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 chronic 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 dynamic proton magnetic resonance spectroscopy (MRS) measurements localized in brain tissue in vivo. Recordings were performed after intravenous administration of acamprosate or placebo to eight healthy male volunteers participating in a double-blind, randomized, cross-over, placebo-controlled study. The data were acquired using a spin-echo volume selective localized spectroscopy scheme on a 3-T whole body MRS system. Spectra obtained at baseline and at 20-min time intervals after the beginning of drug infusion were analyzed on the basis of five non-overlapping spectral integration regions. In the acamprosate-treated group, the median integral values in the regions for which N-acetylaspartate and 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 microdialysis glutamate measurements in vivo obtained from alcoholized rats treated with acamprosate (Part 1 of this study). This study is to our knowledge the first one describing a central effect of acamprosate in humans by MRS.
Bolo
N
N
FORENAP, Unité de Résonance Magnétique, Centre Hospitalier, Rouffach, France. nbolo@forenap.asso.fr
Nédélec
J F
JF
Muzet
M
M
De Witte
P
P
Dahchour
A
A
Durbin
P
P
Macher
J P
JP
D000077443:Acamprosate; D000328:Adult; D000427:Alcohol Deterrents / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D018592:Cross-Over Studies; D004151:Dipeptides / Q000378:metabolism; D004311:Double-Blind Method; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000427:Alcohol Deterrents; D004151:Dipeptides; D010725:Phosphocreatine; D005973:Glutamine; D013654:Taurine; C027172:isospaglumic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D000077443:Acamprosate