Acamprosate inhibits Ca2+ influx mediated by NMDA receptors and voltage-sensitive Ca2+ channels in cultured rat mesencephalic neurones.
Acamprosate has recently been introduced in relapse prophylaxis in weaned alcoholics. Using fura-2 microfluorimetry, the present study investigates whether acamprosate affects N-methyl-D-aspartate (NMDA) or K+-induced changes in free intracellular Ca2+ concentration ([Ca2+]i) in rat cultured mesencephalic neurones. Both application of NMDA (plus glycine) and elevation of extracellular K+ induced rapid increases in [Ca2+]i which respectively were insensitive and sensitive to omega-conotoxin (omega-CTX) MVIIC, a blocker of voltage-dependent Ca2+ channels (VDCCs). Acamprosate (100 microM and 300 microM) significantly attenuated the response induced by NMDA as well as that induced by K+ in a concentration-dependent manner. Concurrent application of omega-CTX MVIIC and acamprosate impaired the K+-induced increase in [Ca2+]i to the same extent as omega-CTX MVIIC alone. The present data suggest that acamprosate inhibits Ca2+ influx through both NMDA receptors and VDCCs.
Allgaier
C
C
Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, Germany. allgc@medizin.uni-leipzig.de
Franke
H
H
Sobottka
H
H
Scheibler
P
P
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020960:omega-Conotoxins / Q000494:pharmacology
D000427:Alcohol Deterrents; D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D013654:Taurine; D000077443:Acamprosate; D002118:Calcium