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Revision as of 09:56, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 464330982 of page Baclofen for the Chem/Drugbox validation project (updated: 'DrugBank').  Latest revision as of 05:13, 28 December 2024 edit Whywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers49,181 edits WP:REFPUNC 
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{{Short description|Medication for muscle movement disorders}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{Use dmy dates|date=October 2022}}
{{Drugbox
{{cs1 config|name-list-style=vanc|display-authors=6}}
| Verifiedfields = changed
{{Infobox drug
| verifiedrevid = 464186773
| Watchedfields = changed
| IUPAC_name = (''RS'')-4-amino-3-(4-chlorophenyl)butanoic acid
| verifiedrevid = 464365064
| image = Baclofen.svg | image = Baclofen.svg
| alt =
| imagename = 1 : 1 mixture (racemate)
| drug_name = Baclofen | image2 = Baclofen ball-and-stick model.png
| alt2 =
| chirality = ]


<!--Clinical data--> <!-- Clinical data -->
| tradename = Lioresal | tradename = Lioresal, others
| Drugs.com = {{drugs.com|monograph|baclofen}} | Drugs.com = {{drugs.com|monograph|baclofen}}
| licence_US = Baclofen | MedlinePlus = a682530
| DailyMedID = Baclofen
| pregnancy_US = C
| pregnancy_AU = B3
| routes_of_administration = ], ], ]
| ATC_prefix = M03
| ATC_suffix = BX01

| legal_AU = S4
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=] | date=6 June 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=8 June 2024 | archive-date=29 March 2024 | archive-url=https://web.archive.org/web/20240329200203/https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | url-status=live }}</ref>
| legal_NZ = Prescription only
| legal_UK = POM
| legal_US = Rx-only | legal_US = Rx-only
| legal_US_comment = <ref name="Gablofen FDA label" /><ref name="Lioresal FDA label">{{cite web | title=Lioresal (baclofen)- baclofen kit; Lioresal (baclofen)- baclofen injection | website=DailyMed | date=9 December 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6f3bdcc0-ffc8-4911-8c35-958c8103a2c5 | access-date=28 December 2024 | archive-date=3 August 2024 | archive-url=https://web.archive.org/web/20240803191151/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6f3bdcc0-ffc8-4911-8c35-958c8103a2c5 | url-status=live }}</ref><ref name="Ozobax FDA label">{{cite web | title=Ozobax- baclofen solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92153f69-bc9b-4bef-9a8e-751effde5c7e | access-date=7 November 2021 | archive-date=21 September 2022 | archive-url=https://web.archive.org/web/20220921190859/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92153f69-bc9b-4bef-9a8e-751effde5c7e | url-status=live }}</ref><ref name="Lyvispah FDA label">{{cite web | title=Lyvispah- baclofen granule | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a7d2dc58-e167-4ebc-ac1d-932f000fb412 | access-date=19 December 2021 | archive-date=21 September 2022 | archive-url=https://web.archive.org/web/20220921194439/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a7d2dc58-e167-4ebc-ac1d-932f000fb412 | url-status=live }}</ref><ref>{{cite web | title=Fleqsuvy- baclofen suspension | website=DailyMed | date=4 February 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9076d6ce-bbc2-4a9f-9cb9-2de1b675b9aa | access-date=16 March 2022 | archive-date=21 September 2022 | archive-url=https://web.archive.org/web/20220921225031/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9076d6ce-bbc2-4a9f-9cb9-2de1b675b9aa | url-status=live }}</ref>
| routes_of_administration = Oral, ]


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->
| bioavailability = well absorbed | bioavailability = Well-absorbed
| protein_bound = 30% | protein_bound = 30%
| metabolism = 85% excreted in urine/faeces unchanged. 15% metabolised by deamination | metabolism = 85% excreted in urine/faeces unchanged. 15% metabolised by deamination
| elimination_half-life = 1.5 to 4 hours | elimination_half-life = 1.5 to 4 hours
| excretion = renal (70-80%) | excretion = Kidney (70–80%)


<!--Identifiers--> <!-- Identifiers -->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 1134-47-0 | CAS_number = 1134-47-0
| ATC_prefix = M03
| ATC_suffix = BX01
| PubChem = 2284 | PubChem = 2284
| IUPHAR_ligand = 1084 | IUPHAR_ligand = 1084
| DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00181 | DrugBank = DB00181
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
Line 43: Line 53:
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 701 | ChEMBL = 701
| synonyms = β-(4-chlorophenyl)-γ-aminobutyric acid (β-(4-chlorophenyl)-GABA)


