Inhibition of [3H]D-aspartate release by deramciclane

Ilona Kovács, Nina Skuban, G. Nyitrai, J. Kardos

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The effects of the 5-HT(2C) receptor inverse agonist deramciclane on the γ-aminobutyric acid (GABA) uptake and excitatory amino acid release processes were compared in rat cerebrocortical homogenates containing resealed plasmalemma fragments and nerve endings. Deramciclane non- competitively inhibited the uptake of [3H]GABA with a K(i) value of 13.7±0.5 μM and partially displaced specifically bound [3H](R,S)-N-[4,4- bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid ([3H]NNC-328) with high affinity (IC50=2.0±0.7 nM). Depolarization by 4-aminopyridine or by 4- aminopyridine with (S)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionate [(S)-AMPA] induced the release of [3H]D-aspartate. Deramciclane (10 μM) partially (~50%) inhibited the release of [3H]D-aspartate without affecting [3H]D-aspartate uptake. These results suggest a role for presynaptic inhibition of excitatory amino acid release and GABA uptake in the anxiolytic properties of deramciclane.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalEuropean Journal of Pharmacology
Volume381
Issue number2-3
DOIs
Publication statusPublished - Sep 24 1999

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D-Aspartic Acid
gamma-Aminobutyric Acid
4-Aminopyridine
Excitatory Amino Acids
Receptor, Serotonin, 5-HT2C
Aminobutyrates
Isoxazoles
Nerve Endings
Anti-Anxiety Agents
Propionates
Inhibitory Concentration 50
deramciclane

Keywords

  • (Rat)
  • [H]D-aspartic acid, release, uptake
  • [H]GABA ([H]γ- aminobutyric acid), uptake
  • [H]NNC-328 {[H](R,S)-N-[4,4- bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid} binding
  • Cerebrocortical homogenate
  • Deramciclane
  • Quench flow

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Inhibition of [3H]D-aspartate release by deramciclane. / Kovács, Ilona; Skuban, Nina; Nyitrai, G.; Kardos, J.

In: European Journal of Pharmacology, Vol. 381, No. 2-3, 24.09.1999, p. 121-127.

Research output: Contribution to journalArticle

Kovács, Ilona ; Skuban, Nina ; Nyitrai, G. ; Kardos, J. / Inhibition of [3H]D-aspartate release by deramciclane. In: European Journal of Pharmacology. 1999 ; Vol. 381, No. 2-3. pp. 121-127.
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