CENTRAL EFFECTS OF ACAMPROSATE - PART-2 - ACAMPROSATE MODIFIES THE BRAIN IN-VIVO PROTON MAGNETIC-RESONANCE SPECTRUM IN HEALTHY-YOUNG MALE-VOLUNTEERS

Although acamprosate is a drug which is successfully used for therapy in maintaining alcohol abstinence following alcohol withdrawal in chro nic alcoholism, little is understood about its mechanism of action in the central nervous system. Our objective was to assess the effects of acamprosate on the central nervous system in healthy subjects by dyna mic proton magnetic resonance spectroscopy (MRS) measurements localize d in brain tissue in vivo. Recordings were performed after intravenous administration of acamprosate or placebo to eight healthy male volunt eers participating in a double-blind, randomized, cross-over, placebo- controlled study. The data were acquired using a spin-echo volume sele ctive localized spectroscopy scheme on a 3-T whole body MRS system. Sp ectra obtained at baseline and at 20-min time intervals after the begi nning of drug infusion were analyzed on the basis of five non-overlapp ing spectral integration regions. In the acamprosate-treated group, th e median integral values in the regions for which N-acetylaspartate an d glutamate are the main signal contributors showed decreases relative to placebo 20 min after the infusion began. Results suggest a central glutamatergic effect of acamprosate consistent with cerebral microdia lysis glutamate measurements in vivo obtained from alcoholized rats tr eated with acamprosate (Part 1 of this study). This study is to our kn owledge the first one describing a central effect of acamprosate in hu mans by MRS. (C) 1998 Elsevier Science Ireland Ltd. All rights reserve d.