<!--Chemical data--> <!-- Chemical data -->
| IUPAC_name = (''RS'')-4-Amino-3-(4-chlorophenyl)butanoic acid
| C=10 | H=12 | Cl=1 | N=1 | O=2
| C=10 | H=12 | Cl=1 | N=1 | O=2
| molecular_weight = 213.661 g/mol
| smiles = Clc1ccc(cc1)C(CN)CC(=O)O | SMILES = NCC(CC(=O)O)c1ccc(Cl)cc1
| InChI = 1/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14)
| InChIKey = KPYSYYIEGFHWSV-UHFFFAOYAT
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14) | StdInChI = 1S/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14)
Line 55: Line 64:
| StdInChIKey = KPYSYYIEGFHWSV-UHFFFAOYSA-N | StdInChIKey = KPYSYYIEGFHWSV-UHFFFAOYSA-N
}} }}

<!-- Definition and medical uses -->
'''Baclofen''', sold under the brand name '''Lioresal''' among others, is a ] used to treat ], such as from a ] or ].<ref name="AHFS2019">{{cite web |title=Baclofen Monograph for Professionals |url=https://www.drugs.com/monograph/baclofen.html |access-date=3 March 2019 |website=Drugs.com |publisher=American Society of Health-System Pharmacists |archive-date=26 April 2019 |archive-url=https://web.archive.org/web/20190426153502/https://www.drugs.com/monograph/baclofen.html |url-status=live }}</ref><ref name="BNF76">{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=978-0-85711-338-2|pages=1092|edition=76}}</ref> It may also be used for ] and ] near the end of life<ref name="BNF76" />, and ] to treat ]<ref name=":0">{{cite journal | vauthors = Agabio R, Saulle R, Rösner S, Minozzi S | title = Baclofen for alcohol use disorder | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD012557 | date = January 2023 | pmid = 36637087 | pmc = 9837849 | doi = 10.1002/14651858.cd012557.pub3 }}</ref><ref name="baclofenvsclonidine">{{cite journal | vauthors = Ahmadi-Abhari SA, Akhondzadeh S, Assadi SM, Shabestari OL, Farzanehgan ZM, Kamlipour A | title = Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 26 | issue = 1 | pages = 67–71 | date = February 2001 | pmid = 11286609 | doi = 10.1111/j.1365-2710.2001.00325.x | s2cid = 28295723 }}</ref> or ] symptoms.<ref name="baclofenmaintenance">{{cite journal | vauthors = Assadi SM, Radgoodarzi R, Ahmadi-Abhari SA | title = Baclofen for maintenance treatment of opioid dependence: a randomized double-blind placebo-controlled clinical trial | journal = BMC Psychiatry | volume = 3 | pages = 16 | date = November 2003 | pmid = 14624703 | pmc = 293465 | doi = 10.1186/1471-244X-3-16 | doi-access = free }}</ref> It is taken ] or by ] (delivered into the spinal canal via an implantable pump device).<ref name="AHFS2019" /> It is sometimes used ]ly (applied topically to the skin) in combination with ] and ] prepared at a ].<ref name="compounding">{{cite web |url=https://www.uspharmacist.com/article/baclofen-2-gabapentin-6-and-clonidine-hydrochloride-01-in-pluronic-lecithin-organogel |title=Baclofen 2%, Gabapentin 6%, and Clonidine Hydrochloride 0.1% in Pluronic Lecithin Organogel |vauthors=Allen Jr LV |date=17 November 2010 |website=U.S. Pharmacist |publisher=Jobson Medical Information LLC |access-date=9 August 2023 |quote= |archive-date=10 August 2023 |archive-url=https://web.archive.org/web/20230810230423/https://www.uspharmacist.com/article/baclofen-2-gabapentin-6-and-clonidine-hydrochloride-01-in-pluronic-lecithin-organogel |url-status=live }}</ref> It is believed to work by decreasing levels of certain ].<ref name="AHFS2019" />

<!-- Side effects and mechanisms -->
Common side effects include sleepiness, weakness, and dizziness.<ref name=AHFS2019/> Serious side effects, such as ] and ], may occur if use of baclofen is stopped abruptly.<ref name="AHFS2019" /> Use during ] is of unclear safety, whilst use during ] is likely safe, and even more so if oral administration is avoided.<ref name="Preg2019">{{Cite web |title=Baclofen use while Breastfeeding |url=https://www.drugs.com/breastfeeding/baclofen.html |access-date=2024-12-28 |website=Drugs.com |archive-date=19 June 2024 |archive-url=https://web.archive.org/web/20240619074002/https://www.drugs.com/breastfeeding/baclofen.html |url-status=live }}</ref>

