Drug information of Melatonin


In mammals, melatonin is produced by the pineal gland. The secretion of melatonin increases in darkness and decreases during exposure to light, thereby regulating the circadian rhythms of several biological functions, including the sleep-wake cycle.

Mechanism of effect

The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. MT1 receptors are expressed in many regions of the central nervous system (CNS):

suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantianigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens.

MT1 is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT2 receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes. The binding of melatonin to melatonin receptors activates a few signaling pathways. Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylatecylcase and the inhibition of a cAMPsignal transduction pathway. Melatonin not only inhibits adenylatecyclase, but it also activates phosphilpase C.

 This potentiates the release of arachidonate. By binding to melatonin receptors 1 and 2, the downstream signallling cascades have various effects in the body.  MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell.

The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP. As well it hinders guanylylcyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell.


In particular, melatonin regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature. Melatonin is also implicated in the regulation of mood, learning and memory, immune activity, dreaming, fertility and reproduction. Melatonin is also an effective antioxidant.

Drug indications




3-5 mg PO qHS

Difficulty falling asleep

  • 5 mg PO 3-4 hour before sleep period x 4 weeks

Jet Lag

0.5-5 mg PO HS


  • Preflight, early evening dose followed by HS dosing x 4days


  • Treat HS x 4days when in new time zone


Age <20 years old, depression, hypertension, impaired liver function, seizure disorder

Points of recommendation

  • Avoid driving or operating machinery for at least 4 hours after taking melatonin.
  • Avoid using this medication with other prescription medications, over-the-counter drugs, or dietary supplements without asking your doctor, pharmacist or other healthcare provider.
  • Avoid alcohol while taking this medication.
  • Avoid coffee, tea, cola, energy drinks, or other products that contain caffeine, as it may counteract the effects of the melatonin.

Pregnancy level

Not assigned

Related drugs

Zolpidem , Ramelteon

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