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Back To Vidyya Helping Alcholics Abstain

American Trials On Acamprosate (Campral) Called "Promising"

A novel drug, already available in Europe, Asia and South America, which is designed to help alcoholics abstain from drinking has shown promise in its first round of American clinical trials.

While the drug can in no way be called a miracle cure, in the trial, those taking 2 grams a day of acamprosate didn't drink on 70 percent of the days they were studied; while those in the placebo group didn't drink for 58 percent of the days they were studied. For patients on 3 grams of acamprosate, the figure was 73 percent.

Researchers noticed that Acamprosate (Campral) worked best among those people whose goal it was to avoid alcohol entirely, rather than just cut down on their consumption. Of the 601 alcoholics in the study, only a handful, 241, had complete abstinence as their absolute goal. The patients also received psychological treatment, education and help with strategies for avoiding or stopping their consumption of alcohol.

The drug's manufacturer, Lipha SA of Lyon, France, hopes to get the drug on the American market as soon as possible. The drug will require FDA approval, which is expected to take more than a year to obtain.

Doctors already have some drugs available to maintain abstinence. One, disulfiram, makes a user feel nauseous and otherwise sick if he or she also uses alcohol. Another medication, naltrexone, acts on brain circuitry to reduce the desire to drink. Acamprosate acts on different brain circuitry.

Acamprosate's success was small. The drug helped only four percent more people abstain than did psychological counseling and placebo.

Alcoholism is a complex phenomenon, and emphasis is laid on molecular mechanisms involved in long term alcohol withdrawal and the efficacy of acamprosate (Campral). Alcohol weaning involves the activation of NMDA (N-Methyl-D-Aspartic acid) receptors. This phenomenon is partly responsible for weaning symptoms or negative enhancement via glutamate, an excitatory amino acid. This amino acid also takes part in training and memorisation processes.

While acamprosate has an inhibitory effect on glutamate-mediated hyperexcitation, it enhances glutamate synaptic transmission in the hippocampus. What may seem contradictory can be explained: campral acts as partial co-agonist. Campral adjusts the expression of the NMDA receptor according to its level of activation. Moreover, the inhibiting effect is enhanced in alcohol dependent experimental models with a high level of NMDA receptor activation.

Indeed, experiments show that once the model has become alcohol dependent, relapse can occur rapidly after a period of abstinence. Conditioning to alcohol reinforcing effects and neuroadaptation may play an important role. Campral decreases the negative reinforcement via NMDA receptors and its effect on neuroadaptation may slow down the reinstatement of physiological dependence, as shown by cellular culture models.

If one can prove that excessive glutamate transmission can induce neurotoxicity, Campral may confer a certain neuroprotection during alcohol withdrawal. Voltage-operated calcium channels also contribute to physiological dependence, and Campral reduces alcoholization-induced up-regulation. There seems to be no clinical factor predictive of the success of treatment with Campral.

Although Campral seems more efficient in the most dependent patients, the sub-group analysis of a Spanish clinical trial does not demonstrate additional effects. Motivation and the perception of the negative aspect of alcoholism remain a powerful factor in long term care. However, maintaining abstinence is independent of patients' specific characteristics.

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Editor: Susan K. Boyer, RN
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