Acamprosate inhibits Ca²⁺ influx mediated by NMDA receptors and voltage-sensitive Ca²⁺ channels in cultured rat mesencephalic neurones

Abstract

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 ω-conotoxin (ω-CTX) MVIIC, a blocker of voltage-dependent Ca²⁺ channels (VDCCs). Acamprosate (100 µM and 300 µM) significantly attenuated the response induced by NMDA as well as that induced by K⁺ in a concentration-dependent manner. Concurrent application of ω-CTX MVIIC and acamprosate impaired the K⁺-induced increase in [Ca²⁺]_i to the same extent as ω-CTX MVIIC alone. The present data suggest that acamprosate inhibits Ca²⁺ influx through both NMDA receptors and VDCCs.