Acamprosate 3560079 223647782 2008-07-05T02:00:34Z AkhtaBot 6756213 robot Adding: [[ar:أكامبروسيت]] {{drugbox | IUPAC_name = 3-Acetamidopropane-1-sulfonic acid | image = Acamprosate structure.png | CAS_number = 77337-76-9 | ATC_prefix = N07 | ATC_suffix = BB03 | ATC_supplemental = | PubChem = 71158 | DrugBank = APRD00661 | C=10 | H=20 | N=2 | O=8 | S=2 | molecular_weight = 181.211 g/mol | bioavailability = 11%<ref name="fda"/> | protein_bound = Negligible<ref name="fda"/> | metabolism = Nil<ref name="fda"/> | elimination_half-life = 20 to 33 [[hour]]s<ref name="fda"/> | pregnancy_category = C<ref name="deluca">{{cite web| title=Acamprosate (Campral): Medication for Alcohol Abuse and Alcoholism Treatment | author= DeLuca, Alexander | publisher = doctordeluca.com | url = http://www.doctordeluca.com/Documents/AcamprosateSummary.htm | accessdate = 2007-01-08}}</ref> <small>([[United States|US]])</small> B2 <small>([[Australia|AU]])</small> | legal_US = Rx-only | legal_UK = POM | routes_of_administration = Oral (333mg tablets of acamprosate calcium)<ref name="fda"/> | excretion = [[Renal]]<ref name="fda"/> }} '''Acamprosate''', also known by the brand name '''Campral''', is a drug used for treating [[alcohol dependence]]. Acamprosate is thought to stabilize the chemical balance in the [[brain]] that would otherwise be disrupted by alcoholism, possibly by blocking glutaminergic ''N''-methyl-<small>D</small>-aspartate [[Receptor (biochemistry)|receptor]]s, while [[gamma-aminobutyric acid]] (GABA) type A receptors are activated.<ref name="americanfamilyphysician">Williams SH. (2005). "[http://www.aafp.org/afp/20051101/1775.html Medications for treating alcohol dependence]". ''American Family Physician'' '''72''' (9): 1775-1780. PMID 16300039</ref> Reports indicate that acamprosate only works with a combination of attending [[support group]]s and [[abstinence]] from [[alcohol]].<ref name=Mason2001>Mason BJ. "Treatment of alcohol-dependent outpatients with acamprosate: a clinical review". ''J Clin Psychiatry'' 2001;'''62'''(suppl 20):42-8. PMID 11584875</ref> Certain serious side effects include [[allergic reaction]]s, [[Cardiac arrhythmia|irregular heartbeat]]s, and low or high [[blood pressure]], while less serious side effects include [[headache]]s, [[insomnia]], and [[impotence]].<ref>{{cite web | title= Acamprosate | publisher = drugs.com | date = [[2005-03-25]] | accessdate = 2007-01-08 | url=http://www.drugs.com/mtm/acamprosate.html}}</ref> Acamprosate should not be taken by people with [[kidney]] problems or allergies to the drug.<ref>{{cite web | url = http://www.webmd.com/drugs/drug-91488-Acamprosate+Oral.aspx?drugid=91488&drugname=Acamprosate+Oral&pagenumber=5 | title = Acamprosate Oral - Who should not take this medication? | publisher = WebMD.com | accessdate = 2007-01-08 }}</ref> Campral is manufactured and marketed in the United States by Forest Laboratories, while [[Merck KGaA]] markets it outside the US. It is sold as 333 [[milligram|mg]] [[white]] and [[odor]]less [[tablet]]s of acamprosate calcium, which is the equivalent of 300mg of acamprosate.<ref name="fda">{{cite web | title = Campral Description | accessdate=2006-04-02 | url = http://www.fda.gov/cder/foi/label/2004/21431lbl.pdf | format = PDF}}</ref> ==Approval== While the [[Food and Drug Administration]] (FDA) in the [[United States]] approved this drug in July 2004, it has been legal in [[Europe]] since 1989. After it approved the drug, the FDA released this statement: : "While its mechanism of action is not fully understood, Campral is thought to act on the [[brain]] pathways related to alcohol abuse. Campral was demonstrated to be safe and effective by multiple [[placebo]]-controlled [[clinical trial|clinical studies]] involving alcohol-dependent patients who had already been withdrawn from alcohol, (i.e., [[Drug rehabilitation|detoxified]]). Campral proved superior to placebo in maintaining [[abstinence]] (keeping patients off alcohol consumption), as indicated by a greater percentage of acamprosate-treated subjects being assessed as continuously abstinent throughout treatment. Campral is not [[addiction|addicting]] and was generally well-tolerated in clinical trials. The most common [[adverse drug reaction|adverse events]] reported for patients taking Campral included [[headache]], [[diarrhea]], [[flatulence]], and [[nausea]]."<ref>{{cite web| title = FDA Approves New Drug for Treatment of Alcoholism | date = [[2004-07-29]] | accessdate = 2007-01-08 | publisher = FDA | url = http://www.fda.gov/bbs/topics/answers/2004/ANS01302.html}}</ref> ==Study results== The [[Scripps Research Institute]] conducted a [[double blind]] study comparing the effectiveness between using acamprosate and [[placebo]]s in combination with [[psychotherapy]]. The primary end-point evaluated was percentage of alcohol-free days. The researchers concluded that acamprosate is "safe and effective".<ref name=Mason2006>{{cite journal | last = Mason | first = BJ | coauthors = Goodman AM, Chabac S, Lehert P | title = Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: The role of patient motivation | journal = J Psychiatr Res | volume = 40 | issue = 5 | pages = 383&ndash;393 | year = 2006 | pmid = 16546214 | doi = 10.1016/j.jpsychires.2006.02.002}}</ref> Another study was conducted by [[Princess Alexandra Hospital]] in [[Brisbane]] comparing the use of acamprosate, [[naltrexone]], and both drugs at once in a twelve-week study.