Hypnotic drugs such as benzodiazepines are associated with memory impairment, dementia, depression, and cause dependency and withdrawal phenomena in chronic usage ( 3). Although the importance of having a good sleep is well-established, most people suffering from low-quality sleep do not look for medication since many hypnotics and sedatives have side effects. Sleep problems, including difficulty in falling asleep, decreased sleep duration, and inconsistent sleep/wake patterns affect 56% of people in the United States, 31% in Western Europe, 23% in Japan ( 1), and are a significant cause of morbidity and mortality ( 2). Sleep disturbances encompass numerous disorders which have detrimental impacts on the quality of life. As a result, our data indicate that Mg- L-theanine compounds potentiate the effect of L-theanine on sleep by boosting slow-brain waves, regulating brain electrical activity, and increasing neurotransmitter and GABA receptor levels. In accordance with these results, Mg complexes improved the sleep latency and duration even after caffeine administration. Protein expression analyses also showed that Mg- L-theanine complexes decrease inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) levels significantly. Besides increased dopamine, serotonin, and melatonin decreased MDA and increased antioxidant enzyme levels were also observed particularly with Mg-complexes. We herein showed that L-theanine, particularly its various complexes with magnesium increases the expression of GABAergic, serotonergic, and glutamatergic receptors, which were associated with decreased ECoG frequency, increased amplitude, and enhanced delta wave powers. Furthermore, we evaluated the sleep latency and duration in the pentobarbital induced sleep model. Using the caffeine-induced brain electrical activity model, here we investigated the potency of L-theanine and two novel Mg- L-theanine compounds with different magnesium concentrations on electrocorticography (ECoG) patterns, GABAergic and serotonergic receptor expressions, dopamine, serotonin, and melatonin levels. On the other hand, Mg 2+, a natural NMDA antagonist and GABA agonist, has a critical role in sleep regulation. L-Theanine is commonly used to improve sleep quality through inhibitory neurotransmitters.
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