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Vol. 50, No. 1, 2004
Issue release date: June 2004
Neuropsychobiology 2004;50:71–77

Pharmacodynamic Effects of Acamprosate on Markers of Cerebral Function in Alcohol-Dependent Subjects Administered as Pretreatment and during Alcohol Abstinence

Boeijinga P.H. · Parot P. · Soufflet L. · Landron F. · Danel T. · Gendre I. · Muzet M. · Demazières A. · Luthringer R.
aFORENAP ‘Research Institute for Neuroscience, Pharmacology and Psychiatry’, Rouffach, bConseil en Pharmacologie Clinique, Massy, cMERCK Santé, Lyon, and dCHRU, Unité de psychopathologie et alcoologie clinique de l’anxiété, Lille, France

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Animal studies suggested that acamprosate modulates neuronal hyperexcitability of acute alcohol withdrawal, acting through the glutamatergic neurotransmission. In the present study, we further investigated whether treatment with acamprosate could attenuate the post-alcohol withdrawal hyperexcitability or hyperarousal in humans using brain magnetoencephalography mapping of spontaneous fields. A double-blind, randomised, placebo-controlled study with a parallel group design comparing 2,000 mg/day of acamprosate versus placebo was conducted in alcohol-dependent subjects meeting DSM-IV criteria for alcohol dependence. Treatments were initiated 8 days before alcohol withdrawal and prolonged during the 15 following (abstinence) days. The study demonstrated that during alcohol withdrawal, acamprosate decreased the arousal level as reflected by alpha slow-wave index (ASI) measurement. This effect was mostly evidenced in left parietotemporal regions and, to a lesser extent, in the contiguous anterior, posterior and right-sided regions. In the placebo group, on the contrary, ASI measures increased between day 2 (acute withdrawal) and day 14 (prolonged withdrawal). The present results suggest a sustained effect of acamprosate on the hyperexcitability state due to alcohol withdrawal in alcohol-dependent patients and that acamprosate may have a protective effect when administered 8 days before alcohol withdrawal.

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  1. Grant KA, Lovinger DM: Cellular and behavioral neurobiology of alcohol: Receptor-mediated neuronal processes. Clin Neurosci 1995;3:155–164.
  2. Tsai G, Gastfriend DR, Coyle JT: The glutamatergic basis of human alcoholism. Am J Psychiatry 1995;152:332–340.
  3. Lhuintre JP, Daoust M, Moore ND, Chrétien P, Saligaut C, Tran G, Bosimare F, Hillemand B: Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics. Lancet 1985;i:1014–1016.
  4. Paille FM, Guelfi JD, Perkins AC, Royer RJ, Steru L, Parot P: Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol. Alcohol Alcohol 1995;30:239–247.
  5. Whitworth AB, Fischer F, Lesch OM, Nimmerrichter A, Oberbauer H, Platz T, Potgieter A, Walter H, Fleischhacker WW: Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet 1996;347:1438–1442.
  6. Sass H, Soyka M, Mann K, Zieglgansberger W: Relapse prevention by acamprosate. Results from a placebo-controlled study on alcohol dependence. Arch Gen Psychiatry 1996;53:673–680.
  7. Garbutt JC, West SL, Carey TS, Lohr KN, Crews FT: Pharmacological treatment of alcohol dependence: A review of the evidence. JAMA 1999;281:1318–1325.
  8. Mason BJ, Ownby RL: Acamprosate for the treatment of alcohol dependence: A review of double-blind, placebo-controlled trials. CNS Spectr 2000;5:58–69.
  9. De Witte P, Dahchour A, Quertemont E: Acute and chronic alcohol injections increase taurine in the nucleus accumbens. Alcohol Alcohol Suppl 1994;2:229–233.
  10. Dahchour A, De Witte P: Ethanol and amino acids in the central nervous system: Assessment of the pharmacological actions of acamprosate. Prog Neurobiol 2000;60:343–362.
  11. Zeise ML, Kasparov S, Capogna M, Zieglgansberger W: Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: Possible involvement of excitatory amino acid receptors. Eur J Pharmacol 1993;231:47–52.
  12. Spanagel R, Putzke J, Stefferl A, Schobitz B, Zieglgansberger W: Acamprosate and alcohol. 2. Effects on alcohol withdrawal in the rat. Eur J Pharmacol 1996;305:45–50.
  13. Dahchour A, De Witte P, Bolo N, Nedelec J-F, Muzet M, Durbin P, Macher J-P: Central effects of acamprosate. 1. Acamprosate blocks the glutamate increase in the nucleus accumbens microdialysate in ethanol withdrawn rats. Psychiatry Res 1998;82:107–114.
  14. Dahchour A, Quertemont E, De Witte P: Acute ethanol increases taurine but neither glutamate nor GABA in the nucleus accumbens of male rats: A microdialysis study. Alcohol Alcohol 1994;29:485–487.
  15. Naassila M, Hammoumi S, Legrand E, Durbin P, Daoust M: Mechanism of action of acamprosate. 1. Characterization of spermidine-sensitive acamprosate binding site in rat brain. Alcohol Clin Exp Res 1998;22:802–809.
  16. Al Qatari M, Bouchenafa O, Littleton J: Mechanism of action of acamprosate. 2. Ethanol dependence modifies effects of acamprosate on NMDA receptor binding in membranes from rat cerebral cortex. Alcohol Clin Exp Res 1998;22:810–814.
  17. Littleton JM, Lovinger D, Liljequist S, Ticku R, Matsumoto I, Barron S: Role of polyamines and NMDA receptors in ethanol dependence and withdrawal. Alcohol Clin Exp Res 2001;25:132S–136S.

