Acamprosate

Last updated
Acamprosate
Acamprosate structure.svg
Acamprosate molecule ball.png
Clinical data
Pronunciation /əˈkæmproʊseɪt/
Trade names Campral EC
Other namesN-Acetyl homotaurine, acamprosate calcium (JAN JP), acamprosate calcium (USAN US)
AHFS/Drugs.com Monograph
Pregnancy
category
Routes of
administration 		Oral [1]
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 11% [1]
Protein binding Negligible [1]
Metabolism Nil [1]
Elimination half-life 20 h to 33 h [1]
Excretion Kidney [1]
Identifiers
  • 3-Acetamidopropane-1-sulfonic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.071.495 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C5H11NO4S
Molar mass 181.21 g·mol−1
3D model (JSmol)
  • [Ca+2].O=C(NCCCS(=O)(=O)[O-])C.[O-]S(=O)(=O)CCCNC(=O)C
  • InChI=1S/2C5H11NO4S.Ca/c2*1-5(7)6-3-2-4-11(8,9)10;/h2*2-4H2,1H3,(H,6,7)(H,8,9,10);/q;;+2/p-2 Yes check.svgY
  • Key:BUVGWDNTAWHSKI-UHFFFAOYSA-L Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Acamprosate, sold under the brand name Campral, is a medication which reduces alcoholism cravings. [1] [3] It is thought to stabilize chemical signaling in the brain that would otherwise be disrupted by alcohol withdrawal. [4] When used alone, acamprosate is not an effective therapy for alcohol use disorder in most individuals, [5] as it only addresses withdrawal symptoms and not psychological dependence. It facilitates a reduction in alcohol consumption as well as full abstinence when used in combination with psychosocial support or other drugs that address the addictive behavior. [3] [6] [7]

Contents

Serious side effects include allergic reactions, abnormal heart rhythms, and low or high blood pressure, while less serious side effects include headaches, insomnia, and impotence. [8] Diarrhea is the most common side-effect. [9] It is unclear if use is safe during pregnancy. [10] [11]

It is on the World Health Organization's List of Essential Medicines. [12]

Medical uses

Acamprosate is useful when used along with counseling in the treatment of alcohol use disorder. [3] Over three to twelve months it increases the number of people who do not drink at all and the number of days without alcohol. [3] It appears to work as well as naltrexone for maintenance of abstinence from alcohol, [13] however naltrexone works slightly better for reducing alcohol cravings and heavy drinking, [14] and acamprosate tends to work more poorly outside of Europe where treatment services are less robust. [15]

Contraindications

Acamprosate is primarily removed by the kidneys. A dose reduction is suggested in those with moderately impaired kidneys (creatinine clearance between 30 mL/min and 50 mL/min). [1] [16] It is also contraindicated in those who have a strong allergic reaction to acamprosate calcium or any of its components. [16]

Adverse effects

The US label carries warnings about increases of suicidal behavior, major depressive disorder, and kidney failure. [1]

Adverse effects that caused people to stop taking the drug in clinical trials included diarrhea, nausea, depression, and anxiety. [1]

Potential adverse effects include headache, stomach pain, back pain, muscle pain, joint pain, chest pain, infections, flu-like symptoms, chills, heart palpitations, high blood pressure, fainting, vomiting, upset stomach, constipation, increased appetite, weight gain, edema, sleepiness, decreased sex drive, impotence, forgetfulness, abnormal thinking, abnormal vision, distorted sense of taste, tremors, runny nose, coughing, difficulty breathing, sore throat, bronchitis, and rashes. [1]

Pharmacology

Acamprosate calcium Acamprosate Calcium Structural Formulae.png
Acamprosate calcium

Pharmacodynamics

The pharmacodynamics of acamprosate are complex and not fully understood; [17] [18] [19] however, it is believed to act as an NMDA receptor antagonist and positive allosteric modulator of GABAA receptors. [18] [19]

