褪黑素

**褪黑素**
臨床資料
AHFS（英語：American Society of Health-System Pharmacists）/Drugs.com	消費者藥物信息
給藥途徑	口服、舌下、皮膚
ATC碼	N05CH01 (WHO) ;
法律規範狀態
法律規範	澳：限醫生處方（S4）; 英：處方藥（℞-only） (POM); 美：OTC;
藥物動力學數據
生物利用度	30–50%
藥物代謝	肝臟 via CYP1A2 mediated 6-hydroxylation
生物半衰期	35–50 分鐘
排泄途徑	腎臟
識別資訊
	IUPAC命名法 N-[2-(5-methoxy-1H-indol-3-yl)ethyl]; acetamide; ;
CAS號	73-31-4
PubChem CID	896;
IUPHAR/BPS	224;
DrugBank	DB01065 ;
ChemSpider	872 ;
UNII	JL5DK93RCL;
KEGG	D08170 ;
ChEBI	CHEBI:16796 ;
ChEMBL	ChEMBL45 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID1022421 ;
ECHA InfoCard	100.000.725
化學資訊
化學式	C13H16N2O2
摩爾質量	232.278 g/mol
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES COC1=CC2=C(NC=C2CCNC(C)=O)C=C1;
	InChI InChI=1S/C13H16N2O2/c1-9(16)14-6-5-10-8-15-13-4-3-11(17-2)7-12(10)13/h3-4,7-8,15H,5-6H2,1-2H3,(H,14,16) ; Key:DRLFMBDRBRZALE-UHFFFAOYSA-N ;

褪黑素（或稱褪黑激素、松果體素或美拉托寧，英語：melatonin），化學名為N-乙醯基-5-甲氧基色胺^[1]，是一種生命必需的小分子吲哚胺類物質^[2]，在動物、植物、真菌和細菌中皆有發現。在動物體內，褪黑素是一種調節生物鐘的激素^[3]；而其作用在其他生物體內可能不同，同樣，褪黑素在動物體內的合成過程也不同於其他物種^[4]。

褪黑素可以用來幫助入睡和治療睡眠障礙。其可以口服也可以通過噴霧或透皮貼劑的方式給藥。褪黑素在美國和加拿大是非處方藥，在中國大陸為保健食品（如腦白金的主要成分）。

歷史[編輯]

20世紀初的人發現有一種物質可以使蛙皮中的黑色素褪變成白色^[2]。1958年從牛的松果體內分離提取出該物質，並命名為褪黑素^[5]。

人們開始普遍認為褪黑素僅在動物體內存在。隨著研究發展，才發現細菌、微生物、真菌、藻類以及植物也有褪黑素^[6]。

生成[編輯]

在高等動物中，褪黑素是由松果體中的松果體細胞將色氨酸在四種酶的作用下經四步連續酶促反應轉化而成^[7]。松果體產生的褪黑素是內分泌激素，會進入血液；視網膜和胃腸道則產生旁泌性激素。下視丘的視交叉上核（英語：Suprachiasmatic nucleus）會由視網膜接收每日光暗的規律，從而影響褪黑素的製造。

植物體內的褪黑素也是由色氨酸經過四步連續酶促反應轉化而成，但至少需要六種酶參與^[8]。

在人體內，5-羥色胺（又稱血清素）在N-乙醯基轉移酶催化下與乙醯輔酶A反應成N-乙醯-5-羥色胺，然後S-腺苷甲硫氨酸在乙醯血清素O-甲基轉移酶（英語：Acetylserotonin O-methyltransferase）催化下甲基化N-乙醯-5-羥色胺為褪黑素。

稻米等植物也會製造褪黑素，哺乳類動物進食含褪黑素的食物後會吸收褪黑素，溶入體內的褪黑素^[9]^[10]。

功效[編輯]

在動物中，褪黑激素參與同步晝夜節律，包括睡眠－覺醒時間、血壓調節和季節性繁殖。它的大部分作用是激活褪黑激素受體，而另一部分則是它作為抗氧化劑的作用。在植物中，它具有抵抗氧化應激的作用^[2]，還可促進種子萌發、調節植物的碳氮代謝、果實發育以及改善果實品質和產量^[11]。褪黑激素也存在於各種食物中。但中央神經系統才是控制內分泌系統及旁泌性系統的主要組織（曾被人誤認為褪黑素）^[12]^[13]。

製造機制[編輯]