The adverse effects and safety profile associated with baclofen when it is combined with ] (for example ] or ]) range depending on the dose and the individual. The interaction may increase the sedative effects of all ingested sedatives and as such is not generally recommended.<ref>{{Cite web |date=2022-03-03 |title=Common questions about baclofen |url=https://www.nhs.uk/medicines/baclofen/common-questions-about-baclofen/ |access-date=2024-03-24 |website=nhs.uk |archive-date=24 March 2024 |archive-url=https://web.archive.org/web/20240324003119/https://www.nhs.uk/medicines/baclofen/common-questions-about-baclofen/ |url-status=live }}</ref> In high doses the interaction can cause ].<ref>{{Cite web |title=Seizures Following High-Dose Baclofen With Alcohol |url=http://www.medscape.com/viewarticle/769329 |access-date=2024-03-24 |website=Medscape |archive-date=28 June 2022 |archive-url=https://web.archive.org/web/20220628004830/https://www.medscape.com/viewarticle/769329 |url-status=live }}</ref>

<!-- History and culture -->
Baclofen was approved for medical use in the United States in 1977.<ref name=AHFS2019/> It is available as a ].<ref name="BNF76" /><ref>{{cite web | title=Competitive Generic Therapy Approvals | website=U.S. ] (FDA) | date=29 June 2023 | url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | access-date=29 June 2023 | archive-date=29 June 2023 | archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | url-status=live }}</ref> In 2022, it was the 104th most commonly prescribed medication in the United States, with more than 6{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Baclofen Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Baclofen | access-date = 30 August 2024 | archive-date = 12 April 2020 | archive-url = https://web.archive.org/web/20200412074434/https://clincalc.com/DrugStats/Drugs/Baclofen | url-status = live }}</ref>

==Medical uses==

Baclofen is primarily used for the treatment of ] disorders, especially in instances of spinal cord injury, and ].<ref name="AHFS">{{cite web | title = Baclofen | url = https://www.drugs.com/monograph/baclofen.html | work = The American Society of Health-System Pharmacists | access-date = 6 December 2011 | archive-date = 26 April 2019 | archive-url = https://web.archive.org/web/20190426153502/https://www.drugs.com/monograph/baclofen.html | url-status = live }}</ref> Use in people with ], ], or ] is not recommended.<ref name="AHFS" /> Intrathecal baclofen is used for severe spasticity of spinal cord origin, that is refractive to maximum doses of oral antispasmodic agents, or who experience intolerable side effects.<ref>{{cite book | vauthors = Ghanavatian S, Derian A | chapter = Baclofen | date = May 2022 | title = StatPearls | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 30252293 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK526037/ }}</ref><ref>{{cite book | vauthors = Siu G | date = 2014 | chapter = Pharmacotherapy | veditors = Maitin IB, Cruz E | title = CURRENT Diagnosis & Treatment: Physical Medicine & Rehabilitation. | publisher = McGraw Hill | url = https://accessmedicine.mhmedical.com/content.aspx?bookid=1180&sectionid=70377149 | isbn = 978-0-07-179329-2 | archive-date = 25 December 2022 | access-date = 25 December 2022 | archive-url = https://web.archive.org/web/20221225210133/https://accessmedicine.mhmedical.com/content.aspx?bookid=1180&sectionid=70377149 | url-status = live }}</ref>

Baclofen may be used off-label as a treatment for ] to reduce the risk of ], and to increase the number of days that a person can go without drinking ] (abstinence days).<ref name=":0" />

It is sometimes used for the treatment of ] symptoms, and may be superior for this purpose to the more-commonly used ].<ref name="baclofenvsclonidine" /><ref name="baclofenmaintenance" />

Baclofen is also used in the treatment of sleep-related painful erections.<ref>{{cite journal |vauthors=Vreugdenhil S, Weidenaar AC, de Jong IJ, van Driel MF |date=December 2017 |title=Sleep-Related Painful Erections-A Case Series of 24 Patients Regarding Diagnostics and Treatment Options |journal=Sexual Medicine |volume=5 |issue=4 |pages=e237–e243 |doi=10.1016/j.esxm.2017.09.001 |pmc=5693397 |pmid=29066083}}</ref>

==Adverse effects==
Adverse effects include drowsiness, dizziness, weakness, fatigue, headache, trouble sleeping, nausea and vomiting, poor concentration and recall (resembling dementia), urinary retention, or constipation.<ref name="Gablofen FDA label" />