Its activity on those receptors is indirect, unlike that of most other agents used in this context. [20] An inhibition of the GABA-B system is believed to cause indirect enhancement of GABAA receptors. [20] The effects on the NMDA complex are dose-dependent; the product appears to enhance receptor activation at low concentrations, while inhibiting it when consumed in higher amounts, which counters the excessive activation of NMDA receptors in the context of alcohol withdrawal. [21]

The product also increases the endogenous production of taurine. [21]

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., they act as positive allosteric modulators at these receptors). [18] [5] In alcohol use disorder, one of the main mechanisms of tolerance is attributed to GABAA receptors becoming downregulated (i.e. these receptors become less sensitive to GABA). [5] 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, leading to physical withdrawal symptoms; [5] since GABA normally inhibits neural firing, GABAA receptor desensitization results in unopposed excitatory neurotransmission (i.e., fewer inhibitory postsynaptic potentials occur through GABAA receptors), leading to neuronal over-excitation (i.e., more action potentials in the postsynaptic neuron). One of acamprosate's mechanisms of action is the enhancement of GABA signaling at GABAA receptors via positive allosteric receptor modulation. [18] [19] 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 liable for dependence than benzodiazepines. Acamprosate has been successfully used to control tinnitus, hyperacusis, ear pain, and inner ear pressure during alcohol use due to spasms of the tensor tympani muscle.[ medical citation needed ]

In addition, alcohol also inhibits the activity of N-methyl-D-aspartate receptors (NMDARs). [22] [23] 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. [24] Withdrawal from alcohol induces a surge in release of excitatory neurotransmitters like glutamate, which activates NMDARs. [25] Acamprosate reduces this glutamate surge. [26] The drug also protects cultured cells from excitotoxicity induced by ethanol withdrawal [27] and from glutamate exposure combined with ethanol withdrawal. [28]

The substance also helps re-establish a standard sleep architecture by normalizing stage 3 and REM sleep phases, which is believed to be an important aspect of its pharmacological activity. [21]

Pharmacokinetics

Acamprosate is not metabolized by the human body. [19] Acamprosate's absolute bioavailability from oral administration is approximately 11%, [19] and its bioavailability is decreased when taken with food. [29] Following administration and absorption of acamprosate, it is excreted unchanged (i.e., as acamprosate) via the kidneys. [19]

Its absorption and elimination are very slow, with a tmax of 6 hours and an elimination half life of over 30 hours. [20]

History

Acamprosate was developed by Lipha, a subsidiary of Merck KGaA. [30] and was approved for marketing in Europe in 1989.[ citation needed ]

In October 2001 Forest Laboratories acquired the rights to market the drug in the US. [30] [31]

It was approved by the FDA in July 2004. [32]

The first generic versions of acamprosate were launched in the US in 2013. [33]

As of 2015, acamprosate was in development by Confluence Pharmaceuticals as a potential treatment for fragile X syndrome. The drug was granted orphan status for this use by the FDA in 2013 and by the EMA in 2014. [34]

Society and culture

Acamprosate is the INN and BAN for this substance. Acamprosate calcium is the USAN and JAN. It is also technically known as N-acetylhomotaurine or as calcium acetylhomotaurinate.

It is sold under the brand name Campral. [1]

Research

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 the effects of alcohol withdrawal, and possibly other causes of neurotoxicity). [26] [35]

Some struggle to take the full course of medication (2 tablets, 3 times a day), which makes acamprosate less effective. Standard support to help people take their medication involves monthly check-ins with addiction services or a GP. Research found that compared to standard support alone, extra telephone support by a pharmacist, plus financial incentives, increased the numbers who took medication as prescribed and was cost-effective. The same telephone support without financial incentives did not significantly increase the numbers taking their medication as prescribed and was less cost-effective. [36] [37]

Related Research Articles

<span class="mw-page-title-main">Alcoholism</span> Problematic excessive alcohol consumption

Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records, the World Health Organization (WHO) estimated there were 283 million people with alcohol use disorders worldwide as of 2016. The term alcoholism was first coined in 1852, but alcoholism and alcoholic are stigmatizing and discourage seeking treatment, so clinical diagnostic terms such as alcohol use disorder or alcohol dependence are used instead.

