1-BCP, a memory-enhancing agent, selectively potentiates AMPA-induced [3H]norepinephrine release in rat hippocampal slices.
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.
Desai
M A
MA
Central Nervous System Research, Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Valli
M J
MJ
Monn
J A
JA
Schoepp
D D
DD
D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008568:Memory; D016202:N-Methylaspartate / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D001581:Benzothiadiazines; D004149:Dioxoles; D018690:Excitatory Amino Acid Agonists; D010880:Piperidines; D018091:Receptors, AMPA; C085415:1-(1,3-benzodioxol-5-ylcarbonyl)piperidine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C004639:cyclothiazide; D007608:Kainic Acid; D009638:Norepinephrine