Open Access Articles- Top Results for Acamprosate


File:Acamprosate structure.svg
Systematic (IUPAC) name
3-Acetamidopropane-1-sulfonic acid
Clinical data
Oral (333mg tablets of acamprosate calcium)[1]
Pharmacokinetic data
Bioavailability 11%[1]
Protein binding Negligible[1]
Metabolism Nil[1]
Half-life 20 to 33 hours[1]
Excretion Renal[1]
77337-76-9 7pxY
PubChem CID 155434
DrugBank DB00659 7pxY
ChemSpider 136929 7pxY
KEGG D07058 7pxY
ChEBI CHEBI:51042 7pxY
ChEMBL CHEMBL1201293 7pxN
Chemical data
Formula C5H11NO4S
181.211 g/mol
 14pxN (what is this?)  (verify)

Acamprosate (INN, BAN) (brand name Campral), or acamprosate calcium (USAN, JAN), also known as N-acetylhomotaurine or as calcium acetylhomotaurinate,[2] is a drug used for treating alcohol and benzodiazepine dependence.

Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcohol withdrawal or benzodiazepine withdrawal.[3] Reports indicate that acamprosate works[clarification needed] only with a combination of attending support groups and abstinence from alcohol.[4][5] Certain serious side effects include diarrhea, allergic reactions, irregular heartbeats, and low or high blood pressure, while less serious side effects include headaches, insomnia, and impotence.[6] Diarrhea is the most common side-effect. [7] Acamprosate should not be taken by people with kidney problems or allergies to the drug.[8]

Until it became a generic in the United States, Campral was manufactured and marketed in the United States by Forest Laboratories, while Merck KGaA markets it outside the US. It is sold as 333 mg white and odorless tablets of acamprosate calcium, which is the equivalent of 300 mg of acamprosate.[1]


The mechanism of action of acamprosate is unknown and controversial.[9] At high concentrations, well above those that occur clinically (1–3 μM), reports of inhibition of glutamate receptor-activated responses (1 mM), enhancement of NMDA receptor function (300 μM), weak antagonization of the NMDA receptor, partial agonism of the polyamine site of the NMDA receptor, and possible inhibition of the mGluR1 and mGluR5 (10 μM) have all been published.[9] However, no direct action of acamprosate at clinically-relevant concentrations has yet been reported. Moreover, a subsequent study found no action of acamprosate on the mGluR1 or mGluR5 at concentrations as high as 100 μM, nor at GABAA or glycine receptors or voltage-gated sodium channels.[9]


Ethanol and benzodiazepines act on the central nervous system by binding to the GABAA receptor, increasing the effects of the inhibitory neurotransmitter GABA (i.e., it is a positive allosteric modulator). In chronic alcohol abuse, one of the main mechanisms of tolerance is attributed to GABAA receptors becoming downregulated (i.e. becoming generally less sensitive to the inhibitory effect of the GABA system). When alcohol is no longer consumed, these down-regulated GABAA receptor complexes are so insensitive to GABA that the typical amount of GABA produced has little effect; compounded with the fact that GABA normally inhibits action potential formation, there are not as many receptors for GABA to bind to — meaning that sympathetic activation is unopposed, leading to sympathetic over-stimulation. Acamprosate's mechanism of action is supposed to be, at least partially, due to an enhancement effect on GABA receptors. It has been purported to open the chloride ion channel in a novel way as it does not require GABA as a cofactor, making it less addictive than benzodiazepines. Its mode of action is similar to methocarbamol as it also does not require GABA as a cofactor. Thus, down regulation of the GABAA receptor is rare with methocarbamol and acamprosate. Methocarbamol only has a two-hour half-life, and so it is not useful in long-term therapy like acamprosate is with a long 33 hour half life. Acamprosate has been successfully used to control tinnitus, hyperacusis, ear pain and inner ear pressure during alcohol and benzodiazepine withdrawal due to spasms of the tensor tympani muscle.[citation needed]


In addition, alcohol also inhibits the activity of N-methyl-D-aspartate receptors (NMDARs). Chronic alcohol consumption leads to the overproduction (upregulation) of these receptors. Thereafter, sudden alcohol abstinence causes the excessive numbers of NMDARs to be more active than normal and to contribute to the symptoms of delirium tremens and excitotoxic neuronal death.[10] Withdrawal from alcohol induces a surge in release of excitatory neurotransmitters like glutamate, which activates NMDARs.[11] Acamprosate reduces this glutamate surge.[12] The drug also protects cultured cells from excitotoxicity induced by ethanol and benzodiazepine withdrawal[13] and from glutamate exposure combined with ethanol withdrawal.[14]

A study at Cedars-Sinai Medical Center's Brain Research Institute suggested that acamprosate might be efficacious treating nicotine addiction in humans.[15]


In contrast to the traditionally wide array of purported mechanisms of action (as described previously), a 2013 profile animal study published in Neuropsychopharmacology[16] suggests that acamprosate has by itself no psychotropic profile, no N-methyl-D-aspartate receptor or metabotropic glutamate receptor 5 activity, and that therapeutic effects are due to the active calcium moiety co-administered with the acamprosate salt form. These findings have not yet been reproduced.