<span class="mw-page-title-main">Benzodiazepine</span> Class of depressant drugs

Benzodiazepines, colloquially called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and was made available in 1960 by Hoffmann–La Roche, who soon followed with diazepam (Valium) in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.

<span class="mw-page-title-main">Diazepam</span> Benzodiazepine sedative

Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken orally, as a suppository inserted into the rectum, intramuscularly, intravenously or used as a nasal spray. When injected intravenously, effects begin in one to five minutes and last up to an hour. Orally, effects begin after 15 to 60 minutes.

<span class="mw-page-title-main">Alprazolam</span> Benzodiazepine medication

Alprazolam, sold under the brand name Xanax, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly used in management of anxiety disorders, specifically panic disorder or generalized anxiety disorder (GAD). Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is generally taken orally.

<span class="mw-page-title-main">Zolpidem</span> Hypnotic medication

Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavioral changes, such as sleep hygiene, have been tried. It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray.

Colloquially known as "downers", depressants or central depressants are drugs that lower neurotransmission levels, or depress or reduce arousal or stimulation in various areas of the brain. Depressants do not change the mood or mental state of others. Stimulants, or "uppers", increase mental or physical function, hence the opposite drug class from depressants are stimulants, not antidepressants.

<span class="mw-page-title-main">Baclofen</span> Medication for muscle movement disorders

Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life, and off-label to treat alcohol use disorder or opioid withdrawal symptoms. It is taken orally or by intrathecal pump. It is also sometimes used transdermally in combination with gabapentin and clonidine prepared at a compounding pharmacy.

<span class="mw-page-title-main">Naltrexone</span> Medication

Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol use or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found effective in the treatment of other addictions and may be used for them off-label. An opioid-dependent person should not receive naltrexone before detoxification. It is taken by mouth or by injection into a muscle. Effects begin within 30 minutes, though a decreased desire for opioids may take a few weeks to occur. Side effects may include trouble sleeping, anxiety, nausea, and headaches. In those still on opioids, opioid withdrawal may occur. Use is not recommended in people with liver failure. It is unclear if use is safe during pregnancy. Naltrexone is an opioid antagonist and works by blocking the effects of opioids, including both opioid drugs as well as opioids naturally produced in the brain.

<span class="mw-page-title-main">Flurazepam</span> Hypnotic medication

Flurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days. Flurazepam was patented in 1968 and came into medical use the same year. Flurazepam, developed by Roche Pharmaceuticals, was one of the first benzodiazepine hypnotic medications to be marketed.

Neuropharmacology is the study of how drugs affect function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain. Molecular neuropharmacology involves the study of neurons and their neurochemical interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central and peripheral nervous systems. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, psychological disorders, addiction, and many others.

<span class="mw-page-title-main">Clobazam</span> Benzodiazepine class medication

Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselective anxiolytic since 1970, and an anticonvulsant since 1984. The primary drug-development goal was to provide greater anxiolytic, anti-obsessive efficacy with fewer benzodiazepine-related side effects.

<span class="mw-page-title-main">Clorazepate</span> Benzodiazepine medication

Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiazepine and serves as a prodrug for the equally long-lasting desmethyldiazepam, which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.

<span class="mw-page-title-main">Adinazolam</span> Triazolobenzodiazepine drug

Adinazolam is a tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It possesses anxiolytic, anticonvulsant, sedative, and antidepressant properties. Adinazolam was developed by Jackson B. Hester, who was seeking to enhance the antidepressant properties of alprazolam, which he also developed. Adinazolam was never FDA approved and never made available to the public market; however, it has been sold as a designer drug.