    External Resources

  18. Harris BR, Prendergast MA, Gibson DA: Acamprosate inhibits the binding and neurotoxic effects of trans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors. Alcohol Clin Exp Res 2002;26:1779–1793.
  19. Bolo N, Nedelec JF, Muzet M, De Witte P, Dahchour A, Durbin P, Macher JP: Central effects of acamprosate. 2. Acamprosate modifies the brain in-vivo proton magnetic resonance spectrum in healthy young male volunteers. Psychiatry Res 1998;82:115–127.
  20. Fourtillan JB: Pharmacokinetics and relative bioavailabilities of acetylhomotaurinate (AOTA) after oral administration of a single dose equal to 666 mg of calcium acetylhomotaurinate (AOTA-Ca) in six young healthy volunteers, when given as aqueous solution and enteric coated tablets. Merck Santé, France, 1989, AD 864 H (data on file).
  21. Wilde MI, Wagstaff AJ: Acamprosate. A review of its pharmacology and clinical potential in the management of alcohol dependence after detoxification. Drugs 1997;53:1038–1053.
  22. Hjorth B: An on-line transformation of EEG scalp potentials into orthogonal source derivations. Electroencephalogr Clin Neurophysiol 1975;39:526–530.
  23. Matejcek M: Cortical correlates of vigilance regulation and their use in evaluating the effects of treatment. Adv Biochem Psychopharmacol 1980;23:339–348.
  24. Matejcek M: Vigilance and the EEG: Psychological, physiological and pharmacological aspects; in Herrmann WM (ed): Electroencephalography in Drug Research. Stuttgart, Fischer, 1982, pp 405–508.
  25. Ansseau M, Besson J, Lejoyeux M, Pinto E, Landry U, Cornes M, Deckers F, Potgieter A, Ades J: A French translation of the obsessive-compulsive drinking scale for craving in alcohol-dependent patients: A validation study in Belgium, France, and Switzerland. Eur Addict Res 2000;6:51–56.
  26. Spielberger CD, Gorsuch RL, Lushene RE: State-Trait Anxiety Inventory: Test Manual for Form X. Palo Alto, Consulting Psychologists Press, 1970.
  27. Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM: Assessment of alcohol withdrawal: The revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 1989;84:1353–1357.
  28. Cooley JW, Tuckey JW: An algorithm for the machine calculation of complex Fourier series. Math Comp 1965;19:297–301.
  29. Soufflet L, Toussaint M, Luthringer R, Gresser J, Minot R, Macher JP: A statistical evaluation of the main interpolation methods applied to 3-dimensional EEG mapping. Electroencephalogr Clin Neurophysiol 1991;79:393–402.
  30. Stancak AJ, Pfurtscheller G: Event-related desynchronisation of central beta-rhythms during brisk and slow self-paced finger movements of dominant and nondominant hand. Cogn Brain Res 1996;4:171–183.
  31. Saletu B, Saletu M, Grunberger J, Frey R, Anderer P, Mader R: Treatment of the alcoholic organic brain syndrome: Double-blind, placebo-controlled clinical, psychometric and electroencephalographic mapping studies with modafinil. Neuropsychobiology 1993;27:26–39.
  32. Saletu B, Saletu M, Grunberger J, Mader R: Spontaneous and drug-induced remission of alcoholic organic brain syndrome: Clinical, psychometric, and neurophysiological studies. Psychiatry Res 1983;10:59–75.
  33. Stenberg G, Sano M, Rosen I, Ingvar DH: EEG topography of acute ethanol effects in resting and activated normals. J Stud Alcohol 1994;55:645–656.
  34. Funderburk WH: Electroencephalographic studies in chronic alcoholics. Electroencephalogr Clin Neurophysiol 1949;1:369–370.
  35. Gabrielli WF Jr, Mednick SA, Volavka J, Pollock VE, Schulsinger F, Itil TM: Electroencephalograms in children of alcoholic fathers. Psychophysiology 1982;19:404–407.
  36. Pollock VE, Volavka J, Goodwin DW, Mednick SA, Gabrielli WF, Knop J, Schulsinger F: The EEG after alcohol administration in men at risk for alcoholism. Arch Gen Psychiatry 1983;40:857–861.
  37. Peniston EG, Kulkosky PJ: Alpha-theta brainwave training and beta-endorphin levels in alcoholics. Alcohol Clin Exp Res 1989;13:271–279.
  38. Peniston EG, Kulkosky PJ: Alcoholic personality and alpha-theta brainwave training. Med Psychother 1990;3:37–55.
  39. Saxby E, Peniston EG: Alpha-theta brainwave neurofeedback training: An effective treatment for male and female alcoholics with depressive symptoms. J Clin Psychol 1995;51:685–693.

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