Acamprosate
Encyclopedia
Acamprosate, also known as N-acetyl
homotaurine
and 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. Reports indicate that acamprosate only works with a combination of attending support group
s and abstinence
from alcohol
. Certain serious side effects include diarrhea
, allergic reactions, irregular heartbeats, and low or high blood pressure
, while less serious side effects include headache
s, insomnia
, and impotence. Acamprosate should not be taken by people with kidney
problems or allergies to the drug.
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 odor
less tablet
s of acamprosate calcium, which is the equivalent of 300 mg of acamprosate.
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 . Thereafter, sudden alcohol abstinence causes the excessive numbers of NMDARs to be more active than normal and to produce the symptoms of delirium tremens
and excitotoxic
neuronal death. Withdrawal
from alcohol induces a surge in release of excitatory neurotransmitter
s 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.
(that is, it protects neuron
s from damage and death caused by the effects of alcohol withdrawal, or possibly other insults). For example, acamprosate has been found to protect cultured cells
from damage induced by ischemia
(inadequate blood flow). 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
).
One Brazilian study has shown that Acamprosate may be an effective treatment for tinnitus
(persistent ringing in the ears due to hearing loss).
(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:
s, 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.
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 twelve-week study. This study concluded that a combination of medications was generally more popular and yielded better results than using either drug alone, as outlined below.
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...
homotaurine
Homotaurine
Homotaurine is a synthetic organic compound. It is analogous to taurine, but with an extra carbon in its chain. Because of its similarity in structure to the neurotransmitter gamma-aminobutyric acid , it has GABAergic effects and may be useful as an anticonvulsant.Homotaurine has also been...
and by the brand name Campral, is a drug used for treating alcohol dependence
Alcohol dependence
Alcohol dependence, as described in the DSM-IV, is a psychiatric diagnosis describing an entity in which an individual uses alcohol despite significant areas of dysfunction, evidence of physical dependence, and/or related hardship.-Definition and diagnosis:According to the DSM-IV criteria for...
.
Acamprosate is thought to stabilize the chemical balance in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
that would otherwise be disrupted by alcoholism, possibly by blocking glutamatergic N-methyl-D-aspartate receptors
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
, while gamma-aminobutyric acid
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
(GABA) type A receptors are activated. Reports indicate that acamprosate only works with a combination of attending support group
Support group
In a support group, members provide each other with various types of help, usually nonprofessional and nonmaterial, for a particular shared, usually burdensome, characteristic...
s and abstinence
Abstinence
Abstinence is a voluntary restraint from indulging in bodily activities that are widely experienced as giving pleasure. Most frequently, the term refers to sexual abstinence, or abstention from alcohol or food. The practice can arise from religious prohibitions or practical...
from alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
. Certain serious side effects include diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, allergic reactions, irregular heartbeats, and low or high blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, while less serious side effects include headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, and impotence. Acamprosate should not be taken by people with kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
problems or allergies to the drug.
Campral is manufactured and marketed in the United States by Forest Laboratories
Forest Laboratories
Forest Laboratories is a pharmaceutical company headquartered in New York City, USA. Its revenues for the year ended 31 March 2007 were US$3.4 billion. The company's research and development spending has grown rapidly in recent years, and as of 2007, approached almost a billion US dollars a year,...
, while Merck KGaA
Merck KGaA
Merck KGaA is a German chemical and pharmaceutical company. Merck, also known as “German Merck” and “Merck Darmstadt”, was founded in Darmstadt, Germany, in 1668, making it the world's oldest operating chemical and pharmaceutical company. The company was privately owned until going public in 1995...
markets it outside the US. It is sold as 333 mg white
White
White is a color, the perception of which is evoked by light that stimulates all three types of color sensitive cone cells in the human eye in nearly equal amounts and with high brightness compared to the surroundings. A white visual stimulation will be void of hue and grayness.White light can be...
and odor
Odor
An odor or odour is caused by one or more volatilized chemical compounds, generally at a very low concentration, that humans or other animals perceive by the sense of olfaction. Odors are also commonly called scents, which can refer to both pleasant and unpleasant odors...
less tablet
Tablet
A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose...
s of acamprosate calcium, which is the equivalent of 300 mg of acamprosate.
Physiological action
Delirium tremens
Delirium tremens is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813...
and excitotoxic
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...
neuronal death. Withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
from alcohol induces a surge in release of excitatory neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s like glutamate
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
, 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.
Possible neuroprotection
In addition to its apparent ability to help patients refrain from drinking, some evidence suggests that acamprosate is neuroprotectiveNeuroprotection
Neuroprotection within the nervous system protects neurons from apoptosis or degeneration, for example following a brain injury or as a result of chronic neurodegenerative diseases....
(that is, it protects neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s from damage and death caused by the effects of alcohol withdrawal, or possibly other insults). For example, acamprosate has been found to protect cultured cells
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
from damage induced by ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
(inadequate blood flow). The drug also protected infant hamsters from brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
induced by injections of the toxin ibotenic acid
Ibotenic acid
Ibotenic acid is a chemical compound that is naturally occurring in the mushrooms Amanita muscaria and Amanita pantherina, among others...
(which exacerbates excitotoxicity
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...
, the harmful over-activation of glutamate receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
).
One Brazilian study has shown that Acamprosate may be an effective treatment for tinnitus
Tinnitus
Tinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
(persistent ringing in the ears due to hearing loss).
Approval
While the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
approved this drug in July 2004, it has been legal in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
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 brainBrainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
pathways related to alcohol abuse. Campral was demonstrated to be safe and effective by multiple placeboPlaceboA placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
-controlled clinical studiesClinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
involving alcohol-dependent patients who had already been withdrawn from alcohol, (i.e., detoxifiedDrug rehabilitationDrug rehabilitation is a term for the processes of medical or psychotherapeutic treatment, for dependency on psychoactive substances such as alcohol, prescription drugs, and so-called street drugs such as cocaine, heroin or amphetamines...
). Campral proved superior to placebo in maintaining abstinenceAbstinenceAbstinence is a voluntary restraint from indulging in bodily activities that are widely experienced as giving pleasure. Most frequently, the term refers to sexual abstinence, or abstention from alcohol or food. The practice can arise from religious prohibitions or practical...
(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 addictingSubstance dependenceThe section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
and was generally well-tolerated in clinical trials. The most common adverse eventsAdverse drug reactionAn adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
reported for patients taking Campral included headacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, flatulenceFlatulenceFlatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
, and nauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
.
Clinical study results
The Scripps Research Institute conducted a double blind study comparing acamprosate and placeboPlacebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
s, in combination with psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...
, 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.
Another study was conducted by Princess Alexandra Hospital
Princess Alexandra Hospital
The Princess Alexandra Hospital , is located on Ipswich Road in Woolloongabba, Australia. It is one of the major hospitals in Brisbane and is a teaching hospital of the University of Queensland. It is a tertiary level teaching hospital with all major medical and surgical specialities onsite except...
in Brisbane
Brisbane
Brisbane is the capital and most populous city in the Australian state of Queensland and the third most populous city in Australia. Brisbane's metropolitan area has a population of over 2 million, and the South East Queensland urban conurbation, centred around Brisbane, encompasses a population of...
comparing the use of acamprosate, naltrexone
Naltrexone
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade...
, or both drugs at once (with each pharmacological treatment also paired with cognitive behavioral therapy) in a twelve-week study. 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.