Melatonin

Category: sleep

Pharmacological Mechanism

MT1/MT2 agonist; entrains the circadian clock bmal1 per cry circadian rhythm.

Half-Life (t½)

PO: 0.7h, SL: 0.5h

Dosing Guidelines

PO: Typical 0.5 (Range: 0.3–5)
SL: Typical 0.5 (Range: 0.3–3)

Target Organ Systems

nervous
endocrine
digestive

Notes

Lower doses (0.3mg) often outperform high doses for sleep onset. PO has heavy first-pass; SL bypasses much of it. MT1 Ki ~80 pM = 0.0000186 mg/L, MT2 Ki ~270 pM = 0.0000626 mg/L (melatonin MW 232 g/mol). Therapeutic plasma at 0.5 mg PO peaks ~80-100 pg/mL = ~1e-4 mg/L, well above both receptor EC50s — both are saturated within minutes of dosing.

Pathways It Modulates

AMPK energy sensor (activator) — AMPK (chronic, anti-inflammatory)
Brown adipose thermogenesis (activator) — BAT mass + activity (circadian-linked)
Circadian clock (activator) — MT1 / MT2 (clock-resetting)
GSH / GSSG redox cycle (activator) — direct radical scavenger + GPx induction in CNS
Kynurenine pathway (inhibitor) — IDO1 expression (anti-inflammatory)
Melatonin MT1/MT2 dose-response + REM rebound (activator) — MT1 + MT2 receptors
Neuroinflammation (inhibitor) — microglial NF-κB; oxidative stress; circadian-driven anti-inflammatory
Parkinson disease (inhibitor) — oxidative + nitrosative stress; circadian + REM-disorder co-management
TLR (Toll-like receptor) innate signaling (inhibitor) — TLR4 / NF-κB (anti-inflammatory)
Tryptophan → serotonin → melatonin (substrate) — endpoint

Chemical Identifiers

PubChem CID: 896
Formula: C13H16N2O2
Molecular weight: 232.28 g/mol
InChIKey: DRLFMBDRBRZALE-UHFFFAOYSA-N
SMILES: CC(=O)NCCC1=CNC2=C1C=C(C=C2)OC