Neuroprotective effects

In addition to its apparent ability to help patients refrain from drinking and aid in tapering benzodiazepines, some evidence suggests that acamprosate is neuroprotective (that is, it protects neurons from damage and death caused by the effects of alcohol and benzodiazepine withdrawal, and possibly other causes of neurotoxicity).[2][12] For example, acamprosate has been found to protect cultured cells from damage induced by ischemia (inadequate blood flow).[17] The drug also protected infant hamsters from brain damage induced by injections of the toxin ibotenic acid (which exacerbates excitotoxicity, the harmful over-activation of glutamate receptors).[18]

One Brazilian study has shown that acamprosate may be an effective treatment for tinnitus (persistent ringing in the ears due to hearing loss or benzodiazepine withdrawal).[19]


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 studies involving alcohol-dependent patients who had already been withdrawn from alcohol, (i.e., 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 addicting and was generally well tolerated in clinical trials. The most common adverse events reported for patients taking Campral included headache, diarrhea, flatulence, and nausea.[20]

Clinical study results

The Scripps Research Institute conducted a double blind study comparing acamprosate and placebos, in combination with psychotherapy, in the effectiveness of treating alcohol dependence. The researchers concluded that acamprosate is “safe and effective” as acamprosate increased the percentage of alcohol-free days.[21]

Another study was conducted by Princess Alexandra Hospital in Brisbane comparing the use of acamprosate, naltrexone, or both drugs at once (with each pharmacological treatment also paired with cognitive behavioral therapy) in a 12-week study.[22] This study concluded that a combination of medications was generally more popular and yielded better results than using either drug alone, as outlined below.

Percentage attending program Abstinence rates Average number of days abstinence1 Days until first breach of abstinence1

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
1 This statistic applies to patients who could not remain abstinent throughout the entire 84-day period.


Acamprosate is primarily removed by the kidneys and should not be given to people with severely impaired kidneys (creatinine clearance less than 30ml/min). A dose reduction is suggested in those with moderately impaired kidneys (creatinine clearance between 30ml/min and 50ml/min). [23][24] It is also contraindicated in those who have a strong allergic reaction to acamprosate calcium or any of its components. [23] [24]


Current studies have not shown any serious drug-drug interactions between acamprosate and alcohol, diazepam, imipramine, or disulfiram. [23] One study found that giving acamprosate with naltrexone had no harmful effects and no clinically important effects on the pharmacokinetics of either drugs. [25]

