Deramciclane inhibits N-methyl-D-aspartate receptor function

Effects of the novel anxiolytic drug deramciclane on excitatory amino acid release and transmembrane Ca2+ ion flux processes were compared in rat cerebrocortical homogenates containing resealed plasmalemma fragments and nerve endings. Deramciclane (10 mu M) significantly inhibited [H-3]D-aspartate release and transmembrane Ca2+ flux to N-methyl-D-aspartate in the absence of Mg2+. By contrast, inhibition of [H-3]D-aspartate release and transmembrane Ca2+ flux evoked by 0.1 mM (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate in the presence of Mg2+ and 10 mu M cyclothiazide by 10 mu M deramciclane was not significant. In the presence of N-methyl-D-aspartate receptor antagonists, deramciclane (10 mu M) did not inhibit [H-3]D-aspartate release to N-methyl-D-aspartate, These results suggest an involvement of the inhibition of a presynaptic N-methyl-D-aspartate receptor in the anxiolytic properties of deramciclane. (C) 2000 Elsevier Science Inc.