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催產素 (藥物)

维基百科，自由的百科全书
此條目介紹的是催產素的藥物。关于此一哺乳動物激素，请见「催產素」。
维基百科中的醫學内容仅供参考，並不能視作專業意見。如需獲取醫療幫助或意見，请咨询专业人士。詳見醫學聲明。
催產素 (藥物)
臨床資料
读音/ˌɒksɪˈtoʊsɪn/
商品名Pitocin、Syntocinon、Viatocinon及其他
AHFS/Drugs.comMonograph
MedlinePlusa682685
核准狀況
懷孕分級
给药途径鼻腔給藥,靜脈注射,肌肉注射
ATC碼
法律規範狀態
法律規範
藥物動力學數據
药物代谢肝臟及其他 (經由催產素酶)
生物半衰期1–6分鐘(靜脈注射)
~2小時 (鼻腔給藥)[4][5]
排泄途徑膽管及腎臟
识别信息
  • 1-({(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-(4-hydroxybenzyl)-13-[(1S)-1-methylpropyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl}carbonyl)-L-prolyl-L-leucylglycinamide
CAS号50-56-6 checkY
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
化学信息
化学式C43H66N12O12S2
摩尔质量1,007.19 g·mol−1
3D模型（JSmol）
  • CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](N)CSSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O
  • InChI=1S/C43H66N12O12S2/c1-5-22(4)35-42(66)49-26(12-13-32(45)57)38(62)51-29(17-33(46)58)39(63)53-30(20-69-68-19-25(44)36(60)50-28(40(64)54-35)16-23-8-10-24(56)11-9-23)43(67)55-14-6-7-31(55)41(65)52-27(15-21(2)3)37(61)48-18-34(47)59/h8-11,21-22,25-31,35,56H,5-7,12-20,44H2,1-4H3,(H2,45,57)(H2,46,58)(H2,47,59)(H,48,61)(H,49,66)(H,50,60)(H,51,62)(H,52,65)(H,53,63)(H,54,64)/t22-,25-,26-,27-,28-,29-,30-,31-,35-/m0/s1 checkY
  • Key:XNOPRXBHLZRZKH-DSZYJQQASA-N checkY

人工合成的催產素（INN:oxytocin）是一種由催產素肽製成的藥物，以Pitocin等品牌名稱於市場上銷售。[6][7]它被用於引起子宮收縮，以啟動分娩、加快分娩速度，並在分娩後幫助止血。[6]

此藥物的給藥途徑為肌肉注射，或是靜脈注射。[6]

催產素也以鼻腔噴霧（鼻腔給藥）的形式供應，作為精神醫學、內分泌系統和體重管理用途的補充劑。鼻腔噴霧形式的催產素，主要是沿著嗅神經穿越血腦屏障，到達大腦的嗅球，那裡密集的大細胞催產素神經元能快速接收神經衝動，而達到前述精神醫學等目的，與注射形式的作用途徑不同。

天然存在的催產素於1906年被發現，[8][9]而人工合成的催產素已列入世界衛生組織基本藥物標準清單之中。[10]

醫療用途

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催產素經由靜脈輸注可用於引產，或是孕婦在催產素激發試驗（英语：oxytocin challenge test）結果不理想時，用於支持分娩進程緩慢的情況。透過進行催產素刺激的分娩過程，與自然分娩的過程相似。[11]催產素與其他引產方法相比，會較少導致子宮收縮過速（定義為在30分鐘內，平均每10分鐘超過5次。子宮收縮過速可能，但不一定會造成胎兒窘迫）。此外，若配合人工破膜（英语：Artificial rupture of membranes），此藥物能讓分娩進程更快。[12][13]對於引產，使用高劑量是否會優於用標準劑量的，目前尚未經充分研究。此藥物已很大程度上取代麥角新鹼用於治療急性產後出血，而成為增加子宮張力的主要藥物。催產素也在獸醫學中用於幫助分娩和刺激泌乳。

雖然催產素能引起乳汁噴出反射，但尚未發現其能提高母乳哺育的成功率。[14]

禁忌症

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人工合成的催產素注射液在以下任一情況下均禁用：[15]

  • 顯著的頭盆不稱（英语：Cephalopelvic disproportion）
  • 胎位或胎勢不良（例如橫位），分娩前若無法轉位則無法自然分娩
  • 產科急症，此時母體或胎兒的風險/效益比傾向採用手術分娩
  • 分娩尚未迫在眉睫，卻出現胎兒窘迫
  • 臍帶脫垂（英语：Umbilical cord prolapse）
  • 子宮活動未能充分進展
  • 子宮過度活躍或子宮張力過高
  • 陰道分娩成為禁忌症（例如母體有侵襲性子宮頸癌、活動性生殖器疱疹感染、完全性前置胎盤、前置血管（英语：vasa previa）、臍帶先露或脫垂）
  • 母體曾因剖腹產或重大的子宮頸或子宮手術（例如穿過子宮底部手術）而有子宮或子宮頸瘢痕
  • 胎頭未入盆
  • 個體對催產素或製劑中任何成分有過敏史

