Acamprosate in alcohol dependence: how does it work?

Acamprosate is a relatively new drug that appears to be clinically useful in the treatment of alcohol dependence. Although it has proved effective in reducing relapse into drinking in clinical trials its exact mechanism of action is uncertain. Evidence is presented that the drug does not act in any of the conventional ways to reduce alcohol intake and it is proposed that it may be a novel kind of agent that suppresses "craving". On the basis of its known pharmacological effects in pre-clinical studies it is suggested that acamprosate may reduce craving that is associated with conditioned withdrawal. In addition to the potential therapeutic value of acamprosate, the drug may be useful because work directed toward understanding its mechanism of action may shed light on some of the fundamental processes that govern alcohol abuse and relapse in weaned alcohol dependent patients.

[1]  R. Stout,et al.  The relationship between craving, anxiety, and other symptoms in opioid withdrawal. , 1992, Journal of substance abuse.

[2]  P. de Witte,et al.  Acamprosate and diazepam differentially modulate alcohol-induced behavioural and cortical alterations in rats following chronic inhalation of ethanol vapour. , 1991, Alcohol and alcoholism.

[3]  C. Johanson,et al.  Craving: consensus of status and agenda for future research. , 1992, Drug and alcohol dependence.

[4]  K. Berridge,et al.  The neural basis of drug craving: An incentive-sensitization theory of addiction , 1993, Brain Research Reviews.

[5]  P. Chrétien,et al.  ABILITY OF CALCIUM BIS ACETYL HOMOTAURINE, A GABA AGONIST, TO PREVENT RELAPSE IN WEANED ALCOHOLICS , 1985, The Lancet.

[6]  G. Koob,et al.  GABA and Nucleus Accumbens Glutamate Neurotransmission Modulate Ethanol Self‐Administration in Rats a , 1992, Annals of the New York Academy of Sciences.

[7]  D J Rohsenow,et al.  Cue reactivity in addictive behaviors: theoretical and treatment implications. , 1990, The International journal of the addictions.

[8]  N. Moore,et al.  Acamprosate appears to decrease alcohol intake in weaned alcoholics. , 1990, Alcohol and alcoholism.

[9]  J. Littleton,et al.  Current concepts of ethanol dependence. , 1994, Addiction.

[10]  J. Durlach,et al.  Lack of effects of Ca-acetyl homotaurinate on chronic and acute toxicities of ethanol in rats. , 1987, Alcohol.

[11]  K. Grant,et al.  Reinforcing and discriminative stimulus effects of Ca-acetyl homotaurine in animals , 1989, Pharmacology Biochemistry and Behavior.

[12]  R. Wise.  The neurobiology of craving: implications for the understanding and treatment of addiction. , 1988, Journal of abnormal psychology.

[13]  M. Passeri,et al.  Effects of fluoxetine and ca-acetyl-homotaurinate on alcohol intake in familial and nonfamilial alcoholic patients , 1992 .

[14]  S. Glautier,et al.  Alcohol dependence and cue reactivity. , 1994, Journal of studies on alcohol.

[15]  G. Koob,et al.  Rapid Induction of Conditioned Opiate Withdrawal in the Rat , 1993, Neuropsychopharmacology.

[16]  W. Zieglgänsberger,et al.  Calciumdiacetylhomotaurinate (CA-AOTA) decreases the action of excitatory amino acids in the rat neocortex in vitro. , 1990, Progress in clinical and biological research.

[17]  C. Heidbreder,et al.  Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats , 1992, Pharmacology Biochemistry and Behavior.

[18]  W. Zieglgänsberger,et al.  Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors. , 1993, European journal of pharmacology.

[19]  R. Ehrman,et al.  Integrating systemic cue exposure with standard treatment in recovering drug dependent patients. , 1990, Addictive behaviors.

[20]  H. Aubin,et al.  Tolérance de l'association de l'acamprosate aux médicaments du sevrage d'alcool. Essai multicentrique sur 591 alcooliques en sevrage , 1994 .

[21]  R. Ehrman,et al.  Cue reactivity and cue reactivity interventions in drug dependence. , 1993, NIDA research monograph.

[22]  J. Durlach,et al.  Dose-dependent suppression of the high alcohol intake of chronically intoxicated rats by Ca-acetyl homotaurinate. , 1987, Alcohol.

[23]  B. Nalpas,et al.  [Acamprosate. From pharmacology to therapeutics]. , 1990, L'Encephale.

[24]  R. Harris,et al.  Neurobiology of alcohol abuse. , 1992, Trends in pharmacological sciences.

[25]  P. Chrétien,et al.  A homotaurine derivative reduces the voluntary intake of ethanol by rats: are cerebral GABA receptors involved? , 1984, Pharmacology Biochemistry and Behavior.