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Acamprosate Mechanism Of Action

Acamprosate Mechanism Of Action

Acamprosate Mechanism

Mechanism of action of acamprosate. Part II. Ethanol dependence modifies effects of acamprosate on NMDA receptor binding in membranes from rat cerebral cortex.

Acamprosate is a putative anticraving drug used to maintain abstinence in alcohol-dependent patients. Its mechanism of action is uncertain, but the drug is thought to interact with neuronal NMDA receptors and calcium channels, and these proteins are implicated in the induction of alcohol dependence. In these experiments, the effects of acamprosate were studied on the binding of the NMDA receptor ligand [3H]dizocilpine to rat brain membranes under nonequilibrium conditions; 10 microM glutamate and 1 microM glycine were present in the binding assays to partially activate the receptor.

whereas at higher concentrations binding was inhibited. This effect is consistent with a partial agonist effect of acamprosate on the NMDA receptor protein. However, when rats were made dependent on ethanol (exposure to the drug for 10 days by inhalation) and cortical membranes were prepared from these animals, acamprosate in vitro no longer produced any enhancement of [3H]dizocilpine binding. Similar results were obtained when membranes were used from rats that had received 400 mg/kg/day of acamprosate in their drinking water with or without concurrent ethanol inhalation for 10 days. Thus, in brain membranes from all these treatment groups, acamprosate in vitro caused inhibition of [3H]dizocilpine binding only.

 The results suggest that acamprosate may have excitatory or inhibitory effects on NMDA receptors, depending on the experimental conditions. The effects of the drug on this system appear to be shifted toward inhibition in alcohol dependence, and this finding may be important to its clinical mechanism.

Acamprosate in Alcohol Dependence: Implications of a Unique Mechanism of Action

Acamprosate, in combination with psychosocial therapy, has been shown to be clinically effective in maintaining abstinence in alcohol dependence. Current research suggests that its mechanism of action involves functional antagonism of the ionotropic glutamate N-methyl-d-aspartate (NMDA) receptor. However, direct interactions between acamprosate and the NMDA receptor are weak, and recent findings suggest that acamprosate may modulate NMDA receptors via regulatory polyamine sites, or that it may act directly on metabotropic glutamate receptors.

All of these mechanisms are novel for the treatment of alcohol dependence and have far-reaching implications for understanding relapse, as well as for the discovery of drugs with greater efficacy. Understanding the mechanism of action of acamprosate may be an important stimulus for change in the perception and treatment of alcohol dependence.

By updating John Littleton's work published 15 years ago this review summarizes recent work on pharmacodynamic aspects of acamprosate and the perspective for future developments. In addition to insights into the role of glutamatergic receptor systems, craving and relapse inspired by acamprosate, clinical research points towards one question: if we knew how acamprosate works, we might also be able to generate hypotheses, for whom it does work.

 Recent research on acamprosate tightly links pre-clinical and clinical research that includes molecular biology, animal models, pharmacogenetic and imaging genetic trials, and clinical efficacy studies. To increase the efficacy of this drug, targeted treatment and individualized therapy approaches seem useful and necessary.

Acamprosate in alcohol dependence: implications of a unique mechanism of action.

Acamprosate, in combination with psychosocial therapy, has been shown to be clinically effective in maintaining abstinence in alcohol dependence. Current research suggests that its mechanism of action involves functional antagonism of the ionotropic glutamate N-methyl-d-aspartate (NMDA) receptor.

However, direct interactions between acamprosate and the NMDA receptor are weak, and recent findings suggest that acamprosate may modulate NMDA receptors via regulatory polyamine sites, or that it may act directly on metabotropic glutamate receptors. All of these mechanisms are novel for the treatment of alcohol dependence and have far-reaching implications for understanding relapse, as well as for the discovery of drugs with greater efficacy. Understanding the mechanism of action of acamprosate may be an important stimulus for change in the perception and treatment of alcohol dependence.

Approved by the FDA in 2004 for the use in alcohol-dependent individuals, the effectiveness of acamprosate was first demonstrated in Europe. Acamprosate is available for oral administration in a delayed-release oral formula under the brand Campral. Acamprosate is the calcium salt of N-acetyl homotaurine, which bears many structural similarities to the amino acids glutamate, GABA, glycine and taurine, all of which have activity in the CNS as neurotransmitters or neuromodulators.

There is no consensus on the primary mechanism of action of acamprosate, but alternative models suggest that acamprosate may antagonize the NMDA glutamate receptor,modulate neurotransmission through Type 5 metabotropic glutamate receptors and reduce accumulation of glutamate during repeated episodes of alcohol withdrawal.

While the preferred method for treating many substance addictions is a programme of detoxification followed by rehabilitation, there are certain medications that can be used in conjunction with counselling and therapy to improve results.

For example, some medications can be administered during detox as a replacement drug to help relieve the symptoms of withdrawal. Taking such a substitute drug in tapering doses can help to prevent some of the worst symptoms of withdrawal from occurring or reduce the severity of those that do occur.

Some medications can also be prescribed for use after detox to help prevent a relapse. When it comes to abuse and addiction, there are many types of medication that can help to reduce cravings. Then there are others that decrease the pleasurable effects of certain substances, making it less enjoyable to u se them.

Although the exact mechanism of action of Acamprosate is not fully understood at the time of this writing, it is thought that, because chronic alcohol abuse alters the balance of certain chemicals in the brain, Acamprosate can restore this balance. Scientists think that Acamprosate does this by interacting with the GABA and glutamate neurotransmitter systems.

It is thought that it inhibits NMDA receptors and activates GABA receptors and in so doing can restore the normal balance of inhibition and neuronal excitation that is affected by chronic alcohol abuse.

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