The neuropharmacology of L-theanine(N-ethyl-L-glutamine): A possible neuroprotective and cognitive enhancing agent

Behavioural Neuroscience Laboratory, Department of Physiology, Monash Center for Brain and Behaviour, Monash University, Australia.
Journal of Herbal Pharmacotherapy 02/2006; 6(2):21-30. DOI: 10.1080/J157v06n02_02
Source: PubMed

ABSTRACT 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.

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    • "). Remarkably, EGCG decreases Aβ levels and plaques in mice, reduced Aβ mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice (Lee et al. 2009; Rezai-Zadeh et al. 2005, 2008), as well as prevents Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca 2+ influx and ROS production (He et al. 2011). In addition to tea catechins, theanine, which is an amino acid uniquely found in tea leaf, may also possess neuroprotective effect (Nathan et al. 2006), probably by its antagonistic effect on ionotropic glutamate receptor subtypes, such as NMDARs (Kakuda 2011). Moreover , the beneficial effects of caffeine on stress-induced memory disturbance are mimicked by antagonists of adenosine A2a receptors, likely mediated by its ability to control glutamatergic transmission, especially NMDAR-dependent plasticity (Cunha and Agostinho 2010). "
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    ABSTRACT: It has been proposed that green tea extract may have a beneficial impact on cognitive functioning, suggesting promising clinical implications. However, the neural mechanisms underlying this putative cognitive enhancing effect of green tea extract still remain unknown. This study investigates whether the intake of green tea extract modulates effective brain connectivity during working memory processing and whether connectivity parameters are related to task performance. Using a double-blind, counterbalanced, within-subject design, 12 healthy volunteers received a milk whey-based soft drink containing 27.5 g of green tea extract or a milk whey-based soft drink without green tea as control substance while undergoing functional magnetic resonance imaging. Working memory effect on effective connectivity between frontal and parietal brain regions was evaluated using dynamic causal modeling. Green tea extract increased the working memory induced modulation of connectivity from the right superior parietal lobule to the middle frontal gyrus. Notably, the magnitude of green tea induced increase in parieto-frontal connectivity positively correlated with improvement in task performance. Our findings provide first evidence for the putative beneficial effect of green tea on cognitive functioning, in particular, on working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto-frontal brain connections. Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in psychiatric disorders such as dementia.
    Psychopharmacology 03/2014; 231(19). DOI:10.1007/s00213-014-3526-1 · 3.99 Impact Factor
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    • "L-Theanine was originally found in green tea and has historically been recognized as a relaxing agent (de Mejia et al. 2009; Nathan et al. 2006). Besides its similar chemical structure to glutamate, L-theanine shows micromolar affinities for kainate, α-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA), and N-methyl D-aspartate (NMDA) glutamate receptors (Kakuda et al. 2002). "
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    ABSTRACT: l-Theanine (N-ethyl-l-glutamine) is an amino acid uniquely found in green tea. Growing evidence has suggested the possible effects of l-theanine on cognition. Previously, we found that l-theanine attenuates MK-801-induced deficit in prepulse inhibition (PPI) in mice. In this study, we examined the effect of l-theanine in increasing the PPI in healthy humans. The subjects were 14 healthy adults who underwent PPI testing as a measure of sensorimotor gating 90 min after an oral intake of l-theanine (0, 200, 400, or 600 mg). PPI tests were done by examiners who were blind to the dose. The administration of 200 mg of l-theanine and that of 400 mg, but not 600 mg, significantly increased the % PPI compared to the baseline (0 mg). There was no significant relation between the dose of l-theanine and the startle magnitude or the habituation of startle response. The plasma concentrations of l-theanine correlated with the dose of l-theanine. The observed effect with 200-400 mg of l-theanine on PPI suggested that l-theanine at a particular dose range increases sensorimotor gating in humans.
    Psychiatry and Clinical Neurosciences 12/2013; 68(5). DOI:10.1111/pcn.12134 · 1.62 Impact Factor
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    • "L-theanine (γ-glutamylet-hylamide) is a major component accounting for 40~60% of the total amino acid in green tea (Juneja et al, 1999). Since it is a neurotransmitter with neuroprotective effects, there are many reports about its pharmacodynamics in the neuroscientific field (Cho et al, 2008; Kimura et al, 2007; Nathan et al, 2006; Park et al, 2011). In the immunological filed, administration of L-theanine together with L-cystine has been shown to induce a significant increase of endogenous antioxidant levels in the liver, and antigen-specific IgG antibody and T helper cytokine in serum of animal models (Bukowski and Percival, 2008; Kurihara et al, 2007). "
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    ABSTRACT: L-theanine was examined for its effects on the generation of superoxide anion, lysozyme and anti-protease in the plasma of catfish (Silurus asotus) by a single intraperitoneal injection with five different concentrations (0, 3, 6, 9 and 12 mg/kg). When compared with the mock-injected group (0 mg/kg), both groups injected with 6 and 9 mg/kg were significantly enhanced in levels of superoxide anion in leukocytes, lysozyme and anti-protease in plasma. Based on the results, L-theanine is thought to function as an immunostimulant and/or immunomodulator on non-specific immune responses in catfish.
    12/2012; 35(4). DOI:10.7853/kjvs.2012.35.4.347
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