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dc.contributor.authorSpanagel, Raineren
dc.contributor.authorVengeliene, Valentinaen
dc.contributor.authorJandeleit, Bernden
dc.contributor.authorFischer, Wolf-Nicolasen
dc.contributor.authorGrindstaff, Kenten
dc.contributor.authorZhang, Xuexiangen
dc.contributor.authorGallop, Mark Aen
dc.contributor.authorKrstew, Elena Ven
dc.contributor.authorLawrence, Andrew Jen
dc.contributor.authorKiefer, Falken
dc.identifier.citationNeuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology 2013; 39(4): 783-91en
dc.description.abstractAlcoholism is one of the most prevalent neuropsychiatric diseases, having an enormous health and socioeconomic impact. Along with a few other medications, acamprosate (Campral-calcium-bis (N-acetylhomotaurinate)) is clinically used in many countries for relapse prevention. Although there is accumulated evidence suggesting that acamprosate interferes with the glutamate system, the molecular mode of action still remains undefined. Here we show that acamprosate does not interact with proposed glutamate receptor mechanisms. In particular, acamprosate does not interact with NMDA receptors or metabotropic glutamate receptor group I. In three different preclinical animal models of either excessive alcohol drinking, alcohol-seeking, or relapse-like drinking behavior, we demonstrate that N-acetylhomotaurinate by itself is not an active psychotropic molecule. Hence, the sodium salt of N-acetylhomotaurinate (i) is ineffective in alcohol-preferring rats to reduce operant responding for ethanol, (ii) is ineffective in alcohol-seeking rats in a cue-induced reinstatement paradigm, (iii) and is ineffective in rats with an alcohol deprivation effect. Surprisingly, calcium salts produce acamprosate-like effects in all three animal models. We conclude that calcium is the active moiety of acamprosate. Indeed, when translating these findings to the human situation, we found that patients with high plasma calcium levels due to acamprosate treatment showed better primary efficacy parameters such as time to relapse and cumulative abstinence. We conclude that N-acetylhomotaurinate is a biologically inactive molecule and that the effects of acamprosate described in more than 450 published original investigations and clinical trials and 1.5 million treated patients can possibly be attributed to calcium.en
dc.subject.otherAlcohol Deterrents.pharmacology.therapeutic useen
dc.subject.otherAlcoholism.drug therapy.metabolismen
dc.subject.otherDisease Models, Animalen
dc.subject.otherDose-Response Relationship, Drugen
dc.subject.otherExcitatory Amino Acid Agents.pharmacologyen
dc.subject.otherExcitatory Postsynaptic Potentials.drug effectsen
dc.subject.otherGABA Agents.pharmacologyen
dc.subject.otherIn Vitro Techniquesen
dc.subject.otherMembrane Potentials.drug effects.geneticsen
dc.subject.otherPatch-Clamp Techniquesen
dc.subject.otherRats, Sprague-Dawleyen
dc.subject.otherRats, Wistaren
dc.subject.otherReceptors, N-Methyl-D-Aspartate.genetics.metabolismen
dc.subject.otherSecondary Preventionen
dc.subject.otherTaurine.analogs & derivatives.chemistry.pharmacology.therapeutic useen
dc.subject.otherXenopus laevisen
dc.titleAcamprosate produces its anti-relapse effects via calcium.en
dc.typeJournal Articleen
dc.identifier.journaltitleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacologyen
dc.identifier.affiliationFlorey Institute of Neuroscience & Mental Health, University of Melbourne, Melbourne, Australiaen
dc.identifier.affiliationXenoPort, Inc., Santa Clara, CA, USAen
dc.identifier.affiliationInstitute of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.en
dc.identifier.affiliationDepartment of Addictive Behavior and Addiction Medicine, Central Institute for Mental Health, Mannheim, Germany.en
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
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