===Withdrawal syndrome===
Discontinuation of baclofen can be associated with a withdrawal syndrome which resembles ] and ]. ] are more likely if baclofen is administered ] or for long periods of time (more than a couple of months) and can occur from low or high doses.<ref name="big_papa" /> The severity of baclofen withdrawal depends on the rate at which it is discontinued. Thus to minimise withdrawal symptoms, the dose should be tapered down slowly when discontinuing baclofen therapy. Abrupt withdrawal is more likely to result in severe withdrawal symptoms. Acute withdrawal symptoms can be eased or completely reversed by re-initiating therapy with baclofen.<ref name="dawbw">{{cite journal | vauthors = Leo RJ, Baer D | title = Delirium associated with baclofen withdrawal: a review of common presentations and management strategies | journal = Psychosomatics | volume = 46 | issue = 6 | pages = 503–507 | date = Nov–Dec 2005 | pmid = 16288128 | doi = 10.1176/appi.psy.46.6.503 | doi-access = free }}</ref>

Withdrawal symptoms may include ], ], ], ], ], ], ], ], fluctuation of consciousness, ], ], ], inattention, memory impairments, perceptual disturbances, ], ], ], ], ] (higher than normal temperature without infection), ], ], ], mood disturbances, ], and behavioral disturbances, ], ], ]s, ], ] (fever), extreme ] resembling ] and ] ].<ref name="dawbw" /><ref name="big_papa">{{cite journal | vauthors = Grenier B, Mesli A, Cales J, Castel JP, Maurette P | title = | journal = Annales Françaises d'Anesthésie et de Réanimation | volume = 15 | issue = 5 | pages = 659–662 | year = 1996 | pmid = 9033759 | doi = 10.1016/0750-7658(96)82130-7 }}</ref>

===Abuse===
]"]]

Baclofen, at standard dosing, does not appear to possess ] properties, and has not been associated with any degree of ].<ref name=Review10/><ref name="AgabioPreti2013">{{cite journal | vauthors = Agabio R, Preti A, Gessa GL | title = Efficacy and tolerability of baclofen in substance use disorders: a systematic review | journal = European Addiction Research | volume = 19 | issue = 6 | pages = 325–345 | year = 2013 | pmid = 23775042 | doi = 10.1159/000347055 | s2cid = 1315087 | doi-access =free }}</ref> Euphoria is however listed as a common to very common side-effect of baclofen in the ].<ref>{{Cite web|url=https://www.nice.org.uk/bnf-uk-only|title=BNF is only available in the UK|website=NICE|access-date=16 April 2019|archive-date=9 December 2020|archive-url=https://web.archive.org/web/20201209161059/https://www.nice.org.uk/bnf-uk-only|url-status=live}}</ref> There are very few cases of ] of baclofen for reasons other than ].<ref name=Review10/> In contrast to baclofen, another GABA<sub>B</sub> receptor agonist, ] (GHB), has been associated with euphoria, abuse, and addiction.<ref name="van NieuwenhuijzenMcGregor2009">{{cite journal | vauthors = van Nieuwenhuijzen PS, McGregor IS, Hunt GE | title = The distribution of gamma-hydroxybutyrate-induced Fos expression in rat brain: comparison with baclofen | journal = Neuroscience | volume = 158 | issue = 2 | pages = 441–455 | date = January 2009 | pmid = 18996447 | doi = 10.1016/j.neuroscience.2008.10.011 | s2cid = 22701676 }}</ref> These effects are likely mediated not by activation of the GABA<sub>B</sub> receptor, but rather by activation of the ].<ref name="van NieuwenhuijzenMcGregor2009" /> Baclofen possesses both ] and ] properties.<ref name="AgabioPreti2013" />

==Overdose==
Reports of ] indicate that baclofen may cause symptoms including ], ], ], ], ]s, dizziness<ref name="Gablofen FDA label">{{cite web | title=Gablofen- baclofen injection injection, solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00d3e846-dd92-448d-9ab8-6a07be823cc1 | access-date=7 November 2021 | archive-date=12 December 2022 | archive-url=https://web.archive.org/web/20221212094154/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00d3e846-dd92-448d-9ab8-6a07be823cc1 | url-status=live }}</ref>, headaches<ref name="Gablofen FDA label" />, ], ], ], cardiac conduction abnormalities, ], ] and ] sometimes mimicking ].<ref>{{cite journal | vauthors = Murphy L, Wolfer H, Hendrickson RG | title = Toxicologic Confounders of Brain Death Determination: A Narrative Review | journal = Neurocritical Care | volume = 34 | issue = 3 | pages = 1072–1089 | date = June 2021 | pmid = 33000377 | pmc = 7526708 | doi = 10.1007/s12028-020-01114-y }}</ref> Overdose may require ] and length of ] required may correlate with serum baclofen levels shortly after ingestion. Symptoms may persist even after the point at which serum baclofen levels are undetectable.<ref name="Perry1998">{{cite journal | vauthors = Perry HE, Wright RO, Shannon MW, Woolf AD | title = Baclofen overdose: drug experimentation in a group of adolescents | journal = Pediatrics | volume = 101 | issue = 6 | pages = 1045–1048 | date = June 1998 | pmid = 9606233 | doi = 10.1542/peds.101.6.1045 }}</ref>

