Mechanism of action
L-theanine (N-ethyl-L-glutamine) or theanine is a major amino acid uniquely found in green tea. L-theanine has been historically reported as a relaxing agent, prompting scientific research on its pharmacology. Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors. In addition has been shown to exert neuroprotective effects in animal models possibly through its antagonistic effects on group 1 metabotrophic glutamate receptors. Behavioural studies in animals suggest improvement in learning and memory. Overall, L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent and warrants further investigation in animals and humans.
In an investigation of the mechanisms of the neuroprotective effects of theanine (gamma-glutamylethylamide) in brain ischemia, inhibition by theanine of the binding of [(3)H](RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [(3)H]kainate, and [(3)H](E)-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1-H-indole-2-carboxylic acid (MDL 105,519) to glutamate receptors was studied in terms of its possible inhibiting effects on the three receptor subtypes (AMPA, kainate, and NMDA glycine), with rat cortical neurons. Theanine bound the three receptors, but its IC50 of theanine was 80- to 30,000-fold less than that of L-glutamic acid.
In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a conditioned place preference (CPP) model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine (DHbetaE). Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly inhibited nicotine-induced tyrosine hydroxylase (TH) expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the a(4), beta(2) and a(7) nicotine acetylcholine receptor (nAChR) subunits induced by nicotine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of tobacco addiction.
L-theanine, previously shown to penetrate the blood-brain barrier through the leucine-preferring transport system, has been demonstrated to produce significant increases in serotonin and/or dopamine concentrations in the brain principally in the striatum, hypothalamus and hippocampus.
For more Mechanism of Action (Complete) data for Theanine (9 total), please visit the HSDB record page.
Pharmacokinetics
Absorption
From animal studies, it appears that L-theanine is absorbed from the small intestine via a sodium-coupled active transport process and appears to cross the blood-brain barrier. It has been found in the rat studies that the D-enantiomer of theanine may decrease the absorption of L-theanine.
Metabolism
In medium containing theanine with glutaminase in vitro, glutamate gradually generated, showing that glutaminase reacted with theanine. Furthermore, the generation of glutamate increased by reaction of theanine and gamma-glutamyltranspeptidase (gamma-GTP), showed that gamma-GTP converted theanine to glutamate. It is expected that theanine metabolism occurred by hydrolysis and rearrangement reaction by gamma-GTP in the liver. Namely, it is suggested that the metabolism of theanine mediated by glutaminase and gamma-GTP and the increase of glutamate mediated GSH is important for theanine-induced action.
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.