It may contribute to multifactorial genetic diseases such as altered behavior in sleep/wake cycle[2] and research is on-going with the aim of developing drugs that regulate AANAT function.

Melatonin is essential for seasonal reproduction, modulates the function of the circadian clock in the suprachiasmatic nucleus, and influences activity and sleep.

AANAT catalyzes the transfer of the acetyl group of Acetyl-CoA to the primary amine of serotonin, thereby producing CoA and N-acetylserotonin.

In humans, other endogenous substrates of the enzyme include specific trace amine neuromodulators, namely phenethylamine, tyramine, and tryptamine, in turn forming N-acetylphenethylamine, N-acetyltyramine, and N-acetyltryptamine.

In other species, cyclic AMP plays an important part in inhibition of proteolytic degradation of AANAT, elevating protein levels at night.

[15] Exposure to light induces signals to travel from retinal cells, ultimately causing a drop in norepinephrine stimulation of the pineal gland.

This, in turn, leads to a signaling cascade, resulting in Protein Kinase A phosphorylation of two key Ser and Thr residues of serotonin N-acetyltransferase.

[17] Inhibition of the acetyl-CoA-binding to the catalytic site through the formation and cleavage of intramolecular disulfide bonds has been suggested to be a mechanism of regulation.

[18] Inhibitors of AANAT may eventually lead to development of a drug that would be useful in circadian biology research and in the treatment of sleep and mood disorders.

Molecular modeling and structure-activity relationship studies made it possible to pinpoint the amino acid residue of the pentapeptide inhibitor S 34461 that interacts with the cosubstrate-binding site.

[24] It is suggested that AANAT catalyzes the transfer of an acetyl group from acetyl-CoA to serotonin, with the involvement of an intermediate ternary complex, to produce N-acetylserotonin.

Based on this mechanism, it might be expected that a bisubstrate analog inhibitor, derived from the tethering of indole and CoASH parts, could potentially mimic the ternary complex and exert strong inhibition of AANAT.

[25] The first bisubstrate analog (1), which links tryptamine and CoA via an acetyl bridge, was synthesized by Khalil and Cole, and shown to be a very potent and specific AANAT inhibitor.

AANAT catalyzes reaction between N-bromoacetyltryptamine (BAT) and reduced CoA, resulting a tight-binding bisubstrate analog inhibitor.

One compound class which containing a rhodanine scaffold has shown low micromolar competitive inhibition against acetyl-CoA and proved to be effective in blocking melatonin production in pineal cells.