See also


  1. ^ a b c d e f g h "Campral Description" (PDF). Archived from the original (PDF) on 2006-03-18. Retrieved 2006-04-02. 
  2. ^ a b Mann K, Kiefer F, Spanagel R, Littleton J (July 2008). "Acamprosate: recent findings and future research directions". Alcohol. Clin. Exp. Res. 32 (7): 1105–10. PMID 18540918. doi:10.1111/j.1530-0277.2008.00690.x. 
  3. ^ Williams, SH. (2005). "Medications for treating alcohol dependence". American Family Physician 72 (9): 1775–1780. PMID 16300039. 
  4. ^ Mason, BJ (2001). "Treatment of alcohol-dependent outpatients with acamprosate: a clinical review.". The Journal of clinical psychiatry. 62 Suppl 20: 42–8. PMID 11584875. 
  5. ^ GABA Agonist (Acamprosate) for Alcohol Treatment, Alcohol Rehab Thailand
  6. ^ "Acamprosate". 2005-03-25. Archived from the original on 22 December 2006. Retrieved 2007-01-08. 
  7. ^ Wilde, MI; Wagstaff, AJ (June 1997). "Acamprosate. A review of its pharmacology and clinical potential in the management of alcohol dependence after detoxification". Drugs 53 (6): 1038–53. PMID 9179530. doi:10.2165/00003495-199753060-00008. 
  8. ^ "Acamprosate Oral - Who should not take this medication?". Retrieved 2007-01-08. 
  9. ^ a b c Reilly, Matthew T.; Lobo, Ingrid A.; McCracken, Lindsay M.; Borghese, Cecilia M.; Gong, Diane; Horishita, Takafumi; Adron Harris, R. (2008). "Effects of Acamprosate on Neuronal Receptors and Ion Channels Expressed inXenopusOocytes". Alcoholism: Clinical and Experimental Research 32 (2): 188–196. ISSN 0145-6008. doi:10.1111/j.1530-0277.2007.00569.x. 
  10. ^ Tsai, G; Coyle, JT (1998). "The role of glutamatergic neurotransmission in the pathophysiology of alcoholism". Annual review of medicine 49: 173–84. PMID 9509257. doi:10.1146/ 
  11. ^ Tsai, GE; Ragan, P; Chang, R; Chen, S; Linnoila, VM; Coyle, JT (1998). "Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal". The American Journal of Psychiatry 155 (6): 726–32. PMID 9619143. 
  12. ^ a b 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): 517–37. PMID 15963001. doi:10.2165/00023210-200519060-00004. 
  13. ^ 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): 1468–78. PMID 12394279. doi:10.1097/01.ALC.0000033261.14548.D2. 
  14. ^ 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): 1276–83. PMID 11584146. doi:10.1111/j.1530-0277.2001.tb02348.x. 
  15. ^ Pechnick, RN; Manalo, CM; Lacayo, LM; Vit, JP; Bholat, Y; Spivak, I; Reyes, KC; Farrokhi, C (2011). "Acamprosate attenuates cue-induced reinstatement of nicotine-seeking behavior in rats". Behavioural Pharmacology 22 (3): 222–7. PMID 21522053. doi:10.1097/FBP.0b013e328345f72c. 
  16. ^ Spanagel R, Vengeliene V, Jandeleit B, Fischer WN, Grindstaff K, Zhang X, Gallop MA, Krstew EV, Lawrence AJ, Kiefer F (March 2014). "Acamprosate produces its anti-relapse effects via calcium.". Neuropsychopharmacology. 39 (4): 783–791. PMID 24081303. doi:10.1038/npp.2013.264. 
  17. ^ Engelhard, K; Werner C; Lu H; Mollenberg O; Zieglgansberger W; Kochs E (2006). "The neuroprotective effect of the glutamate antagonist acamprosate following experimental cerebral ischemia. A study with the lipid peroxidase inhibitor u-101033e". Anaesthesist 49 (9): 816–821. PMID 11076270. 
  18. ^ Adde-Michel, C; Hennebert O; Laudenbach V; Marret S; Leroux P (2005). "Effect of acamprosate on neonatal excitotoxic cortical lesions in in utero alcohol-exposed hamsters". Neuroscience Letters 374 (2): 109–112. PMID 15644274. doi:10.1016/j.neulet.2004.10.037. 
  19. ^ Azevedo AA, Figueiredo RR (2005). "Tinnitus treatment with acamprosate: double-blind study". Braz J Otorhinolaryngol 71 (5): 618–23. PMID 16612523. doi:10.1590/S0034-72992005000500012. 
  20. ^ "FDA Approves New Drug for Treatment of Alcoholism". FDA Talk Paper. Food and Drug Administration. 2004-07-29. Archived from the original on 2008-01-17. Retrieved 2009-08-15. 
  21. ^ Mason, BJ; Goodman AM; Chabac S; Lehert P (2006). "Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: The role of patient motivation". J Psychiatr Res 40 (5): 383–393. PMID 16546214. doi:10.1016/j.jpsychires.2006.02.002. 
  22. ^ Feeney, GF; Connor JP; Young RM; Tucker J; McPherson A (2006). "Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: A single centre's experience with pharmacotherapy". Alcohol Alcohol 41 (3): 321–327. PMID 16467406. doi:10.1093/alcalc/agl007. 
  23. ^ a b c Saivin, S; Hulot, T; Chabac, S; Potgieter, A; Durbin, P; Houin, G (Nov 1998). "Clinical Pharmacokinetics of Acamprosate". Clinical Pharmacokinetics 35 (5): 331–345. PMID 9839087. doi:10.2165/00003088-199835050-00001. 
  24. ^ a b "Campral Prescribing Information" (PDF). Forest Pharmaceuticals. 2004. Retrieved 28 October 2014. 
  25. ^ Mason, BJ; Goodman, AM; Dixon, RM; Hameed, MH; Hulot, T; Wesnes, K; Hunter, JA; Boyeson, MG (Oct 2002). "A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone". Neuropsychopharmacology 27 (4): 596–606. PMID 12377396. doi:10.1016/s0893-133x(02)00368-8.