在正常情況，視網膜感知環境中的藍光亮度，發出光暗信號並傳遞給松果體，令其在黑暗中製造褪黑素，因此褪黑素亦稱「黑暗荷爾蒙」。褪黑素的分泌於晚間中段時間最多，然後在晚間後段時間較少、再隨時間逐漸減少至天明。在古代，在溫帶生活的人於冬季會有十到八小時生活在黑暗當中，而篝火和白熾燈的光中藍光的成分很少；反之，現代人廣泛使用日光燈，身處黑暗的時間減至八小時以下。即使是微弱燈光下褪黑素的生成都會受一定程度影響，在強光下的影響就更大。缺乏褪黑素很可能使夜班工作者得癌病^[14]，而現代於晚間亮燈的習慣亦可能使發達國家越來越多人得癌症^[15]。

參見[編輯]

參考文獻[編輯]

^ Melatonin. Sleepdex. [17 August 2011]. （原始內容存檔於2015-09-24）.
^ ^2.0 ^2.1 ^2.2 Liu, Deshuai; Yao, Lei; Xu, Weirong; Feng, Mei; Yao, Wenkong. Research Progress of Melatonin in Plant Stress Resistance. Chinese Bulletin of Botany. 2022-01-01, 57 (1): 111. doi:10.11983/CBB21146.
^ Hardeland, Rüdiger; Pandi-Perumal, S.R.; Cardinali, Daniel P. Melatonin. The International Journal of Biochemistry & Cell Biology. 2006, 38 (3): 313–316. PMID 16219483. doi:10.1016/j.biocel.2005.08.020.
^ Lewis, Alan. Melatonin and the Biological Clock. McGraw-Hill. 1999: 7. ISBN 0879837349 （英語）.
^ Lerner, Aaron B.; Case, James D.; Takahashi, Yoshiyata; Lee, Teh H.; Mori, Wataru. ISOLATION OF MELATONIN, THE PINEAL GLAND FACTOR THAT LIGHTENS MELANOCYTES 1. Journal of the American Chemical Society. 1958-05, 80 (10): 2587–2587. doi:10.1021/ja01543a060.
^ Tan, Dun-Xian; Manchester, Lucien C.; Hardeland, Rüdiger; Lopez-Burillo, Silvia; Mayo, Juan C.; Sainz, Rosa M.; Reiter, Russel J. Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin: Melatonin: a multi-functional molecule. Journal of Pineal Research. 2003-01, 34 (1): 75–78. doi:10.1034/j.1600-079X.2003.02111.x.
^ Fernández-Mar, M.I.; Mateos, R.; García-Parrilla, M.C.; Puertas, B.; Cantos-Villar, E. Bioactive compounds in wine: Resveratrol, hydroxytyrosol and melatonin: A review. Food Chemistry. 2012-02, 130 (4): 797–813. doi:10.1016/j.foodchem.2011.08.023.
^ Back, Kyoungwhan; Tan, Dun-Xian; Reiter, Russel J. Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts. Journal of Pineal Research. 2016-11, 61 (4): 426–437. doi:10.1111/jpi.12364.
^ Hattori A, Migitaka H, Iigo M, Itoh M, Yamamoto K, Ohtani-Kaneko R, Hara M, Suzuki T, Reiter R. Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates.. Biochem Mol Biol Int. 1995, 35 (3): 627–34. PMID 7773197.
^ Uz T, Arslan A, Kurtuncu M, Imbesi M, Akhisaroglu M, Dwivedi Y, Pandey G, Manev H. The regional and cellular expression profile of the melatonin receptor MT1 in the central dopaminergic system.. Brain Res Mol Brain Res. 2005, 136 (1-2): 45–53. PMID 15893586.
^ Erdal, Serkan. Melatonin promotes plant growth by maintaining integration and coordination between carbon and nitrogen metabolisms. Plant Cell Reports. 2019-08, 38 (8): 1001–1012. doi:10.1007/s00299-019-02423-z.
^ Richardson G. The human circadian system in normal and disordered sleep.. J Clin Psychiatry. 2005,. 66 Suppl 9: 3–9; quiz 42–3. PMID 16336035.
^ Perreau-Lenz S, Pévet P, Buijs R, Kalsbeek A. The biological clock: the bodyguard of temporal homeostasis.. Chronobiol Int. 2004, 21 (1): 1–25. PMID 15129821.
^ Schernhammer E, Rosner B, Willett W, Laden F, Colditz G, Hankinson S. Epidemiology of urinary melatonin in women and its relation to other hormones and night work.. Cancer Epidemiol Biomarkers Prev. 2004, 13 (62): 936–43. PMID 15184249.
^ Pauley S. Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue.. Med Hypotheses. 2004, 63 (4): 588–96. PMID 15325001.

