Molecular formula C
12H 14N 2O 2
Molar mass 218.252 g/mol
Density 1.268 g/mL
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Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
( N-Acetylserotonin NAS), also known as normelatonin, is a naturally occurring chemical intermediate in the endogenous production of melatonin from serotonin. 1 It is produced from serotonin by the 2 enzyme aralkylamine (AANAT) and is converted to melatonin by N-acetyltransferase acetylserotonin (ASMT). Like melatonin, NAS is an O-methyltransferase agonist at the melatonin receptors MT, 1 MT, and 2 MT, and may be considered to be a 3 neurotransmitter. 3 4 5 In addition, NAS is distributed in some areas of the 6 brain where serotonin and melatonin are not, suggesting that it may have unique central duties of its own instead of merely functioning as a precursor in the synthesis of melatonin. 3
Recently, NAS has been shown to act as a
potent TrkB receptor agonist, while serotonin and melatonin are not. It produces robust 3 antidepressant, neuroprotective, and neurotrophic effects that are TrkB-mediated. In addition, AANAT 3 knockout mice which lack NAS display significantly greater immobility times versus control mice in assays of depression like the forced swim test. 3
NAS may also play a major role in the antidepressant effects of
selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). The SSRI 3 fluoxetine and the MAO-A inhibitor clorgyline upregulate AANAT indirectly through serotonergic mechanisms and thereby increase NAS levels after chronic administration, and this correlates with the onset of their antidepressant effects. 3 Furthermore, light exposure inhibits the synthesis of NAS and reduces the antidepressant effects of MAOIs. 7 These data strongly support a role for NAS in mood regulation and in antidepressant-induced therapeutic benefits. 3
Through a currently unidentified mechanism, NAS may be the cause of the
orthostatic hypotension seen with clinical treatment of MAOIs. 8 It reduces 7 blood pressure in rodents, and pinealectomy (the pineal gland being a major site of NAS and melatonin synthesis) abolishes the hypotensive effects of clorgyline. 8 Why orthostatic hypotension is commonly seen with MAOIs but not SSRIs (both of which increase NAS levels) however, is unknown. 7
^ AXELROD J, WEISSBACH H (April 1960). "Enzymatic O-methylation of N-acetylserotonin to melatonin". Science 131 (3409): 1312. doi: 10.1126/science.131.3409.1312. PMID 13795316.
^ WEISSBACH H, REDFIELD BG, AXELROD J (September 1960). "Biosynthesis of melatonin: enzymic conversion of serotonin to N-acetylserotonin". Biochimica et Biophysica Acta 43: 352–3. doi: 10.1016/0006-3002(60)90453-4. PMID 13784117.
^ a b c d e f g h Jang SW, Liu X, Pradoldej S, et al. (February 2010). "N-acetylserotonin activates TrkB receptor in a circadian rhythm". Proceedings of the National Academy of Sciences of the United States of America 107 (8): 3876. doi: 10.1073/pnas.0912531107. PMC 2840510. PMID 20133677.
^ Zhao H, Poon AM, Pang SF (March 2000). "Pharmacological characterization, molecular subtyping, and autoradiographic localization of putative melatonin receptors in uterine endometrium of estrous rats". Life Sciences 66 (17): 1581–91. doi: 10.1016/S0024-3205(00)00478-1. PMID 11261588.
^ Nonno R, Pannacci M, Lucini V, Angeloni D, Fraschini F, Stankov BM (July 1999). "Ligand efficacy and potency at recombinant human MT2 melatonin receptors: evidence for agonist activity of some mt1-antagonists". British Journal of Pharmacology 127 (5): 1288–94. doi: 10.1038/sj.bjp.0702658. PMC 1566130. PMID 10455277.
^ Paul P, Lahaye C, Delagrange P, Nicolas JP, Canet E, Boutin JA (July 1999). "Characterization of 2-[125I]iodomelatonin binding sites in Syrian hamster peripheral organs". The Journal of Pharmacology and Experimental Therapeutics 290 (1): 334–40. PMID 10381796.
^ a b c Oxenkrug GF (1999). "Antidepressive and antihypertensive effects of MAO-A inhibition: role of N-acetylserotonin. A review". Neurobiology (Budapest, Hungary) 7 (2): 213–24. PMID 10591054.
^ a b Oxenkrug GF (1997). "[N-acetylserotonin and hypotensive effect of MAO-A inhibitors]". Voprosy Meditsinskoi Khimii (in Russian) 43 (6): 522–6. PMID 9503569.