N-Acetyl-5-hydroxytryptamine (O-Demethylmelatonin) , also known as Normelatonin, is the immediate precursor of melatonin. It is produced from serotonin by the enzyme aralkylamine N-acetyltransferase and is converted to melatonin by acetylserotonin O-methyltransferase. It can potently activate TrkB receptor.

N-acetylserotonin activates TrkB receptor in a circadian rhythm. N-Acetyl-5-hydroxytryptamine swiftly activates TrkB in a circadian manner and exhibits antidepressant effect in a TrkB-dependent manner. N-Acetyl-5-hydroxytryptamine rapidly activates TrkB, but not TrkA or TrkC, in a neurotrophin- and MT3 receptor-independent manner[1].

To investigate the potential of N-Acetyl-5-hydroxytryptamine (NAS) to activate TrkB in vivo, researchers utilized TrkB F616A knockin mice, which have been demonstrated to exhibit selective inhibition of TrkB F616A activation by 1NMPP1, a derivative of the kinase inhibitor PP1, resulting in TrkB-null phenotypes. The study aimed to determine if NAS could replicate the effects of BDNF. Cortical neurons from TrkB F616A knockin mice were prepared for this purpose. Supporting previous findings, the study showed that NAS and BDNF-induced TrkB phosphorylation were specifically diminished by 1NMPP1, unlike by K252a, while serotonin or melatonin had no impact. These results suggest that NAS significantly induces tyrosine phosphorylation and activation of both wild-type TrkB and TrkB F616A[1].