副作用

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依建議劑量使用催產素相對安全，且副作用不常出現。[16]以下是曾報導過，發生於母體的藥物不良反應：[16]

這些副作用中很多，很難判斷究竟是催產素用藥本身所造成，還是正常分娩本身已有的風險。[17][11]

分娩時使用催產素與顯著更高的嚴重產後出血風險相關。[18]

已知過量或是長期給藥（持續24小時或更久）可能導致子宮強直性收縮（英语：tetanic contraction）、子宮破裂，有時甚至是致命性。在給藥過程中可能會出現水中毒現象，症狀包括癲癇發作、昏迷、新生兒黃疸，並可能導致死亡。[19]研究顯示要安全使用催產素，管理液體攝入量並持續監測鈉水平極為重要。[20]

在分娩時使用催產素，與需要更多醫療介入的情況有關聯，其中最主要的是透過使用硬脊膜外麻醉時。[21]根據記錄，這會為產生一種"連鎖反應"，可能對分娩過程造成有害影響。[22][23]不過使用催產素，反能降低剖腹產率，[24]同時也能顯著縮短分娩的持續時間。[24]此外，早期使用催產素進行催產，也被證實能增加自然陰道分娩的機率，並降低絨毛羊膜炎或子宮內感染的風險。[25][26]

研究人員於2013年在《美國醫學會兒科學雜誌（英语：JAMA Pediatrics）》上發表一項具里程碑意義的研究報告以來，[27]關於在分娩時使用催產素，與兒童發育過程中自閉症類群障礙（ASD）風險增加之間有潛在關聯，便成為一個爭論性話題。[28]然而目前沒有確鑿的證據支持催產素會導致自閉症類群障礙或是其他神經發育障礙。[29]

催產素於2012年被美國安全用藥實踐協會（Institute for Safe Medication Practices）列入急症護理環境下的"高警訊藥物"列表。[30]列表所含藥物如果給藥不當，會帶來具高風險的危害。[30]

個體在懷孕期間，子宮活動力增加會導致胎兒或新生兒出現心率下降、心律不整、癲癇發作、腦損傷，甚至是死亡。[16]然而，子宮活動力增加是自然分娩和引產的共同特徵，與之相關的風險並非催產素所獨有。[11]

使用催產素的與產婦罹患產後憂鬱症的風險增加有關聯。[31]

中樞給予催產素會損害某些學習和記憶功能。[32]此外，全身性給藥在某些厭惡性記憶任務（研究生物體如何形成和提取與不愉快、恐懼或疼痛相關的記憶）中會損害記憶提取。[33]然而，催產素似乎能促進專門針對社交資訊的學習與記憶。研究顯示健康男性在給予鼻腔催產素後，對人臉，尤其是快樂的臉孔的記憶力有所改善。[34][35]

藥效學

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研究發現催產素除作為催產素受體激動劑外，也能作為μ-和κ-阿片類受體的變構調節劑（英语：allosteric modulator）（PAM）。這可能與其具鎮痛作用有關。[36][37][38][39][40][41]

藥物動力學

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一用於靜脈輸注的催產素液袋。

給藥途徑

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1國際單位（IU）的催產素約等於1.68微克（µg，或mcg）的純催產素肽。[42]

  • 注射：催產素的臨床劑量通常以肌肉注射或是靜脈注射的方式給予，以引起子宮收縮。[6]從周邊給藥時，極少量的催產素（小於1%）似乎會進入人體的中樞神經系統。[43]此化合物經靜脈注射後，在血液中的生物半衰期通常約為3分鐘。靜脈給藥需要40分鐘才能達到穩態濃度，並實現最大的子宮收縮反應。[44]
  • 頰側給藥（英语：Buccal administration）：過去曾以頰側含片的方式給予催產素，但已不再是常見的做法。[45]
  • 舌下給藥：舌下的吸收效果很差。[46]
  • 鼻腔給藥:藥物經由鼻腔噴霧給藥後能能可靠地穿過血腦屏障後進入大腦，進而對人體產生精神作用。[47][48]尚未有關於短期使用18~40國際單位（36-80微克）催產素的嚴重不良反應記錄。[49]此給藥方式的中樞作用持續時間至少為2.25小時，最長可達4小時。[4][5]
  • 口服：雖然最初認為口服方式會導致催產素在胃腸道中受到破壞，但研究顯示催產素能通過免疫球蛋白RAGE（晚期糖基化終產物受體）穿過腸上皮並進入血液中。研究顯示口服的催產素會增加人類對面部情緒的殼核（英语：putamen）反應（即人類口服催產素後，他們大腦中的殼核在觀看對方臉部情緒時，會表現出更強烈的神經反應）。[50]口服催產素對人類行為與大腦功能產生的影響，與鼻腔給藥不同，可能與其分子運輸和結合機制的差異有關。

