N -AcetylserotoninNames Preferred IUPAC name N -[2-(5-Hydroxy-1H -indol-3-yl)ethyl]acetamide
Other namesNAS;N -Acetyl-5-hydroxytryptamine; 5-Hydroxy-N -acetyltryptamine;N -Acetyl-5-HT; 5-HO-NAcT; 5-OH-NAcT
Identifiers ChEBI ChEMBL ChemSpider DrugBank ECHA InfoCard 100.013.560 MeSH N -AcetylserotoninN -AcetylserotoninUNII InChI=1S/C12H14N2O2/c1-8(15)13-5-4-9-7-14-12-3-2-10(16)6-11(9)12/h2-3,6-7,14,16H,4-5H2,1H3,(H,13,15)
Y Key: MVAWJSIDNICKHF-UHFFFAOYSA-N
Y InChI=1/C12H14N2O2/c1-8(15)13-5-4-9-7-14-12-3-2-10(16)6-11(9)12/h2-3,6-7,14,16H,4-5H2,1H3,(H,13,15)
Key: MVAWJSIDNICKHF-UHFFFAOYAX
Properties C 12 H 14 N 2 O 2 Molar mass −1 Density 1.268 g/mL Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
N -AcetylserotoninNAS ), also known asnormelatonin , is anaturally occurring chemicalintermediate in theendogenous production ofmelatonin fromserotonin .[ 1] [ 2] biological activity in its own right, including acting as amelatonin receptor agonist , anagonist of theTrkB , and havingantioxidant effects.
Biological function [ edit ] Like melatonin, NAS is anagonist at themelatonin receptors MT1 ,MT2 , andMT3 , and may be considered to be aneurotransmitter .[ 3] [ 4] [ 5] [ 6] brain where serotonin and melatonin are not, suggesting that it may have unique central duties of its own instead of merely functioning as aprecursor in thesynthesis of melatonin.[ 3] [ 7] [ 8] [ 8]
NAS has been shown to act as apotent TrkB receptor agonist, while serotonin and melatonin do not.[ 3] progenitor cells (NPC)s, blockage of TrkB abolished this effect suggesting that it is TrkB-dependent.[ 9] [ 9] [ 7]
Antioxidant properties [ edit ] NAS acts as a potentantioxidant , 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] lipid peroxidation in microsomes and mitochondria.[ 11] ROS in peripheral blood lymphocytes and to exhibit anti-oxidant effects against t-butylated hydroperoxide- and diamide-induced ROS.[ 12] nitric oxide synthase .[ 13]
Anti-inflammatory effects [ edit ] NAS has been reported to haveanti-inflammatory effects. NAS has been shown to inhibitLPS -stimulated production of theproinflammatory cytokine TNF-alpha in differentiated THP-1-derived human monocytes.[ 14]
NAS may play a role in the antidepressant effects ofselective serotonin reuptake inhibitors (SSRIs) andmonoamine oxidase inhibitors (MAOIs).[ 3] fluoxetine and theMAO-A inhibitor clorgyline upregulate AANAT indirectly throughserotonergic mechanisms and thereby increase NAS levels after chronic administration, and this correlates with the onset of their antidepressant effects.[ 3] [ 15] [ 3] knockout mice display significantly greater immobility times versus control mice inanimal models ofdepression .[ 3]
Through a currently unidentified mechanism, NAS may be the cause of theorthostatic hypotension seen with clinical treatment of MAOIs.[ 15] [ 16] blood pressure in rodents, andpinealectomy (thepineal gland being a major site of NAS and melatonin synthesis) abolishes thehypotensive effects ofclorgyline .[ 15] [ 16]
NAS is produced from serotonin by theenzyme aralkylamineN -acetyltransferase (AANAT) and is converted to melatonin byacetylserotoninO -methyltransferase (ASMT).
