Characterization of l -Theanine Excitatory Actions on Hippocampal Neurons: Toward the Generation of Novel N -Methyl- d -aspartate Receptor Modulators Based on Its Backbone

authors

• Sebih Fatiha
• Rousset Matthieu
• Bellahouel Salima
• Rolland Marc
• de Jesus Ferreira Marie Celeste
• Guiramand Janique
• Cohen-Solal Catherine
• Barbanel Gérard
• Cens Thierry
• Abouazza Mohammed
• Tassou Adrien
• Gratuze Maud
• Meusnier Céline
• Charnet Pierre
• Vignes Michel
• Rolland Valérie

keywords

• L-γ-N-propyl-glutamine
• L-Theanine
• Microwave-assisted organic synthesis MAOS
• NMDA receptors
• Hippocampal neurons
• Intracellular Ca 2+ homeostasis
• Expression
• Xenopus oocytes
• GluN2B
• GluN2A

abstract

L-Theanine (or L-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has received much attention because of its pleiotropic physiological and pharmacological activities leading to health benefits in humans, especially. We describe here a new, easy, efficient, and environmentally friendly chemical synthesis of L-theanine and L-γ-N-propyl-Gln and their corresponding D-isomers. L-Theanine, and its derivatives obtained so far, exhibited partial coagonistic action at N-methyl-D-aspartate (NMDA) receptors, with no detectable agonist effect at other glutamate receptors, on cultured hippocampal neurons. This activity was retained on NMDA receptors expressed in Xenopus oocytes. In addition, both GluN2A and GluN2B containing NMDA receptors were equally modulated by L-theanine. The stereochemical change from L-theanine to D-theanine along with the substitution of the ethyl for a propyl moiety in the γ-N position of Land D-theanine significantly enhanced the biological efficacy, as measured on cultured hippocampal neurons. L-Theanine structure thus represents an interesting backbone to develop novel NMDA receptor modulators.

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