
Dystonia refers to involuntary, prolonged muscle contractions leading to sustained, often twisting, postures. High dose anticholinergic therapy for childhood onset dystonia, botulinum toxin injections for focal dystonia, and levodopa for diurnal dystonia provide symptomatic relief for some patients. Despite this, treatment of both idiopathic and secondary dystonia remains inadequate for many patients. Baclofen, a pre-synaptic acting GABA agonist, has been reported to benefit dystonia in a number of retrospective studies. Dramatic improvement in symptoms, especially in gait, was found in almost 30% of 31 children and adolescents with idiopathic dystonia in one retrospective study using doses ranging from 40 to 180 mg daily. The response to baclofen of adults with focal dystonia is less dramatic. One series of 60 adults with cranial dystonia found sustained benefit in 18%. Smaller series have not consistently found significant benefit in adults. Baclofen has been used to treat several secondary dystonias: tardive dystonia has occasionally been reported to improve and there are isolated reports of improvement in dystonia occurring in Parkinson's disease and in glutaric aciduria.
Topics: Baclofen; Dystonia; Humans
PubMed: 1516073
DOI: 10.1097/00002826-199208000-00002 -
Biomedical Chromatography : BMC Jan 2017Baclofen is a commonly used racemic drug and has a simple chemical structure in terms of the presence of only one stereogenic center. Since the desirable pharmacological... (Review)
Review
Baclofen is a commonly used racemic drug and has a simple chemical structure in terms of the presence of only one stereogenic center. Since the desirable pharmacological effect is in only one enantiomer, several possibilities exist for the other enantiomer for evaluation of the disposition of the racemic mixture of the drug. This calls for the development of enantioselective analytical methodology. This review summarizes and evaluates different methods of enantioseparation of (RS)-baclofen using both direct and indirect approaches, application of certain chiral reagents and chiral stationary phases (though very expensive). Methods of separation of diastereomers of (RS)-baclofen prepared with different chiral derivatizing reagents (under microwave irradiation at ease and in less time) on reversed-phase achiral columns or via a ligand exchange approach providing high-sensitivity detection by the relatively less expensive methods of TLC and HPLC are discussed. The methods may be helpful for determination of enantiomers in biological samples and in pharmaceutical formulations for control of enantiomeric purity and can be practiced both in analytical laboratories and industry for routine analysis and R&D activities.
Topics: Baclofen; Chromatography, High Pressure Liquid; GABA-B Receptor Agonists; Indicators and Reagents; Muscle Relaxants, Central; Stereoisomerism
PubMed: 27591736
DOI: 10.1002/bmc.3833 -
Bailliere's Clinical Neurology Apr 1993The intrathecal application of the GABA-B agonist baclofen has become more and more popular for severe spinal spasticity. Since it was first introduced in 1984 more than... (Review)
Review
The intrathecal application of the GABA-B agonist baclofen has become more and more popular for severe spinal spasticity. Since it was first introduced in 1984 more than 1000 patients worldwide have been treated by this method, using an implantable drug administration device. Clinical data from 48 patients are presented, as well as further experience from a multicentre trial conducted in Europe, in conjunction with a literature overview. The method is now generally accepted as a powerful treatment for spasticity due to spinal lesions of whatever aetiology; improvement in mobility and function as well as relief of spastic pain are the most obvious benefits for the patient. Bladder function is improved in terms of increased bladder volume and lowered residual volume. In patients with supraspinal lesions causing muscle hypertension, where several mechanisms usually contribute besides hyper-reflexia (spasticity), the response has been less pronounced, but intrathecal baclofen still seems to have clinical effects that are superior to those of any oral drug treatment. The initial technical and methodical problems have been solved and today the procedure is generally assessed as safe.
Topics: Baclofen; Humans; Injections, Spinal; Muscle Spasticity
PubMed: 8143075
DOI: No ID Found -
Psychosomatics 2014The gamma-aminobutyric acid type B receptor agonist baclofen is approved for spasticity and is used off-label for diverse types of addictive disorders, notably alcohol... (Review)
Review
BACKGROUND
The gamma-aminobutyric acid type B receptor agonist baclofen is approved for spasticity and is used off-label for diverse types of addictive disorders, notably alcohol dependence. Baclofen may induce numerous neuropsychiatric adverse drug reactions, including behavioral disinhibition. However, this precise adverse drug reaction has never been assessed using either a validated causality algorithm or a scale for manic symptoms.
METHODS
We report a case of a 49-year-old male patient who exhibited de novo mania during treatment with baclofen for alcohol dependence. Symptoms were evaluated using the Young Mania Rating Scale, and the causality of baclofen was determined using the Naranjo algorithm. This case was also compared with other cases of baclofen-induced mania through a systematic literature review.
RESULTS
Mr. X, taking 180 mg/d of baclofen, presented with mania and scored 24 of 44 on the Young Mania Rating Scale, and the imputability of baclofen was "probable" using the Naranjo algorithm (8 of 13). In addition, 4 other cases of baclofen-induced mania were reported in the literature; 3 cases had a bipolar I disorder history. Baclofen-induced manic symptoms occurred mostly during the dose-escalation phase.
CONCLUSION
Baclofen-induced manic symptoms may appear in patients with or without bipolar disorder. Particular attention is required during the dose-increase phase and in patients with a history of mood disorders.
Topics: Alcoholism; Baclofen; Bipolar Disorder; GABA-B Receptor Agonists; Humans; Male; Middle Aged
PubMed: 24751117
DOI: 10.1016/j.psym.2014.02.003