NAS is able to penetrate theblood–brain barrier , unlike serotonin.[ 17]
^ AXELROD J, WEISSBACH H (April 1960). "Enzymatic O-methylation of N-acetylserotonin to melatonin".Science .131 (3409): 1312.Bibcode :1960Sci...131.1312A .doi :10.1126/science.131.3409.1312 .PMID 13795316 .S2CID 22341451 . ^ 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 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– 81.Bibcode :2010PNAS..107.3876J .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.doi :10.1016/S0022-3565(24)34904-3 .PMID 10381796 . ^a b Tosini G., Ye K. & Iuvone PM (2012)."Neuroprotection, neurogenesis, and the sleepy brain" .Neuroscientist .18 (6):645– 653.doi :10.1177/1073858412446634 .PMC 3422380 PMID 22585341 . ^a b Oxenkrug G. & Ratner R. (2012)."N-acetylserotonin and aging-associated cognitive impairment and depression" .Aging Dis .3 (4):330– 338.PMC 3501368 PMID 23185714 . ^a b Sompol P.; Liu X.; Baba K.; Paul KN.; Tosini G.; Iuvone PM.; Ye K. (2011)."N-acetylserotonin promotes hippocampal neuroprogenitor cell proliferation in sleep-deprived mice" .Proc. Natl. Acad. Sci. U.S.A .108 (21):8844– 9.Bibcode :2011PNAS..108.8844S .doi :10.1073/pnas.1105114108 PMC 3102377 PMID 21555574 . ^ Oxenkrug G (2005). "Antioxidant effects of N-acetylserotonin: possible mechanisms and clinical implications".Ann. N. Y. Acad. Sci .1053 (1):334– 47.Bibcode :2005NYASA1053..334O .doi :10.1111/j.1749-6632.2005.tb00042.x .PMID 16179540 .S2CID 94273958 . ^ 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 .PMID 15357659 .S2CID 6974587 . ^ 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.Bibcode :1999FEBSL.449..206W .doi :10.1016/s0014-5793(99)00435-4 .PMID 10338133 .S2CID 32077728 . ^ Peter Klemm; Markus Hecker; Hannelore Stockhausen; Chin Chen Wu; Christoph Thiemermann (Aug 1995)."Inhibition by N-acetyl-5-hydroxytryptamine of nitric oxide synthase expression in cultured cells and in the anaesthetized rat" .Br J Pharmacol .115 (7):1175– 1181.doi :10.1111/j.1476-5381.1995.tb15021.x .PMC 1908794 PMID 7582541 . ^ Perianayagam MC.; Oxenkrug GF.; Jaber BL. (2005). "Immune-modulating effects of melatonin, N-acetylserotonin, and N-acetyldopamine".Ann. N. Y. Acad. Sci .1053 :386– 93.doi :10.1111/j.1749-6632.2005.tb00046.x .PMID 16179544 .S2CID 592935 . ^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 . ^ "N-Acetyl Serotonin" . DrugBank.
Food antioxidants Fuel antioxidants Measurements
Angiopoietin CNTF EGF (ErbB)
FGF
FGFR1 FGFR2 Agonists: Ersofermin FGF (1 ,2 (bFGF) ,3 ,4 ,5 ,6 ,7 (KGF ),8 ,9 ,10 (KGF2) ,17 ,18 ,22 )Palifermin Repifermin Selpercatinib Sprifermin Trafermin FGFR3 FGFR4 Unsorted
HGF (c-Met) IGF
LNGF (p75NTR ) PDGF RET (GFL)
SCF (c-Kit) TGFβ Trk
TrkA Negative allosteric modulators: VM-902A TrkB Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 TrkC
VEGF Others Additional growth factors: Adrenomedullin Colony-stimulating factors (seehere instead)Connective tissue growth factor (CTGF) Ephrins (A1 ,A2 ,A3 ,A4 ,A5 ,B1 ,B2 ,B3 )Erythropoietin (seehere instead)Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF) Glia maturation factor (GMF) Hepatoma-derived growth factor (HDGF) Interleukins /T-cell growth factors (seehere instead)Leukemia inhibitory factor (LIF) Macrophage-stimulating protein (MSP; HLP, HGFLP) Midkine (NEGF2) Migration-stimulating factor (MSF; PRG4) Oncomodulin Pituitary adenylate cyclase-activating peptide (PACAP) Pleiotrophin Renalase Thrombopoietin (seehere instead)Wnt signaling proteins Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)
