Acamprosate
| File:Acamprosate structure.svg | |
| Systematic (IUPAC) name | |
|---|---|
|
3-Acetamidopropane-1-sulfonic acid | |
| Clinical data | |
| Pregnancy category | |
| Routes of administration | Oral (333mg tablets of acamprosate calcium)[1] |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 11%[1] |
| Protein binding | Negligible[1] |
| Metabolism | Nil[1] |
| Biological half-life | 20 to 33 hours[1] |
| Excretion | Renal[1] |
| Identifiers | |
| CAS Number | 77337-76-9 |
| ATC code | N07BB03 (WHO) |
| PubChem | CID 155434 |
| DrugBank | APRD00661 |
| ChemSpider | 136929 |
| Chemical data | |
| Formula | C5H11NO4S |
| Molar mass | 181.211 g/mol[[Script error: No such module "String".]] |
| Script error: No such module "collapsible list". | |
| (verify) | |
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 glutamatergic N-methyl-D-aspartate receptors, while gamma-aminobutyric acid (GABA) type A receptors are activated.[2] Reports indicate that acamprosate only works with a combination of attending support groups and abstinence from alcohol.[3] Certain serious side effects include allergic reactions, irregular heartbeats, and low or high blood pressure, while less serious side effects include headaches, insomnia, and impotence.[4] Acamprosate should not be taken by people with kidney problems or allergies to the drug.[5]
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 mg white and odorless tablets of acamprosate calcium, which is the equivalent of 300 mg of acamprosate.[1]
Contents
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and effective by multiple placebo-controlled clinical studies involving alcohol-dependent patients who had already been withdrawn from alcohol, (i.e., detoxified).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."[6]
Study results
The Scripps Research Institute conducted a double blind study comparing the effectiveness between using acamprosate and placebos in combination with psychotherapy. The primary end-point evaluated was percentage of alcohol-free days. The researchers concluded that acamprosate is "safe and effective".[7]
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.[8] 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.
| 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.
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 receptors called N-methyl-D-aspartate receptors, or NMDARs, so that chronic alcohol consumption leads to the overproduction (upregulation) 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 excitotoxic neuronal death.[9] Withdrawal from alcohol induces a surge in release of excitatory neurotransmitters like glutamate, which activates NMDARs.[10] Acamprosate reduces this glutamate surge.[11] The drug also protects cultured cells in excitotoxicity induced by ethanol withdrawal.[12] and by glutamate exposure combined with ethanol withdrawal.[13]
Possible neuroprotection
In addition to its apparent ability to help patients refrain from drinking, some evidence suggests that acamprosate is neuroprotective (that is, it protects neurons from damage and death caused by effects of alcohol withdrawal and possibly other insults).[11] For example, acamprosate has been found to protect cultured cells from damage induced by ischemia (inadequate blood flow).[14] 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 receptors.[15]
References
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sv:Akamprosat- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Campral Description" (PDF). Retrieved 2006-04-02.
- ↑ Williams SH. (2005). "Medications for treating alcohol dependence". American Family Physician 72 (9): 1775-1780. PMID 16300039
- ↑ Mason BJ. "Treatment of alcohol-dependent outpatients with acamprosate: a clinical review". J Clin Psychiatry 2001;62(suppl 20):42-8. PMID 11584875
- ↑ "Acamprosate". drugs.com. 2005-03-25. Retrieved 2007-01-08.
- ↑ "Acamprosate Oral - Who should not take this medication?". WebMD.com. Retrieved 2007-01-08.
- ↑ "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.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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- ↑ 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.
- ↑ Tsai GE, Ragan P, Chang R, Chen S, Linnoila VM, Coyle JT. (1998). "Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal." American Journal of Psychiatry, 155 (6): 726-732. PMID 9619143. Retrieved on March 4, 2007.
- ↑ 11.0 11.1 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.
- ↑ 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.
- ↑ 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.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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