==Pharmacology==
Chemically, baclofen is a derivative of the ] ] (GABA). It is believed to work by ], specifically the ].<ref name="TGA">{{cite web|title=Product Information Clofen|website=TGA eBusiness Services|publisher=Alphapharm Pty Limited|date=7 June 2017|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04975-3|access-date=15 August 2017|location=Millers Point, Australia|archive-date=15 August 2017|archive-url=https://web.archive.org/web/20170815185427/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04975-3|url-status=live}}</ref>

===Pharmacodynamics===
Baclofen produces its effects by selectively activating the ]. Baclofen is postulated to block mono-and-polysynaptic reflexes by acting as an inhibitory ligand, inhibiting the release of excitatory neurotransmitters. Baclofen does not have significant affinity for the ], and has no known abuse potential.<ref name="Carter-2009">{{cite journal | vauthors = Carter LP, Koek W, France CP | title = Behavioral analyses of GHB: receptor mechanisms | journal = Pharmacology & Therapeutics | volume = 121 | issue = 1 | pages = 100–114 | date = January 2009 | pmid = 19010351 | pmc = 2631377 | doi = 10.1016/j.pharmthera.2008.10.003 }}</ref> Agonism of GABA<sub>B</sub> receptors is thought to be responsible for baclofen's range of therapeutic properties, as ] knockout mice are unresponsive to the neurobiological effects of baclofen.<ref>{{cite journal | vauthors = Durant CF, Paterson LM, Turton S, Wilson SJ, Myers JF, Muthukumaraswamy S, Venkataraman A, Mick I, Paterson S, Jones T, Nahar LK, Cordero RE, Nutt DJ, Lingford-Hughes A | title = Using Baclofen to Explore GABA-B Receptor Function in Alcohol Dependence: Insights From Pharmacokinetic and Pharmacodynamic Measures | language = English | journal = Frontiers in Psychiatry | volume = 9 | pages = 664 | date = 2018-12-14 | pmid = 30618857 | doi = 10.3389/fpsyt.2018.00664 | doi-access = free | pmc = 6302106 }}</ref>

Similarly to ] (β-phenyl-GABA), as well as ] (β-isobutyl-GABA), which are close analogues of baclofen, baclofen (β-(4-chlorophenyl)-GABA) has been found to block ]-containing ]s (VGCCs).<ref name="pmid26234470">{{cite journal | vauthors = Zvejniece L, Vavers E, Svalbe B, Veinberg G, Rizhanova K, Liepins V, Kalvinsh I, Dambrova M | title = R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects | journal = Pharmacology, Biochemistry, and Behavior | volume = 137 | pages = 23–29 | date = October 2015 | pmid = 26234470 | doi = 10.1016/j.pbb.2015.07.014 | s2cid = 42606053 }}</ref> However, it is weaker relative to phenibut in this action (K<sub>i</sub>&nbsp;= 23 and 39&nbsp;μM for ''R''- and ''S''-phenibut and 156&nbsp;μM for baclofen).<ref name="pmid26234470" /> Moreover, baclofen is in the range of 100-fold more potent by weight as an agonist of the GABA<sub>B</sub> receptor in comparison to phenibut, and in accordance, is used at far lower relative dosages. As such, the actions of baclofen on α<sub>2</sub>δ subunit-containing VGCCs are likely not clinically relevant.<ref name="pmid26234470" />

For drug-reward and addiction, baclofen's mechanism of action is thought to be through its effect on the mesolimbic dopamine pathway, specifically leading to a decrease in dopamine release associated with alcohol.<ref name=":0" /> GABA<sub>B</sub> receptor activation (GABA<sub>B</sub> receptor agonist activity) may decrease or inhibit alcohol's ability to activate or fire dopaminergic neurons following exposure to alcohol. Baclofen's mechanism of action when used to treat alcohol use disorder is not thought to be mediated through its muscle-relaxing or sedative properties, however there is evidence to suggest that the GABA<sub>B</sub> receptor-activation in the limbus may also reduce feelings of anxiety in people with alcohol use disorder.<ref name=":0" />

===Pharmacokinetics===
The drug is rapidly absorbed after oral administration and is widely distributed throughout the body. Biotransformation is low: the drug is predominantly excreted unchanged by the kidneys.<ref>{{cite journal | vauthors = Wuis EW, Dirks MJ, Termond EF, Vree TB, Van der Kleijn E | title = Plasma and urinary excretion kinetics of oral baclofen in healthy subjects | journal = European Journal of Clinical Pharmacology | volume = 37 | issue = 2 | pages = 181–184 | year = 1989 | pmid = 2792173 | doi = 10.1007/BF00558228 | s2cid = 23828250 }}</ref> The ] of baclofen is roughly 2–4 hours; it therefore needs to be administered frequently throughout the day to control spasticity appropriately.

