Like melatonin, NAS is an
agonist at the
melatonin receptorsMT1,
MT2, and
MT3, and may be considered to be a
neurotransmitter.[3][4][5][6] In addition, NAS is distributed in some areas of the
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] NAS is known to have anti-depressant, neurotrophic and cognition-enhancing effects [7][8] and has been proposed to be a target for the treatment of aging-associated cognitive decline and depression [8]
TrkB receptor
NAS has been shown to act as a
potentTrkB receptor agonist, while serotonin and melatonin do not.[3] Subchronic and chronic administration of NAS to adult mice induces proliferation of neural
progenitor cells (NPC)s, blockage of TrkB abolished this effect suggesting that it is TrkB-dependent.[9] NAS was also found to significantly enhance NPC proliferation in sleep-deprived mice.[9] It is thought that the anti-depressant and neurotrophic effects of NAS are in part due to its role as a TrkB agonist.[7]
Antioxidant properties
NAS acts as a potent
antioxidant, NAS effectiveness as an anti-oxidant has been found to be different depending on the experimental model used, it has been described as being between 5 and 20 times more effect than melatonin at protecting against oxidant damage.[10] NAS has been shown to protect against
lipid peroxidation in microsomes and mitochondria.[11] NAS has also been reported to lower resting levels of
ROS in peripheral blood lymphocytes and to exhibit anti-oxidant effects against t-butylated hydroperoxide- and diamide-induced ROS.[12] NAS has also been observed to inhibit
nitric oxide synthase.[13]
NAS may play a role in the antidepressant effects of
selective serotonin reuptake inhibitors (SSRIs) and
monoamine oxidase inhibitors (MAOIs).[3] The SSRI
fluoxetine and the
MAO-Ainhibitorclorgylineupregulate AANAT indirectly through
serotonergic mechanisms and thereby increase NAS levels after chronic administration, and this correlates with the onset of their antidepressant effects.[3][15] Furthermore, light exposure inhibits the synthesis of NAS and reduces the antidepressant effects of MAOIs.[3] In addition, AANAT
knockout mice display significantly greater immobility times versus control mice in
animal models of
depression.[3] These data support a potential role for NAS in mood regulation and in antidepressant-induced therapeutic benefits.
^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.
PMID11261588.
^Gavazza MB.; Català A. (2004). "Protective effect of N-acetyl-serotonin on the nonenzymatic lipid peroxidation in rat testicular microsomes and mitochondria". J. Pineal Res. 37 (3): 153–60.
doi:
10.1111/j.1600-079x.2004.00150.x.
PMID15357659.
S2CID6974587.
^Wölfler A.; Abuja PM.; Schauenstein K.; Liebmann PM. (1999). "N-acetylserotonin is a better extra- and intracellular antioxidant than melatonin". FEBS Lett. 449 (2–3): 206–10.
doi:
10.1016/s0014-5793(99)00435-4.
PMID10338133.
S2CID32077728.
^
abcOxenkrug GF (1999). "Antidepressive and antihypertensive effects of MAO-A inhibition: role of N-acetylserotonin. A review". Neurobiology (Budapest, Hungary). 7 (2): 213–24.
PMID10591054.
^
abOxenkrug GF (1997). "[N-acetylserotonin and hypotensive effect of MAO-A inhibitors]". Voprosy Meditsinskoi Khimii (in Russian). 43 (6): 522–6.
PMID9503569.