<span class="mw-page-title-main">Bretazenil</span> Chemical compound

Bretazenil (Ro16-6028) is an imidazopyrrolobenzodiazepine anxiolytic drug which is derived from the benzodiazepine family, and was invented in 1988. It is most closely related in structure to the GABA antagonist flumazenil, although its effects are somewhat different. It is classified as a high-potency benzodiazepine due to its high affinity binding to benzodiazepine binding sites where it acts as a partial agonist. Its profile as a partial agonist and preclinical trial data suggests that it may have a reduced adverse effect profile. In particular bretazenil has been proposed to cause a less strong development of tolerance and withdrawal syndrome. Bretazenil differs from traditional 1,4-benzodiazepines by being a partial agonist and because it binds to α1, α2, α3, α4, α5 and α6 subunit containing GABAA receptor benzodiazepine receptor complexes. 1,4-benzodiazepines bind only to α1, α2, α3 and α5GABAA benzodiazepine receptor complexes.

<span class="mw-page-title-main">Benzodiazepine withdrawal syndrome</span> Signs and symptoms due to benzodiazepines discontinuation in physically dependent persons

Benzodiazepine withdrawal syndrome is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stops taking them without a safe taper schedule.

<span class="mw-page-title-main">GABRA2</span> Protein in humans

Gamma-aminobutyric acid receptor subunit alpha-2 is a protein in humans that is encoded by the GABRA2 gene.

<span class="mw-page-title-main">Alcohol withdrawal syndrome</span> Medical condition

Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. More severe symptoms may include seizures, and delirium tremens (DTs); which can be fatal in untreated patients. Symptoms start at around 6 hours after last drink. Peak incidence of seizures occurs at 24-36 hours and peak incidence of delirium tremens is at 48-72 hours.

<span class="mw-page-title-main">Short-term effects of alcohol consumption</span> Overview of the short-term effects of the consumption of alcoholic beverages

The short-term effects of alcohol consumption range from a decrease in anxiety and motor skills and euphoria at lower doses to intoxication (drunkenness), to stupor, unconsciousness, anterograde amnesia, and central nervous system depression at higher doses. Cell membranes are highly permeable to alcohol, so once it is in the bloodstream, it can diffuse into nearly every cell in the body.

<span class="mw-page-title-main">Benzodiazepine dependence</span> Medical condition

Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, the continued use seems to be typically associated with the avoidance of unpleasant withdrawal reaction rather than with the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, often without the described drug seeking behavior and tolerance.

