1-BCP, a memory-enhancing agent, selectively potentiates AMPA-induced [3H]norepinephrine release in rat hippocampal slices

Neuropharmacology. 1995 Feb;34(2):141-7. doi: 10.1016/0028-3908(94)00128-f.


It is now clear that the AMPA subtype of ionotropic glutamate receptors (iGluRs) undergoes a rapid desensitization in response to activation by AMPA receptor agonists. This desensitization is inhibited by compounds such as aniracetam and cyclothiazide, which act at a distinct site on the AMPA receptor complex. In particular, cyclothiazide greatly potentiates AMPA receptor-mediated depolarizing responses in the hippocampus. We have recently shown cyclothiazide also increases AMPA-induced release of [3H]norepinephrine ([3H]NE). More, recently, a benzamide compound, 1-(1,3-benzodioxol-5-ylcarbonyl)-piperidine (1-BCP), has been reported to enhance AMPA-induced currents and to facilitate memory retention in rats in a number of memory tasks. In this study, the effects of 1-BCP on excitatory amino acid agonist-induced [3H]NE release in rat hippocampal slices were determined. We report that 1-BCP, like cyclothiazide, selectively potentiates AMPA-induced [3H]NE release. However, cyclothiazide was more potent and efficacious than 1-BCP. Nevertheless, these data suggest a role for AMPA receptor-mediated enhancement of norepinephrine release as a mechanism of action for nootropic compounds such as 1-BCP.

MeSH terms

  • Animals
  • Benzothiadiazines / pharmacology*
  • Dioxoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology
  • Hippocampus / drug effects
  • Kainic Acid / pharmacology
  • Male
  • Memory
  • N-Methylaspartate / pharmacology
  • Norepinephrine / metabolism*
  • Piperidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / drug effects*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Benzothiadiazines
  • Dioxoles
  • Excitatory Amino Acid Agonists
  • Piperidines
  • Receptors, AMPA
  • 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • cyclothiazide
  • Kainic Acid
  • Norepinephrine