Alcohol Use Disorders and Current Pharmacological Therapies: The Role of GABA(A) Receptors

Acta Pharmacol Sin. 2014 Aug;35(8):981-93. doi: 10.1038/aps.2014.50.

Abstract

Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABAA receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABAA receptors in the treatment of AUD and currently available and potentially novel pharmacological agents.

Publication types

  • Review

MeSH terms

  • Acamprosate
  • Alcohol Deterrents / pharmacology
  • Alcohol Deterrents / therapeutic use
  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / metabolism
  • Alcoholism / drug therapy*
  • Alcoholism / metabolism*
  • Animals
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use
  • Disulfiram / pharmacology
  • Disulfiram / therapeutic use
  • Ethanol / adverse effects
  • Ethanol / metabolism
  • Fructose / analogs & derivatives
  • Fructose / pharmacology
  • Fructose / therapeutic use
  • Humans
  • Naltrexone / pharmacology
  • Naltrexone / therapeutic use
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Plant Preparations / pharmacology
  • Plant Preparations / therapeutic use
  • Receptors, GABA-A / metabolism*
  • Taurine / analogs & derivatives
  • Taurine / pharmacology
  • Taurine / therapeutic use
  • Topiramate

Substances

  • Alcohol Deterrents
  • Narcotic Antagonists
  • Neuroprotective Agents
  • Plant Preparations
  • Receptors, GABA-A
  • Topiramate
  • Benzodiazepines
  • Taurine
  • Fructose
  • Ethanol
  • Naltrexone
  • Acamprosate
  • Disulfiram