Deramciclane inhibits N-methyl-D-aspartate receptor function.
Effects of the novel anxiolytic drug deramciclane on excitatory amino acid release and transmembrane Ca(2+) ion flux processes were compared in rat cerebrocortical homogenates containing resealed plasmalemma fragments and nerve endings. Deramciclane (10 microM) significantly inhibited [(3)H]D-aspartate release and transmembrane Ca(2+) flux to N-methyl-D-aspartate in the absence of Mg(2+). By contrast, inhibition of [(3)H]D-aspartate release and transmembrane Ca(2+) flux evoked by 0.1 mM (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate in the presence of Mg(2+) and 10 microM cyclothiazide by 10 microM deramciclane was not significant. In the presence of N-methyl-D-aspartate receptor antagonists, deramciclane (10 microM) did not inhibit [(3)H]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.
Kovács
I
I
Department of Neurochemistry, Chemical Institute, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
Szárics
E
E
Skuban
N
N
Kardos
J
J
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001224:Aspartic Acid / Q000037:antagonists & inhibitors; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D001892:Camphanes / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D001892:Camphanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D001569:Benzodiazepines; D001224:Aspartic Acid; D016291:Dizocilpine Maleate; D015761:4-Aminopyridine; C085266:talampanel; D008274:Magnesium; C060555:deramciclane; D002118:Calcium