Neurotoxic effect of acamprosate, n-acetyl-homotaurine, in cultured neurons

Abstract

Acamprosate (AC), N-acetyl-homotaurine, has recently been introduced for treating alcohol craving and reducing relapses in weaned alcoholics. AC may exert its action through the taurine system rather than the glutamatergic or GABAergic system. This conclusion is based on the observations that AC strongly inhibits the binding of taurine to taurine receptors while it has little effect on the binding of glutamate to glutamate receptors or muscimol to GABA(A) receptors. In addition, AC was found to be neurotoxic, at least in neuronal cultures, triggering neuronal damage at 1 mM. The underlying mechanism of AC-induced neuronal injury appears to be due to its action in increasing the intracellular calcium level, [Ca2+](i). Both AC-induced neurotoxicity and elevation of [Ca2+](i) can be prevented by taurine suggesting that AC may exert its effect through its antagonistic interaction with taurine receptors.