==Chemistry==
Baclofen is a white (or off-white) mostly odorless ] powder, with a ] of 213.66 g/mol. It is slightly ] in water, very slightly soluble in ], and insoluble in ].

==History==
Historically, baclofen was designed as a drug for treating epilepsy. It was first synthesized at ], by the Swiss chemist Heinrich Keberle, in 1962.<ref>{{Cite book | vauthors= Froestl W | veditors= Blackburn TP | title= GABAb Receptor Pharmacology – A Tribute to Norman Bowery | chapter= Chemistry and Pharmacology of GABAb Receptor Ligands | series= Advances in Pharmacology | volume= 58 | pages= 19–62 | year= 2010 | isbn= 978-0-12-378647-0 | doi= 10.1016/S1054-3589(10)58002-5 | pmid= 20655477 | chapter-url= https://books.google.com/books?id=_iMDQOA2UIsC&pg=PA19 | archive-date= 29 September 2024 | access-date= 5 January 2016 | archive-url= https://web.archive.org/web/20240929051346/https://books.google.com/books?id=_iMDQOA2UIsC&pg=PA19#v=onepage&q&f=false | url-status= live }}</ref><ref>{{cite journal | vauthors = Yogeeswari P, Ragavendran JV, Sriram D | title = An update on GABA analogs for CNS drug discovery | journal = Recent Patents on CNS Drug Discovery | volume = 1 | issue = 1 | pages = 113–118 | date = January 2006 | pmid = 18221197 | doi = 10.2174/157488906775245291 | url = http://www.bentham.org/rpcn/samples/rpcn1-1/Yogeeswari.pdf | url-status = dead | archive-url = https://web.archive.org/web/20100616045343/http://bentham.org/rpcn/samples/rpcn1-1/Yogeeswari.pdf | archive-date = 16 June 2010 }}</ref> Its effect on epilepsy was ineffective, but it was found that in certain people, spasticity decreased. In 1971, it was introduced as a treatment for certain form of spasticity. It was approved by the ] (FDA) in 1977.<ref name =Romito>{{cite journal | vauthors = Romito JW, Turner ER, Rosener JA, Coldiron L, Udipi A, Nohrn L, Tausiani J, Romito BT | title = Baclofen therapeutics, toxicity, and withdrawal: A narrative review | journal = SAGE Open Medicine | volume = 9 | issue = | pages = 20503121211022197 | date = 2021 | pmid = 34158937 | pmc = 8182184 | doi = 10.1177/20503121211022197 }}</ref>

] baclofen was first introduced in 1984 to treat severe spinal spasticity. This administration route aimed to avoid supraspinal side effects.<ref name="pmid8143075">{{cite journal | vauthors = Ochs GA | title = Intrathecal baclofen | journal = Baillière's Clinical Neurology | volume = 2 | issue = 1 | pages = 73–86 | date = April 1993 | pmid = 8143075 | doi = | url = }}</ref><ref name="pmid12746702">{{cite journal | vauthors = Sallerin B, Lazorthes Y | title = | language = French | journal = Neuro-Chirurgie | volume = 49 | issue = 2-3 Pt 2 | pages = 271–5 | date = May 2003 | pmid = 12746702 | doi = | url = }}</ref>