<ref> {{cite journal | last = Feeney | first = GF | coauthors = Connor JP, Young RM, Tucker J, McPherson A | title = Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: A single centre's experience with pharmacotherapy | journal = Alcohol Alcohol | volume = 41 | issue = 3 | pages = 321&ndash;327 | year = 2006 | pmid = 16467406 }} </ref> Three groups of 59 patients were tested with [[cognitive behavioral therapy]]; each group with each form of treatment outlined for this study. The results are outlined below. {| class="wikitable" |- <span style="float: center"> ! ! Percentage attending program ! Abstinence rates ! Average number of days abstinence<sup>1</sup> ! Days until first breach of abstinence<sup>1</sup> </span> |- | Acamprosate group | 66.1% | 50.8% | 45.07 days | 26.79 days |- | Naltrexone group | 79.7% | 66.1% | 49.95 days | 26.7 days |- | Drug combination group | 83.1% | 67.8% | 53.58 days | 37.32 days |} : <sup>1</sup> ''This statistic applies to patients who could not remain abstinent throughout the entire 84-day period.'' This study concluded that a combination of medications was generally more popular and yielded better results than using either drug alone. ==Physiological action== Alcohol inhibits activity of [[biochemical receptor]]s called [[N-methyl-D-aspartate receptor]]s, or NMDARs, so that chronic alcohol consumption leads to the overproduction of these receptors. Thus, sudden alcohol abstinence causes these excessive numbers of NMDARs to be more active than normal and to produce the symptoms of [[delirium tremens]] and [[excitotoxicity|excitotoxic]] neuronal death.<ref>Tsai G, Coyle JT. 1998. The role of glutamatergic neurotransmission in the pathophysiology of alcoholism. Annual Review of Medicine, '''49''': 173-184. PMID 9509257. Retrieved on [[March 4]], [[2007]].</ref> [[Withdrawal]] from alcohol induces a surge in release of excitatory [[neurotransmitter]]s like [[Glutamic acid|glutamate]], which activates NMDARs.<ref>Tsai GE, Ragan P, Chang R, Chen S, Linnoila VM, Coyle JT. (1998). [http://ajp.psychiatryonline.org/cgi/content/full/155/6/726 "Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal."] ''American Journal of Psychiatry'', '''155''' (6): 726-732. PMID 9619143. Retrieved on [[March 4]], [[2007]].</ref> Acamprosate reduces this glutamate surge.<ref name="De Witte 2005">De Witte P, Littleton J, Parot P, Koob G. (2005). "Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action." ''CNS Drugs'' '''19''' (6): 517-537. PMID 15963001. Retrieved on [[March 4]], [[2007]].</ref> The drug also protects cultured cells in excitotoxicity induced by ethanol withdrawal.<ref>Mayer S, Harris BR, Gibson DA, Blanchard JA, Prendergast MA, Holley RC, Littleton J. (2002). "Acamprosate, MK-801, and ifenprodil inhibit neurotoxicity and calcium entry induced by ethanol withdrawal in organotypic slice cultures from neonatal rat hippocampus." ''Alcoholism, Clinical and Experimental Research'', '''26''' (10): 1468-1478. PMID 12394279. Retrieved on [[March 4]], [[2007]].</ref> and by glutamate exposure combined with ethanol withdrawal.<ref>al Qatari M, Khan S, Harris B, Littleton J. (2001). "Acamprosate is neuroprotective against glutamate-induced excitotoxicity when enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain." ''Alcoholism, Clinical and Experimental Research'' '''25''' (9): 1276-1283. PMID 11584146. Retrieved on [[March 4]], [[2007]].</ref> ===Possible neuroprotection=== In addition to its apparent ability to help patients refrain from drinking, some evidence suggests that acamprosate is [[neuroprotection|neuroprotective]] (that is, it protects [[neuron]]s from damage and death caused by effects of alcohol withdrawal and possibly other insults).<ref name="De Witte 2005"/> For example, acamprosate has been found to protect [[cell culture|cultured cells]] from damage induced by [[ischemia]] (inadequate blood flow).<ref name=Engelhard2006>{{cite journal | last = Engelhard | first = K | coauthors = Werner C, Lu H, Mollenberg O, Zieglgansberger W, Kochs E | title = The neuroprotective effect of the glutamate antagonist acamprosate following experimental cerebral ischemia. A study with the lipid peroxidase inhibitor u-101033e | journal = Anaesthesist | volume = 49 | issue = 9 | pages = 816&ndash;821 | year = 2006 | pmid=11076270}} </ref> Also, the drug protected infant hamsters from [[brain damage]] induced by injections of the toxin [[ibotenic acid]], which exacerbates [[excitotoxicity]] (the harmful overactivation of [[glutamate]] [[Receptor (biochemistry)|receptors]].<ref name=Adde2005>{{cite journal | last = Adde-Michel | first = C | coauthors = Hennebert O, Laudenbach V, Marret S, Leroux P | title = Effect of acamprosate on neonatal excitotoxic cortical lesions in in utero alcohol-exposed hamsters | journal = Neuroscience Letters | volume = 374 | issue = 2 | pages = 109&ndash;112 | year = 2005 | doi = 10.1016/j.neulet.2004.10.037 | pmid=15644274}}</ref> ==References== {{reflist|2}} {{Drugs used in addictive disorders}} [[Category:Alcohol abuse]] [[Category:Drugs]] [[Category:Sulfonic acids]] [[Category:Amides]] [[ar:أكامبروسيت]] [[de:Acamprosat]] [[nl:Acamprosaat]] [[sv:Akamprosat]]