化學

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作用與催產素相似的胜肽類似物，例如：卡貝縮宮素（商品名稱：Duratocin）和地莫催產素（英语：Demoxytocin）（商品名稱：Sandopart），已被開發，且上市用於醫療用途。[51]此外，小分子催產素受體激動劑，例如：TC OT 39（英语：TC OT 39）、WAY-267464（英语：WAY-267464）和LIT-001（英语：LIT-001），也已獲得開發與研究。[51]然而，由於它們對抗利尿激素（血管升壓素）受體缺乏選擇性，這類小分子催產素受體激動劑的潛在用途迄今仍然有限。[51]

歷史

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催產素的子宮收縮特性是由英國藥理學家亨利·哈利特·戴爾於1906年發現。[9]其噴乳特性則分別由艾薩克．奧特 (Isaac Ott)和約翰．C．史考特 (John C. Scott)兩位美國生理學家在1910年，[52]以及愛德華．艾伯特．謝菲爾和沃爾特．萊斯利．麥肯齊 (Walter Leslie Mackenzie)兩位英國生理學家在1911年提出描述。[53]

催產素是第一種被測序[54]（並合成[[55][56]）的多肽激素。美國生化學家文森特·迪維尼奧因這項工作而於1955年獲得諾貝爾化學獎。[57]

詞源

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"oxytocin"一字源於"催產藥"（oxytocic）。它來自希臘語的ὀξύς（oxys）和τόκος（tokos），意為"快速分娩"。

社會與文化

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假藥

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在非洲和亞洲國家，部分催產素產品被發現是假藥。[58][59]

其他用途

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催產素所具備的促發信任特性，可能對患有社交焦慮與憂鬱、[60]廣泛性焦慮疾患、創傷後壓力症候群和社交焦慮症等焦慮、恐懼及社交功能障礙，以及自閉症類群障礙與思覺失調症等疾病的患者有所幫助。[61][62]然而一項於2013年發表的統合分析，指出僅對自閉症類群障礙具有顯著的綜合效應。[63]一項於2022年發表的研究報告，提出在3至5歲的自閉症兒童中出現有效的跡象，但在5至12歲的兒童中則無。[64]

使用催產素的人，對於正向社交線索的辨識能力優於威脅性社交線索，[65][66]並且對恐懼的辨識能力也有所提升。[67]

  • 自閉症群類障礙:催產素可能在此障礙中扮演一定角色，並可能成為治療其重複性（減少重複性行為）與親和行為（增強其社交連結能力）的有效方法。[68]
  • 伴侶諮商：有建議將催產素用於伴侶諮商中以促進幸福感。[69]
  • 創傷後壓力症候群：有建議認為催產素在治療此症候群方面，可能比MDMA（亞甲二氧甲基苯丙胺，一種精神藥物）更安全，但催產素的療效證據較少。[70]

參見

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參考文獻

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  5. ^5.05.1Huffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, Ijzendoorn MH. Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration. Neuro Endocrinology Letters. 2012,33 (1): 21–25.PMID 22467107. 
  6. ^6.06.16.26.36.4Oxytocin. The American Society of Health-System Pharmacists. [2015-06-01]. （原始内容存档于2015-05-20）. 
  7. ^The Oxford Handbook of Prosocial Behavior. Oxford University Press. 2015: 354.ISBN 978-0-19-539981-3. （原始内容存档于2017-08-01）. 
  8. ^Hurlemann R, Grinevich V.Behavioral Pharmacology of Neuropeptides: Oxytocin. Springer. 2018: 37.ISBN 978-3-319-63739-6（英语）. 
  9. ^9.09.1Dale HH.On some physiological actions of ergot. The Journal of Physiology. May 1906,34 (3): 163–206.PMC 1465771 可免费查阅.PMID 16992821.doi:10.1113/jphysiol.1906.sp001148. 
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  16. ^16.016.116.2Pitocin (drug label for professionals). Rx List. WebMD. [2010-09-09]. （原始内容存档于2011-04-15）. 
  17. ^17.017.117.217.3Osilla EV, Patel P, Sharma S.Oxytocin. StatPearls [Internet]. StatPearls Publishing. 2025-02-15 [2025-04-19].PMID 29939625（英语）. 
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