PMID: 9443926Jan 28, 1998Paper

Nefiracetam modulates acetylcholine receptor currents via two different signal transduction pathways

Molecular Pharmacology
T NishizakiM Yoshii

Abstract

Nootropic agents are proposed to serve as cognition enhancers. The underlying mechanism, however, is largely unknown. The present study was conducted to assess the intracellular signal transduction pathways mediated by the nootropic nefiracetam in the native and mutant Torpedo californica nicotinic acetylcholine (ACh) receptors expressed in Xenopus laevis oocytes. Nefiracetam induced a short-term depression of ACh-evoked currents at submicromolar concentrations (0.01-0.1 microM) and a long-term enhancement of the currents at micromolar concentrations (1-10 microM). The depression was caused by activation of pertussis toxin-sensitive, G protein-regulated, cAMP-dependent protein kinase (PKA) with subsequent phosphorylation of the ACh receptors; in contrast, the enhancement was caused by activation of Ca(2+)-dependent protein kinase C (PKC) and the ensuing PKC phosphorylation of the receptors. Therefore, nefiracetam interacts with PKA and PKC pathways, which may explain a cellular mechanism for the action of cognition-enhancing agents.

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Citations

Jun 13, 2000·Alzheimer Disease and Associated Disorders·M YoshiiT Shiotani
Mar 2, 1999·British Journal of Pharmacology·K YamadaT Nabeshima
Oct 24, 2006·Journal of Neurochemistry·Cornelis J Van der SchyfMoussa B H Youdim
Sep 6, 2005·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Hiroyuki MizoguchiToshitaka Nabeshima
Aug 9, 2011·Journal of Pharmacological Sciences·Shigeki Moriguchi
Aug 9, 2019·Psychopharmacology·Charlotte R Flavell, Jonathan L C Lee
Jan 14, 2004·The Journal of Pharmacology and Experimental Therapeutics·Mutsumi UedaHiroshi Ueda
Aug 18, 2005·Toxicologic Pathology·Yoshimi TsuchiyaKazuo T Suzuki
Jun 15, 2010·Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie·Ricardo E JorgeRobert G Robinson
Sep 23, 2016·Evidence-based Complementary and Alternative Medicine : ECAM·Noor Azuin SulimanRusliza Basir
Nov 16, 2004·Annals of the New York Academy of Sciences·Yijin YanToshitaka Nabeshima
Nov 2, 2004·Biological & Pharmaceutical Bulletin·Toshio NarahashiJay Zeus Yeh
Jan 18, 2008·Journal of Medicinal Chemistry·Ramin FaghihClark A Briggs

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