In his 2008 book, '']'' (translated literally as ''The Last Glass'' or ''The End of my Addiction''), French-American cardiologist ] described how he treated his alcoholism with baclofen. Inspired by this book, an anonymous donor gave $750,000 to the ] in the Netherlands to initiate a clinical trial of high-dose baclofen, which Ameisen had called for since 2004.<ref name=SCIAMEISEN>{{cite journal | vauthors = Enserink M | title = Addiction research. Anonymous alcoholic bankrolls trial of controversial therapy | journal = Science | volume = 332 | issue = 6030 | pages = 653 | date = May 2011 | pmid = 21551041 | doi = 10.1126/science.332.6030.653 | bibcode = 2011Sci...332..653E }}</ref> The trial conclude, "In summary, the current study did not find evidence of a positive effect of either low or high doses of baclofen in AD patients. However, we cannot exclude the possibility that baclofen is an effective medication for the treatment of severe, heavy drinking AD patients not responding to or not accepting routine psychosocial interventions."<ref>{{cite journal | vauthors = Beraha EM, Salemink E, Goudriaan AE, Bakker A, de Jong D, Smits N, Zwart JW, Geest DV, Bodewits P, Schiphof T, Defourny H, van Tricht M, van den Brink W, Wiers RW | title = Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial | journal = European Neuropsychopharmacology | volume = 26 | issue = 12 | pages = 1950–1959 | date = December 2016 | pmid = 27842939 | doi = 10.1016/j.euroneuro.2016.10.006 | s2cid = 26005283 | hdl = 11245.1/cbb8e3d3-f5a2-4c1a-9e6d-f78c44e3cedb | url = https://dare.uva.nl/personal/pure/en/publications/efficacy-and-safety-of-highdose-baclofen-for-the-treatment-of-alcohol-dependence(cbb8e3d3-f5a2-4c1a-9e6d-f78c44e3cedb).html | hdl-access = free }}</ref>

==Society and culture==

===Routes of administration===
]

Baclofen can be administered, orally, intrathecally (directly into the cerebral spinal fluid) using a pump implanted under the skin, or transdermally as part of a pain-relieving and muscle-relaxing topical cream mix (also containing gabapentin and clonidine) prepared at a compounding pharmacy.<ref name=compounding/><ref name=Krach2009/>

]s offer much lower doses of baclofen because they are designed to deliver the medication directly to the spinal fluid rather than going through the digestive and blood system first. A drug concentration in the cerebrospinal fluid more than 10 times greater than when given orally is achieved with this route. At the same time the blood concentration levels are almost undetectable, thus minimizing side effects.<ref name=Krach2009>{{cite journal | vauthors = Krach LE | title = Intrathecal baclofen use in adults with cerebral palsy | journal = Developmental Medicine and Child Neurology | volume = 51 | issue = Suppl 4 | pages = 106–12 | date = October 2009 | pmid = 19740217 | doi = 10.1111/j.1469-8749.2009.03422.x | s2cid = 20049367 | url = | doi-access = free }}</ref>

Besides those with spasticity, intrathecal administration is also used in patients with ]<ref name=Krach2009/> or ] who have severe painful spasms which are not controllable by oral baclofen.{{citation needed|date=December 2022}} With pump administration, a test dose is first injected into the spinal fluid to assess the effect, and if successful in relieving spasticity, a chronic intrathecal catheter is inserted from the spine through the abdomen and attached to the pump which is implanted under the abdomen's skin, usually by the ribcage.{{citation needed|date=December 2022}} The pump is computer-controlled for automatic dosage and its reservoir can be replenished by ] injection.{{citation needed|date=December 2022}} The pump also has to be replaced every five to seven years or so.<ref>{{cite web |title=Intrathecal Baclofen Therapy for Spasticity |url=http://sci.washington.edu/info/forums/reports/intrathecal_baclofen.asp |website=Northwest Regional Spinal Cord Injury System |publisher=University of Washington |access-date=21 March 2024}}</ref>

===Other names===
Other names include: Fleqsuvy, Gablofen, Kemstro, Lioresal, Lyvispah, Ozobax.<ref>{{Cite web |title=Baclofen |url=https://go.drugbank.com/drugs/DB00181 |access-date=2024-12-28 |website=go.drugbank.com |archive-date=1 September 2024 |archive-url=https://web.archive.org/web/20240901150353/https://go.drugbank.com/drugs/DB00181 |url-status=live }}</ref>