MT1 Tooltip Melatonin receptor 1 MT2 Tooltip Melatonin receptor 2 Unsorted
Tryptamines 1-Methyl-DMT (1,N ,N -TMT, 1-TMT) 1-Methyl-T 2-HO-NMT 2-Methyl-DET 2-Methyl-DiPT 2-Methyl-iPALT (ASR-3002) 2,N ,N -TMT (2-methyl-DMT) 3-IAAR 4-Fluoro-DMT 4-Fluoro-T 5-Bromo-DMT 5-Bromo-T 5-Chloro-DMT 5-Chloro-T 5-CT 5-Ethyl-DMT 5-Fluoro-DET 5-Fluoro-DMT 5-Fluoro-EPT 5-Fluoro-T 5-Me-MiPT 5-MeS-DMT 5-Methyl-DMT 5-Methyl-T 6-Fluoro-DET 6-Fluoro-DMT 6-Fluoro-T 6-HO-DET 6-HO-DMT 6-HO-T (6-HT) 6-MeO-DMT 6-MeO-T 6-Methyl-T 6,7-DHT 7-Chloro-T 7-HO-T (7-HT) 7-MeO-DMT 7-MeO-T 7-Methyl-DMT 7-Methyl-T Acetryptine (5-AT) Almotriptan Benzotript (4-CB-Trp) BGE Bretisilocin (5-fluoro-MET; GM-2505) Convolutindole A (2,4,6-TBr,1,7-DiMeO-DMT) DALT DAT DBT Desformylflustrabromine DET (T-9) DHT DiPT DMT DPT E-6801 E-6837 EB-003 EiPT EPT FGIN-127 FGIN-143 Idalopirdine iPALT (ALiPT; ASR-3003) Lespedamine (1-MeO-DMT) L-694247 MBT MET MiPT MPT MsBT N -Benzyltryptamine (T-NB, NB-T)N -DEAOP-NETN -DEAOP-NMTNAT NBoc-DMT NET/NETP NHT NiPT NMT NsBT NtBT PALT (ASR-3004) PiPT Rizatriptan ST-1936 (2-Me-5-Cl-DMT) Sumatriptan TCS-1205 Tryptamine (T; indolylethylamine) Tryptophan (Trp) WAY-181187 Yuremamine Z2876442907 Zolmitriptan 4-Hydroxytryptamines esters /ethers 5-Hydroxy- and5-methoxytryptamines 2-Methyl-5-HT 2-Methyl-5-MeO-DALT 4-HO-5-MeO-T 4-F-5-MeO-DMT 4,5-DHP-DMT 4,5-DHT 4,5-MDO-DMT 4,5-MDO-DiPT 5-BT 5-Ethoxy-DMT 5-HO-DET 5-HO-DiPT 5-HO-NiPT 5-HO-DPT 5-HTP (oxitriptan )5-MeO-2-TMT 5-MeO-34MPEMT 5-MeO-7,N ,N -TMT 5-MeO-DALT 5-MeO-DBT 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT (N ,N ,O -TMS;O -methylbufotenine) 5-MeO-DPT 5-MeO-EiPT 5-MeO-EPT 5-MeO-MALT 5-MeO-MET 5-MeO-MiPT 5-MeO-NET 5-MeO-NiPT 5-MeO-NMT (O ,N -DMS) 5-MeO-PiPT 5-MeO-NBpBrT 5-MeO-T (5-MT; mexamine;O -methylserotonin) 5-MeO-T-NBOMe 5-MT-NB3OMe 5-NOT 5,6-DHT 5,6-MDO-DiPT 5,6-MDO-DMT 5,6-MDO-MiPT 5,6-MeO-MiPT 5,7-DHT Arachidonoyl serotonin ASR-3001 (5-MeO-iPALT) BAB Benanserin (BAS; SQ-4788) BGC20-761 Bufotenidine (5-HTQ;N ,N ,N -TMS) Bufotenin (5-HO-DMT;N ,N -DMS; mappine) Bufoviridine (5-SO-DMT) CP-132,484 Cqd 280 Cqd 285 Cqdd 280 Donitriptan EMDT (2-Et-5-MeO-DMT) HIOC Indorenate (TR-3369) Isamide (N -CA-5-MT) L-741604 MS-245 N -DEAOP-5-MeO-NETN -DEAOP-5-MeO-NMTN -Feruloylserotonin (moschamine)Norbufotenin (5-HO-NMT; NMS) O -Acetylbufotenine (5-AcO-DMT)O -Pivalylbufotenine (5-t -BuCO-DMT)Psilomethoxin (4-HO-5-MeO-DMT) Psilomethoxybin (4-PO-5-MeO-DMT) Serotonin (5-HT) N -Acetyltryptaminesα-Alkyltryptamines 5-Hydroxy- and 5-alkoxy-α-alkyltryptamines: 1-Pr-5-MeO-AMT 5-Allyloxy-AMT 5-Ethoxy-αMT 5-iPrO-αMT 5-MeO-αET 5-MeO-αMT (α,O -DMS; Alpha-O) α-Methyl-5-HTP α-Methylmelatonin α-Methylserotonin (5-HO-αMT; α-Me-5-HT) α,N ,O -TMS (5-MeO-α,N -DMT) α,N ,N ,O -TeMS (5-MeO-α,N ,N -TMT) AL-37350A (4,5-DHP-αMT) BW-723C86 Cyclized tryptamines 5-MeO-IsoqT Barettin Cyclic 3-OHM Ergolines andlysergamides (e.g.,LSD )Harmala alkaloidsβ-carbolines (e.g.,5-methoxyharmalan ,6-MeO-THH ,6-methoxyharmalan ,9-Me-BC ,β-carboline (norharman) ,fenharmane ,harmaline ,harmalol ,harmane ,harmine ,LY-266,097 ,pinoline ,tetrahydroharmine ,tryptoline )Iboga alkaloidsibogaine ,ibogamine ,noribogaine ,tabernanthine )Ibogalogs (e.g.,catharanthalog ,fluorogainalog ,ibogainalog ,ibogaminalog (DM-506) ,LS-22925 ,noribogainalog ,noribogaminalog ,PHA-57378 ,PNU-22394 ,tabernanthalog )Imidazolylindoles (e.g.,AGH-107 ,AGH-192 ,AH-494 )Metralindole Morpholinylethylindoles (e.g.,mor-T ,5-MeO-mor-T )Partial ergolines and lysergamides (e.g.,NDTDI ,RU-27849 ,RU-28251 ,RU-28306 ,FHATHBIN ,LY-178210 ,Bay R 1531 (LY-197206) ,LY-293284 ,10,11-seco-LSD ,10,11-secoergoline (α,N -Pip-T) ,CT-5252 )Pertines (e.g.,alpertine ,milipertine ,oxypertine ,solypertine )Piperidinylethylindoles (e.g.,pip-T ,5-MeO-pip-T ,indolylethylfentanyl )Pyrrolidinylethylindoles (e.g.,pyr-T ,4-HO-pyr-T ,5-MeO-pyr-T ,4-F-5-MeO-pyr-T )Pyrrolidinylmethylindoles (e.g.,MPMI ,4-HO-MPMI (lucigenol) ,5F-MPMI ,5-MeO-MPMI ,CP-122288 ,CP-135807 ,eletriptan )Tetrahydrocarbazolamines (e.g.,ciclindole ,flucindole ,frovatriptan ,LY-344864 ,ramatroban )Tetrahydropyridinylindoles (e.g.,RS134-49 ,RU-28253 ,NEtPhOH-THPI )Tetrahydropyrroloquinolines (e.g.,bufothionine ,O -methylnordehydrobufotenineYohimbans (e.g.,yohimbine ,rauwolscine ,spegatrine ,corynanthine ,ajmalicine ,reserpine ,deserpidine ,rescinnamine )Isotryptamines Related compounds 2-Azapsilocin 4-Aza-5-MeO-DPT 5-Aza-4-MeO-DiPT 5-HIAA 5-HIAL 5-HITCA 5-MIAL 7-Aza-5-MeO-DiPT α-Carboline γ-Carbolines (pyridoindoles) (e.g.,γ-carboline ,alosetron ,gevotroline ,latrepirdine ,lurosetron ,mebhydrolin ,tiflucarbine )Amedalin Benzindopyrine Benzofurans (e.g.,3-APB ,5-MeO-DiBF ,BPAP ,3-F-BPAP ,dimemebfe ,mebfap ,oxa-noribogaine )Benzothiophenes (e.g.,3-APBT )Carmoxirole CT-4436 Daledalin Gramine Histamine Homotryptamines (e.g.,HT ,DMHT )I-32 IAL IN-399 Indazolethylamines (e.g.,AL-34662 ,AL-38022A ,O -methyl-AL-34662VU6067416 ,YM-348 )Indenylethylamines (e.g.,C-DMT )Indolizinylethylamines (e.g.,TACT908 (2ZEDMA) ,1ZP2MA ,1Z2MAP1O )Indolylaminopropanes (e.g.,1-API ,2-API ,4-API ,5-API (5-IT; PAL-571) ,6-API (6-IT) ,7-API )Iprindole Masupirdine Medmain Molindone Non-tryptaminetriptans (e.g.,avitriptan ,LY-334370 ,naratriptan ) Ondansetron Oxazinopyridoindoles (e.g.,IHCH-8134 )Phenethylamines (e.g.,phenethylamine ,amphetamine )Piperidinylbenzimidazolines (e.g.,benperidol ,timiperone )Piperazinylbenzisothiazoles (e.g.,lurasidone ,perospirone ,tiospirone ,ziprasidone )Piperidinylbenzisoxazoles (e.g.,iloperidone ,milsaperidone ,ocaperidone ,paliperidone ,risperidone )Piperidinylindoles (e.g.,BRL-54443 ,LY-334370 ,naratriptan ,sertindole ,SN-22 )Pirlindole Pyridinylbenzimidazoles (e.g.,droperidol )Pyridinylindoles (e.g.,tepirindole )Pyridopyrroloquinoxalines (e.g.,IHCH-7113 ,IHCH-7079 ,IHCH-7086 ,lumateperone ,deulumateperone ,ITI-1549 )Pyrrolylethylamines (e.g.,2-pyrrolylethylamine (NEA) ,3-pyrrolylethylamine (3-NEA) ,3-pyrrolylpropylamine )Pyrrolopyridinylethylamines (e.g.,WAY-208466 )Quinolinylethylamines (e.g.,mefloquine )Ro60-0213 Selisistat Tetrahydropyridinylindoles (e.g.,EMD-386088 ,LY-367265 ,RU-24,969 )Tetrahydropyridinylpyrrolopyridines (e.g.,(R )-69 (3IQ) ,(R )-70 ,CP-94253 )Tetrindole Tipindole Zilpaterol (RU-42173)