Kindling due to substance withdrawal is the neurological condition which results from repeated withdrawal episodes from sedative–hypnotic drugs such as alcohol and benzodiazepines.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 "Campral label" (PDF). FDA. January 2012. Retrieved 27 November 2017. For label updates see FDA index page for NDA 021431
  2. ↑ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  3. 1 2 3 4 Plosker GL (July 2015). "Acamprosate: A Review of Its Use in Alcohol Dependence". Drugs. 75 (11): 1255–1268. doi:10.1007/s40265-015-0423-9. PMID   26084940. S2CID   19119078.
  4. ↑ Williams SH (November 2005). "Medications for treating alcohol dependence". American Family Physician. 72 (9): 1775–1780. PMID   16300039. Archived from the original on 2007-09-29. Retrieved 2006-11-29.
  5. 1 2 3 4 Malenka RC, Nestler EJ, Hyman SE, Holtzman DM (2015). "Chapter 16: Reinforcement and Addictive Disorders". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (3rd ed.). New York: McGraw-Hill Medical. ISBN   978-0-07-182770-6. It has been hypothesized that long-term ethanol exposure alters the expression or activity of specific GABAA receptor subunits in discrete brain regions. Regardless of the underlying mechanism, ethanol-induced decreases in GABAA receptor sensitivity are believed to contribute to ethanol tolerance, and also may mediate some aspects of physical dependence on ethanol. ... Detoxification from ethanol typically involves the administration of benzodiazepines such as chlordiazepoxide, which exhibit cross-dependence with ethanol at GABAA receptors (Chapters 5 and 15). A dose that will prevent the physical symptoms associated with withdrawal from ethanol, including tachycardia, hypertension, tremor, agitation, and seizures, is given and is slowly tapered. Benzodiazepines are used because they are less reinforcing than ethanol among alcoholics. Moreover, the tapered use of a benzodiazepine with a long half-life makes the emergence of withdrawal symptoms less likely than direct withdrawal from ethanol. ... Unfortunately, acamprosate is not adequately effective for most alcoholics.
  6. ↑ Mason BJ (2001). "Treatment of alcohol-dependent outpatients with acamprosate: a clinical review". The Journal of Clinical Psychiatry. 62 (Suppl 20): 42–48. PMID   11584875.
  7. ↑ Nutt DJ, Rehm J (January 2014). "Doing it by numbers: a simple approach to reducing the harms of alcohol". Journal of Psychopharmacology. 28 (1): 3–7. doi:10.1177/0269881113512038. PMID   24399337. S2CID   36860967.
  8. ↑ "Acamprosate". drugs.com. 2005-03-25. Archived from the original on 22 December 2006. Retrieved 2007-01-08.
  9. ↑ 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): 1038–1053. doi:10.2165/00003495-199753060-00008. PMID   9179530. S2CID   195691152.
  10. ↑ "Acamprosate (Campral) Use During Pregnancy". Drugs.com.
  11. ↑ Haber P, Lintzeris N, Proude E, Lopatko O. "Guidelines for the Treatment of Alcohol Problems" (PDF). Australian Government Department of Health and Ageing. Retrieved 20 February 2023.
  12. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  13. ↑ Kranzler HR, Soyka M (August 2018). "Diagnosis and Pharmacotherapy of Alcohol Use Disorder: A Review". JAMA. 320 (8): 815–824. doi:10.1001/jama.2018.11406. PMC   7391072 . PMID   30167705.
  14. ↑ Maisel NC, Blodgett JC, Wilbourne PL, Humphreys K, Finney JW (February 2013). "Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?". Addiction. 108 (2): 275–293. doi:10.1111/j.1360-0443.2012.04054.x. PMC   3970823 . PMID   23075288.
  15. ↑ Donoghue K, Elzerbi C, Saunders R, Whittington C, Pilling S, Drummond C (June 2015). "The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta-analysis". Addiction. 110 (6): 920–930. doi:10.1111/add.12875. PMID   25664494.
  16. 1 2 Saivin S, Hulot T, Chabac S, Potgieter A, Durbin P, Houin G (November 1998). "Clinical pharmacokinetics of acamprosate". Clinical Pharmacokinetics. 35 (5): 331–345. doi:10.2165/00003088-199835050-00001. PMID   9839087. S2CID   34047050.
  17. ↑ "Acamprosate: Biological activity". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 26 November 2017. Due to the complex nature of this drug's MMOA, and a paucity of well defined target affinity data, we do not map to a primary drug target in this instance.