==Research==
Baclofen is being studied for the treatment of alcoholism.<ref name=Review10>{{cite journal | vauthors = Leggio L, Garbutt JC, Addolorato G | title = Effectiveness and safety of baclofen in the treatment of alcohol dependent patients | journal = CNS & Neurological Disorders Drug Targets | volume = 9 | issue = 1 | pages = 33–44 | date = March 2010 | pmid = 20201813 | doi = 10.2174/187152710790966614 }}</ref> Evidence as of 2019 is not conclusive enough to recommend its use for this purpose.<ref name=Review10/><ref>{{cite journal | vauthors = Liu J, Wang LN | title = Baclofen for alcohol withdrawal | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 11 | date = November 2019 | pmid = 31689723 | pmc = 6831488 | doi = 10.1002/14651858.CD008502.pub6 }}</ref> In 2014, the French drug agency ] issued a three-year temporary recommendation allowing the use of baclofen in alcoholism.<ref>{{cite web | url = http://ansm.sante.fr/S-informer/Points-d-information-Points-d-information/Une-recommandation-temporaire-d-utilisation-RTU-est-accordee-pour-le-baclofene-Point-d-information | title = Une recommandation temporaire d'utilisation (RTU) est accordée pour le baclofène – Point d'information | trans-title = A temporary recommendation for use (RTU) is granted for baclofen – Information point | work = L'Agence nationale de sécurité du médicament et des produits de santé (ANSM) | trans-work = The National Agency for the Safety of Medicines and Health Products | date = 14 March 2014 | access-date = 2 March 2016 | archive-date = 7 March 2016 | archive-url = https://web.archive.org/web/20160307071205/http://ansm.sante.fr/S-informer/Points-d-information-Points-d-information/Une-recommandation-temporaire-d-utilisation-RTU-est-accordee-pour-le-baclofene-Point-d-information | url-status = live }}</ref> In 2018, baclofen received a Marketing Authorization for use in alcoholism treatment from the agency if all other treatments are not effective.<ref>{{cite web |title=Autorisation du baclofène: des conditions d'utilisation trop restrictives ? - A la une | trans-title = Authorization of baclofen: too restrictive conditions of use? - Featured |url=https://destinationsante.com/autorisation-du-baclofene-des-conditions-dutilisation-trop-restrictives.html | archive-url = https://web.archive.org/web/20181025143149/https://destinationsante.com/autorisation-du-baclofene-des-conditions-dutilisation-trop-restrictives.html | archive-date = 25 October 2018 | work = L'Agence nationale de sécurité du médicament et des produits de santé (ANSM) | trans-work = The National Agency for the Safety of Medicines and Health Products |language=fr-FR |date=25 October 2018}}</ref>

It is being studied along with ] and ] for ] (CMT), a hereditary disease that causes ].<ref>{{cite journal | vauthors = Attarian S, Vallat JM, Magy L, Funalot B, Gonnaud PM, Lacour A, Péréon Y, Dubourg O, Pouget J, Micallef J, Franques J, Lefebvre MN, Ghorab K, Al-Moussawi M, Tiffreau V, Preudhomme M, Magot A, Leclair-Visonneau L, Stojkovic T, Bossi L, Lehert P, Gilbert W, Bertrand V, Mandel J, Milet A, Hajj R, Boudiaf L, Scart-Grès C, Nabirotchkin S, Guedj M, Chumakov I, Cohen D | title = An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A | journal = Orphanet Journal of Rare Diseases | volume = 9 | issue = 1 | pages = 199 | date = December 2014 | pmid = 25519680 | pmc = 4311411 | doi = 10.1186/s13023-014-0199-0 | doi-access = free }}</ref> It is also being studied for cocaine addiction.<ref>{{cite journal | vauthors = Kampman KM | title = New medications for the treatment of cocaine dependence | journal = Psychiatry | volume = 2 | issue = 12 | pages = 44–48 | date = December 2005 | pmid = 21120115 | pmc = 2994240 }}</ref> Baclofen and other muscle relaxants are being studied for potential use for persistent hiccups.<ref>{{cite web | url = https://www.medscape.com/viewarticle/844420 | title = What Is the Latest on Treatment for Hiccups? | publisher = Medscape | access-date = 29 July 2018 | archive-date = 16 May 2017 | archive-url = https://web.archive.org/web/20170516093749/http://www.medscape.com/viewarticle/844420 | url-status = live }}</ref><ref>{{cite journal | vauthors = Walker P, Watanabe S, Bruera E | title = Baclofen, a treatment for chronic hiccup | journal = Journal of Pain and Symptom Management | volume = 16 | issue = 2 | pages = 125–132 | date = August 1998 | pmid = 9737104 | doi = 10.1016/S0885-3924(98)00039-6 | doi-access = free }}</ref>

From 2014 to 2017 baclofen misuse, toxicity and use in suicide attempts among adults in the US increased.<ref>{{cite journal | vauthors = Reynolds K, Kaufman R, Korenoski A, Fennimore L, Shulman J, Lynch M | title = Trends in gabapentin and baclofen exposures reported to U.S. poison centers | journal = Clinical Toxicology | volume = 58 | issue = 7 | pages = 763–772 | date = July 2020 | pmid = 31786961 | doi = 10.1080/15563650.2019.1687902 | s2cid = 208537638 | doi-access = free }}</ref>

== References ==
{{Reflist}}

{{Muscle relaxants}}
{{Drugs used in addictive disorders}}
{{GABA receptor modulators}}
{{Ion channel modulators}}
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