外部連結[編輯]

Melatonin information（頁面存檔備份，存於網際網路檔案館）from MedlinePlus
Melatonin entry in TiHKAL • info（頁面存檔備份，存於網際網路檔案館）

[1] Melatonin. Sleepdex. [17 August 2011]. （原始內容存檔於2015-09-24）.

[CBB21146-2] 2.0 ^2.1 ^2.2 Liu, Deshuai; Yao, Lei; Xu, Weirong; Feng, Mei; Yao, Wenkong. Research Progress of Melatonin in Plant Stress Resistance. Chinese Bulletin of Botany. 2022-01-01, 57 (1): 111. doi:10.11983/CBB21146.

[3] Hardeland, Rüdiger; Pandi-Perumal, S.R.; Cardinali, Daniel P. Melatonin. The International Journal of Biochemistry & Cell Biology. 2006, 38 (3): 313–316. PMID 16219483. doi:10.1016/j.biocel.2005.08.020.

[4] Lewis, Alan. Melatonin and the Biological Clock. McGraw-Hill. 1999: 7. ISBN 0879837349 （英語）.

[5] Lerner, Aaron B.; Case, James D.; Takahashi, Yoshiyata; Lee, Teh H.; Mori, Wataru. ISOLATION OF MELATONIN, THE PINEAL GLAND FACTOR THAT LIGHTENS MELANOCYTES 1. Journal of the American Chemical Society. 1958-05, 80 (10): 2587–2587. doi:10.1021/ja01543a060.

[6] Tan, Dun-Xian; Manchester, Lucien C.; Hardeland, Rüdiger; Lopez-Burillo, Silvia; Mayo, Juan C.; Sainz, Rosa M.; Reiter, Russel J. Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin: Melatonin: a multi-functional molecule. Journal of Pineal Research. 2003-01, 34 (1): 75–78. doi:10.1034/j.1600-079X.2003.02111.x.

[7] Fernández-Mar, M.I.; Mateos, R.; García-Parrilla, M.C.; Puertas, B.; Cantos-Villar, E. Bioactive compounds in wine: Resveratrol, hydroxytyrosol and melatonin: A review. Food Chemistry. 2012-02, 130 (4): 797–813. doi:10.1016/j.foodchem.2011.08.023.

[8] Back, Kyoungwhan; Tan, Dun-Xian; Reiter, Russel J. Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts. Journal of Pineal Research. 2016-11, 61 (4): 426–437. doi:10.1111/jpi.12364.

[Hattori1995-9] Hattori A, Migitaka H, Iigo M, Itoh M, Yamamoto K, Ohtani-Kaneko R, Hara M, Suzuki T, Reiter R. Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates.. Biochem Mol Biol Int. 1995, 35 (3): 627–34. PMID 7773197.

[Uz2005-10] Uz T, Arslan A, Kurtuncu M, Imbesi M, Akhisaroglu M, Dwivedi Y, Pandey G, Manev H. The regional and cellular expression profile of the melatonin receptor MT1 in the central dopaminergic system.. Brain Res Mol Brain Res. 2005, 136 (1-2): 45–53. PMID 15893586.

[11] Erdal, Serkan. Melatonin promotes plant growth by maintaining integration and coordination between carbon and nitrogen metabolisms. Plant Cell Reports. 2019-08, 38 (8): 1001–1012. doi:10.1007/s00299-019-02423-z.

[Richardson2005-12] Richardson G. The human circadian system in normal and disordered sleep.. J Clin Psychiatry. 2005,. 66 Suppl 9: 3–9; quiz 42–3. PMID 16336035.

[Perreau-Lenz2004-13] Perreau-Lenz S, Pévet P, Buijs R, Kalsbeek A. The biological clock: the bodyguard of temporal homeostasis.. Chronobiol Int. 2004, 21 (1): 1–25. PMID 15129821.

[Schernhammer2004-14] Schernhammer E, Rosner B, Willett W, Laden F, Colditz G, Hankinson S. Epidemiology of urinary melatonin in women and its relation to other hormones and night work.. Cancer Epidemiol Biomarkers Prev. 2004, 13 (62): 936–43. PMID 15184249.

[Pauley2004-15] Pauley S. Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue.. Med Hypotheses. 2004, 63 (4): 588–96. PMID 15325001.

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褪黑素

目次