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氯米帕明

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氯米帕明
Skeletal formula of clomipramine
Ball-and-stick model of the clomipramine molecule
臨床資料
商品名英语Drug nomenclatureAnafranil、Clomicalm及其他
其他名稱Clomipramine; 3-Chloroimipramine; G-34586[1]
AHFS/Drugs.comMonograph
MedlinePlusa697002
核准狀況
懷孕分級
  • : C
给药途径口服給藥, 靜脈注射[2]
ATC碼
法律規範狀態
法律規範
藥物動力學數據
生物利用度~50%[5]
血漿蛋白結合率96–98%[5]
药物代谢肝臟 (CYP2D6)[5]
代謝產物諾克羅米普拉明英语Desmethylclomipramine[5]
生物半衰期CMI: 19–37小時[5]
DCMI: 54–77小時[5]
排泄途徑臟 (51–60%)[5]
糞便 (24–32%)[5]
识别信息
  • 3-(3-Chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine
CAS号303-49-1  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.005.587 編輯維基數據鏈接
化学信息
化学式C19H23ClN2
摩尔质量314.86 g·mol−1
3D模型(JSmol英语JSmol
  • CN(C)CCCN1c2ccccc2CCc2ccc(Cl)cc21
  • InChI=1S/C19H23ClN2/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3 checkY
  • Key:GDLIGKIOYRNHDA-UHFFFAOYSA-N checkY

氯米帕明INN:clomipramine),商品名有 Anafranil等,是一種三環類抗憂鬱藥 (TCA)[7]。本品可用於治療強迫症(OCD)、聽覺過敏恐慌症嚴重憂鬱疾患拔毛癖[8]軀體變形障礙[9][10][11]慢性疼痛[7]外,它還在治療早洩[7]和伴隨發作性睡病猝倒發作英语cataplexy方面有良好效果[12][13]。65歲以上年長者用藥可能會降低自殺風險[7]

此外,此藥物還可改善猝倒發作之外的某些與發作性睡病相關的基本特徵(尤其是入睡前幻覺和醒前幻覺)[14]。然而這方面的證據較為薄弱。雖然它在治療上有效,但必須注意特別是在治療初期,藥物可能會增加尤其是在25歲以下年輕用藥者的自殺風險,此點與其他抗抑鬱藥(尤其是選擇性5-羥色胺再攝取抑制劑(SSRI))一樣[7]

給藥方式通常是採口服,但有時也會使用靜脈注射製劑[15][16]

用藥後常見的副作用有口乾、便秘、食慾不振、嗜睡、體重增加、性功能障礙和排尿困難[7]。嚴重副作用有25歲以下族群自殺風險升高、癲癇發作躁狂症肝臟問題[7]。如果用藥者突然停藥,可能會出現頭痛、盜汗和頭暈藥物戒斷症狀[7]。目前尚不清楚個體在懷孕期間使用對於胎兒的安全性[7]。藥物的作用機制尚未被充分了解,但被認為與血清素正腎上腺素水平升高有關聯[7]

氯米帕明於1964年由瑞士製藥公司Ciba-Geigy(之後與其他藥廠合併成為諾華製藥)發現,[17]且已列入世界衛生組織基本藥物清單之中[18]。市面上有其通用名藥物流通[7]

醫療用途

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氯米帕明有多種醫學用途,包括(但不限於)治療以下疾病:

研究顯示氯米帕明在治療強迫症方面比氟西汀氟伏沙明舍曲林等SSRI更為有效[26][27][28]。然而,由於氯米帕明有較高的副作用,因此SSRI通常在臨床中會被優先考慮。

禁忌症

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使用氯米帕明的禁忌症有:[29]

懷孕和哺乳

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個體於懷孕期間使用氯米帕明與新生兒出現先天性心臟缺陷有關聯[30][31]。它還與新生兒的可逆性戒斷反應有關聯[32]。氯米帕明也會進入母乳,因此建議母親在服用此藥物期間不要哺乳[20]

副作用

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氯米帕明可能會引起以下(但不限於)副作用:[19][20][33][29]

很常見 (頻率 > 10%):
常見 (頻率 1-10%):
不常見(0.1–1%)
很罕見 (頻率 < 0.01%):

戒斷症狀

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在逐漸或突然停用三環類抗憂鬱藥時可能會出現戒斷症狀。症狀包括:噁心、嘔吐腹痛腹瀉失眠、頭痛、緊張、焦慮、頭暈和精神狀態惡化[33]。能將原始精神疾病的復發和氯米帕明戒斷症狀區分因而很重要[34]。氯米帕明戒斷症狀可能會很嚴重[35]

抗膽鹼劑(如阿托品苯托品英语benztropine對於治療某些氯米帕明戒斷症狀可能有效[36]

