GlycinevsMelatonin

Glycine acts as an inhibitory neurotransmitter by binding to strychnine-sensitive glycine receptors (GlyR) in the brainstem, spinal cord, and retina, hyperpolarizing neurons via chloride influx. It also serves as a mandatory co-agonist at the glycine-binding site (NR1 subunit) of NMDA glutamate receptors — without glycine binding, NMDA receptors cannot open their ion channel even when glutamate is present. This dual role means glycine both calms neural activity (sleep, anti-anxiety via GlyR) and supports excitatory learning processes (NMDA-dependent LTP and memory consolidation). Glycine lowers core body temperature at night by promoting peripheral vasodilation through nitric oxide, which improves sleep onset. It is a precursor for glutathione synthesis and modulates the glycinergic system in the suprachiasmatic nucleus.

Melatonin binds to G-protein-coupled MT1 and MT2 receptors, which are densely expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus—the brain's master circadian pacemaker. MT1 activation couples to Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP, which suppresses SCN neuronal firing and promotes sleepiness. MT2 activation modulates cGMP signaling and phase-shifts the circadian rhythm (useful for jet lag and shift work). Melatonin also has direct antioxidant properties, scavenging hydroxyl and peroxyl radicals in mitochondria and upregulating antioxidant enzymes like glutathione peroxidase. It supports immune function through modulation of T-cell cytokine production and may act at MT3 (quinone reductase 2) binding sites. Low doses are often more effective because they mimic physiological nighttime levels.