[3H]aniracetam binds to specific recognition sites in brain membranes

J Neurochem. 1995 Aug;65(2):912-8. doi: 10.1046/j.1471-4159.1995.65020912.x.


[3H]Aniracetam bound to specific and saturable recognition sites in membranes prepared from discrete regions of rat brain. In crude membrane preparation from rat cerebral cortex, specific binding was Na+ independent, was still largely detectable at low temperature (4 degrees C), and underwent rapid dissociation. Scatchard analysis of [3H]aniracetam binding revealed a single population of sites with an apparent KD value of approximately 70 nM and a maximal density of 3.5 pmol/mg of protein. Specifically bound [3H]aniracetam was not displaced by various metabolites of aniracetam, nor by other pyrrolidinone-containing nootropic drugs such as piracetam or oxiracetam. Subcellular distribution studies showed that a high percentage of specific [3H]aniracetam binding was present in purified synaptosomes or mitochondria, whereas specific binding was low in the myelin fraction. The possibility that at least some [3H]aniracetam binding sites are associated with glutamate receptors is supported by the evidence that specific binding was abolished when membranes were preincubated at 37 degrees C under fast shaking (a procedure that substantially reduced the amount of glutamate trapped in the membranes) and could be restored after addition of either glutamate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) but not kainate. The action of AMPA was antagonized by DNQX, which also reduced specific [3H]aniracetam binding in unwashed membranes. High levels of [3H]aniracetam binding were detected in hippocampal, cortical, or cerebellar membranes, which contain a high density of excitatory amino acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Anti-Anxiety Agents*
  • Benzodiazepines / pharmacology
  • Benzothiadiazines / pharmacology
  • Binding Sites
  • Brain / metabolism*
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Glutamic Acid / pharmacology
  • Male
  • Membranes / metabolism
  • Phorbol 12,13-Dibutyrate / metabolism
  • Pyrrolidinones / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Tritium


  • Anti-Anxiety Agents
  • Benzothiadiazines
  • Pyrrolidinones
  • Tritium
  • GYKI 52466
  • Benzodiazepines
  • Phorbol 12,13-Dibutyrate
  • Glutamic Acid
  • aniracetam
  • cyclothiazide