|Trade names||Campral, Aotal, others|
|Other names||N-Acetyl homotaurine, Acamprosate calcium (JAN JP), Acamprosate calcium (USAN US)|
|Elimination half-life||20 h to 33 h|
|Chemical and physical data|
|Molar mass||181.21 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Acamprosate, sold under the brand name Campral among others, is a medication used along with counselling to treat alcohol dependence. When used alone, it is not effective for most individuals; it works best when used in combination with counselling. It is taken by mouth.
Common side effects include diarrhea and weakness. Serious side effects may include allergic reactions, mood changes, thoughts of suicide, and heart palpitations. A lower dose is recommended in people with mild kidney problems and use is not recommended in people with severe kidney disease. Use is okay in mild to moderate liver dysfunction. Safety during pregnancy is unclear. Acamprosate is thought to work by altering chemical signaling in the brain.
Acamprosate was approved for medical use in the United States in 2004. It is available as a generic medication in the United Kingdom were a month of treatment costs the NHS about 30 pounds as of 2020. This amount in the United States costs as little as 80 USD as of 2020.
Acamprosate is useful when used along with counseling in the treatment of alcohol dependence. It should be started once a person has managed to stop drinking. Over three to twelve months it increases the number of people who do not drink at all and the number of days without alcohol.
Acamprosate can be continued even if the person returns to drinking alcohol. The other medications naltrexone and disulfiram may also be used by those taking acamprosate. It appears to work as well as naltrexone.
Side effects that caused people to stop taking the drug in clinical trials included diarrhea, nausea, depression, and anxiety.
Potential side 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.
Acamprosate is primarily removed by the kidneys and should not be given to people with severely impaired kidneys (creatinine clearance less than 30 mL/min). A dose reduction is suggested in those with moderately impaired kidneys (creatinine clearance between 30 mL/min and 50 mL/min). It is also contraindicated in those who have a strong allergic reaction to acamprosate calcium or any of its components.
The pharmacodynamics of acamprosate are complex and not fully understood; however, it is believed to act as an NMDA receptor antagonist and positive allosteric modulator of GABAA receptors.
Its activity on those receptors is indirect, unlike that of most other agents used in this context. An inhibition of the GABA-B system is believed to cause indirect enhancement of GABAA receptors. The effects on the NMDA complex are dose-dependant; 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.
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). In chronic alcohol abuse, one of the main mechanisms of tolerance is attributed to GABAA receptors becoming downregulated (i.e. these receptors become less sensitive to GABA). 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; 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. 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). 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. Withdrawal from alcohol induces a surge in release of excitatory neurotransmitters like glutamate, which activates NMDARs. Acamprosate reduces this glutamate surge. The drug also protects cultured cells from excitotoxicity induced by ethanol withdrawal and from glutamate exposure combined with ethanol withdrawal.
Acamprosate is not metabolized by the human body. Acamprosate's absolute bioavailability from oral administration is approximately 11%, and its bioavailability is decreased when taken with food. Following administration and absorption of acamprosate, it is excreted unchanged (i.e., as acamprosate) via the kidneys.
It was approved by the FDA in July 2004.
The first generic versions of acamprosate were launched in the US in 2013.
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.
Society and culture
It is sold under the brand name Campral.
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).
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Unfortunately, acamprosate is not adequately effective for most alcoholics.
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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.
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Acamprosate is a NMDA glutamate receptor antagonist and a positive allosteric modulator of GABAA receptors.
Marketed formulations contain acamprosate calcium
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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 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.
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