  18. 1 2 3 4 "Acamprosate: Summary". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 26 November 2017. Acamprosate is a NMDA glutamate receptor antagonist and a positive allosteric modulator of GABAA receptors.
    Marketed formulations contain acamprosate calcium
  19. 1 2 3 4 5 6 "Acamprosate". DrugBank. University of Alberta. 19 November 2017. Retrieved 26 November 2017. Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcoholism, possibly by blocking glutaminergic N-methyl-D-aspartate receptors, while gamma-aminobutyric acid type A receptors are activated. ... The mechanism of action of acamprosate in the maintenance of alcohol abstinence is not completely understood. Chronic alcohol exposure is hypothesized to alter the normal balance between neuronal excitation and inhibition. in vitro and in vivo studies in animals have provided evidence to suggest acamprosate may interact with glutamate and GABA neurotransmitter systems centrally, and has led to the hypothesis that acamprosate restores this balance. It seems to inhibit NMDA receptors while activating GABA receptors.
  20. 1 2 3 Kalk NJ, Lingford-Hughes AR (February 2014). "The clinical pharmacology of acamprosate". British Journal of Clinical Pharmacology. 77 (2): 315–323. doi:10.1111/bcp.12070. PMC   4014018 . PMID   23278595.
  21. 1 2 3 Mason BJ, Heyser CJ (March 2010). "Acamprosate: a prototypic neuromodulator in the treatment of alcohol dependence". CNS & Neurological Disorders Drug Targets. 9 (1): 23–32. doi:10.2174/187152710790966641. PMC   2853976 . PMID   20201812.
  22. ↑ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 372. ISBN   978-0-07-148127-4.
  23. ↑ Möykkynen T, Korpi ER (July 2012). "Acute effects of ethanol on glutamate receptors". Basic & Clinical Pharmacology & Toxicology. 111 (1): 4–13. doi: 10.1111/j.1742-7843.2012.00879.x . PMID   22429661.
  24. ↑ Tsai G, Coyle JT (1998). "The role of glutamatergic neurotransmission in the pathophysiology of alcoholism". Annual Review of Medicine. 49: 173–184. doi:10.1146/annurev.med.49.1.173. PMID   9509257.
  25. ↑ Tsai GE, Ragan P, Chang R, Chen S, Linnoila VM, Coyle JT (June 1998). "Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal". The American Journal of Psychiatry. 155 (6): 726–732. PMID   9619143.
  26. 1 2 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. doi:10.2165/00023210-200519060-00004. PMID   15963001. S2CID   11563216.
  27. ↑ Mayer S, Harris BR, Gibson DA, Blanchard JA, Prendergast MA, Holley RC, Littleton J (October 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. doi:10.1097/00000374-200210000-00003. PMID   12394279.
  28. ↑ al Qatari M, Khan S, Harris B, Littleton J (September 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. doi:10.1111/j.1530-0277.2001.tb02348.x. PMID   11584146.
  29. ↑ Trevor AJ (2017). "The Alcohols". In Katzung BG (ed.). Basic & Clinical Pharmacology (14th ed.). New York: McGraw-Hill. ISBN   978-1-259-64115-2. OCLC   1015240036.
  30. 1 2 Berfield S (27 May 2002). "A CEO and His Son". Bloomberg Businessweek.
  31. ↑ "Press release: Forest Laboratories Announces Agreement For Alcohol Addiction Treatment". Forest Labs via Evaluate Group. October 23, 2001.
  32. ↑ "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.
  33. ↑ "Acamprosate generics". DrugPatentWatch. Archived from the original on 1 December 2017. Retrieved 27 November 2017.
  34. ↑ "Acamprosate - Confluence Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG. Retrieved 27 November 2017.
  35. ↑ Mann K, Kiefer F, Spanagel R, Littleton J (July 2008). "Acamprosate: recent findings and future research directions". Alcoholism: Clinical and Experimental Research. 32 (7): 1105–1110. doi:10.1111/j.1530-0277.2008.00690.x. PMID   18540918.
  36. ↑ Donoghue K, Boniface S, Brobbin E, Byford S, Coleman R, Coulton S, Day E, Dhital R, Farid A, Hermann L, Jordan A, Kimergård A, Koutsou ML, Lingford-Hughes A, Marsden J (2023-10-30). "Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT". Health Technology Assessment. 27 (22): 1–88. doi:10.3310/DQKL6124. ISSN   2046-4924. PMC   10641712 . PMID   37924307.
  37. ↑ "Alcohol dependence: telephone support plus financial incentives helped people take acamprosate". NIHR Evidence. 20 February 2024. doi:10.3310/nihrevidence_62108.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.