藥物過量

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過量攝取氯米帕明通常會出現以下症狀:[19][33][29]

  • 中樞神經系統受抑制: 如昏迷、呼吸抑制、驚厥、昏迷。
  • 血清素症候群
  • 心血管系統影響

目前尚無氯米帕明過量的特異性解毒劑,所有治療均為支持性及症狀治療[33]

藥物交互作用

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氯米帕明可能會與許多不同的藥物相互作用,包括單胺氧化酶抑制劑、抗心律不整藥奎尼丁利尿劑、選擇性血清素再攝取抑制劑、血清素作用藥物及其他三環類抗抑鬱藥等。

氟伏沙明會增強氯米帕明的血清素能作用,同樣的,氯米帕明也會增加氟伏沙明的血藥濃度[37]

藥理學

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藥效學

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氯米帕明是一種血清素和正腎上腺素再攝取抑制劑(SNRI)。

血清素能活性

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氯米帕明是一種極強的血清素再攝取抑制劑[38][39]

強迫症

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氯米帕明是第一種受到研究,治療強迫症方面能發揮作用的藥物[17][40]

藥物動力學

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口服氯米帕明的生物利用度約為50%[19]。口服後,藥物血漿峰值濃度約在2-6小時(平均4.7小時)達到,範圍在56-154奈克/毫升(178-489奈摩爾/升)[19]

雖然氯米帕明的正常最大推薦總日劑量為250毫克,但治療抗性憂鬱症[41]和強迫症可能需用到255至300毫克範圍內的劑量。事實上,每天使用375毫克劑量,有時與文拉法辛[42]阿立哌唑聯合使用,不僅有必要,而且人體相對耐受性良好。

化學

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氯米帕明是一種三環英语tricyclic化合物,特別是一種二苯並氮雜卓,其化學結構中具有三個和一個側鏈[43]。其他二苯並氮雜卓類三環類抗憂鬱藥有丙咪嗪去甲丙咪嗪英语desipramine三咪嗪英语trimipramine[43]

歷史

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氯米帕明是由Ciba-Geigy公司開發的丙咪嗪的氯化衍生物[17][44]。於1961年首次有文獻提出,並於1963年取得專利[44]。此藥物於1970年首次在歐洲獲准用於治療憂鬱症,[44]是最後上市的一種主要三環類抗憂鬱藥[5]。事實上氯米帕明最初被FDA認為是一種"類似藥物英语me-too drug",因此未予批准用於治療憂鬱症的申請[5]。 時至今日,此藥物仍是唯一未經批准用於治療抑鬱症的三環類抗抑鬱藥,而此藥物實際上是一種高效的抗抑鬱藥[45][46]。氯米帕明最終於1989年在美國獲准用於治療強迫症,並於1990年上市[47][17]

氯米帕明多年來一直是治療強迫症的最常用治療方式,直到選擇性血清素再攝取抑制劑(SSRI)被引入,由於SSRI耐受性和安全性大幅提高(但有效性並非最好),氯米帕明在很大程度上已被SSRI取代[48][49]。氯米帕明是唯一被證明對治療強迫症有效,且經FDA批准使用的三環類抗憂鬱藥(TCA)。其他TCA在治療強迫症的臨床試驗中均未成功,可能是由於血清素能活性不足的緣故[50][51]

社會與文化

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通用名稱

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clomipramine是此藥物的英文和法文通用名稱,也是國際非專有藥名(INN)、英國核准名稱英语British Approved Name(BAN) 和法國核准名稱英语Dénomination Commune Française(DCF},而clomipramine hydrochloride(鹽酸氯米帕明)是其美國採用名稱(USAN)、美國藥典、英國核准名稱和日本核准名稱英语Japanese Accepted Name(JAN)的通用名稱[1][52][53][54]。Clomipramina是其西班牙語、葡萄牙語和義大利語的通用名稱,而clomipramin是其德語通用名稱,clomipraminum是其拉丁語通用名稱[52][54]

品牌名稱

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氯米帕明在全球主要以Anafranil和Clomicalm的商品名稱銷售,前者為人用藥物,後者為動物用藥[52][54]

獸醫用途

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氯米帕明在美國僅被許可用於治療犬類的分離焦慮,商品名稱為Clomicalm[55]。此藥物已被證明可有效治療貓和狗的強迫症[56][57]。它也顯示出與氟西汀相似的治療犬類尾部追逐英语tail chasing症狀的功效[58]。一些證據顯示它對治療犬類的噪音恐懼症有效[59]

氯米帕明也被證明對治療貓咪的尿液噴灑(標示領域 (動物)行為)有效[60]。一項為期四週的試驗顯示它可將此種行為減少高達75%的程度[61]

參考文獻

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