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维基百科

米氮平

一月 02, 2023

米氮平（英語：Mirtazapine），商品名为樂活憂（港台）/瑞美隆（中国大陆）（Remeron）[6]，是一种去甲肾上腺素和特异性5-羟色胺能抗抑郁药 (NaSSA) [2] ，主要用来治疗抑郁症。米氮平也经常被用作抗焦虑药、安眠药、止吐药和食欲促进剂。若按分子结构分类，米氮平被分类为四环类抗抑郁药(TeCA) ，并且为米安舍林的6-氮杂类似物。[6] 米氮平也是一种外消旋混合物，包含(R)- 和 (S)-异构体。[6]

米氮平
臨床資料
商品名（英语：Drug nomenclature）瑞美隆（中国大陆）/樂活憂（港台）（Remeron）
其他名稱6-Azamianserin, Org 3770
AHFS（英语：American Society of Health-System Pharmacists）/Drugs.comMonograph
MedlinePlusa697009
核准狀況
  • 美 FDA: Mirtazapine
懷孕分級
给药途径口服
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%[1][2][3][4]
血漿蛋白結合率85%[1][2][3][4]
药物代谢肝脏 (CYP1A2, CYP2D6 和 CYP3A4)[1][2][3][4][5]
生物半衰期20–40小时[1][2][3][4]
排泄途徑尿液 (75%)[1]
粪便 (15%)[1][2][3][4]
识别信息
CAS号61337-67-5  
PubChem CID
  • 4205
IUPHAR/BPS
  • 7241
DrugBank
  • DB00370 
ChemSpider
  • 4060 
UNII
  • A051Q2099Q
KEGG
  • D00563 
ChEBI
  • CHEBI:6950 N
ChEMBL
  • ChEMBL654 
CompTox Dashboard (EPA)
  • DTXSID0023325
ECHA InfoCard100.080.027
化学信息
化学式C17H19N3
摩尔质量265.35 g/mol
3D模型（JSmol）
  • 交互式图像
密度1.22 g/cm3
熔点114至116 °C（237至241 °F）
沸点432 °C（810 °F）
水溶性溶于甲醇和氯仿 mg/mL (20 °C)

医疗用途

已批准的和适应症外使用

米氮平主要用来治疗重度抑郁症和其他精神障碍。[7][8]

然而研究发现，米氮平对以下症状也有一定疗效，所以米氮平有时候也会被以适应症外使用的形式处方给以下症状的治疗：

研究性的

有过文献报道的使用米氮平进行过实验性治疗的症状包括:

有效性和耐受性

2010年，NICE发布了治疗抑郁症的指南，其中包括对抗抑郁药的综述。它建议将通用SSRIs作为第一线选择，因为它们“与其他抗抑郁药同样有效并且具有有利的风险-效益比”。[40]关于米氮平，它发现：“米氮平与其他抗抑郁药在任何疗效指标上没有差异，尽管在达到缓解方面，米氮平似乎具有统计学但不具有临床意义的优势。此外，米氮平具有优于SSRIs的统计学优势。就减少抑郁症状而言，这种差异在临床上并不重要。然而，有强有力的证据表明服用米氮平的患者由于副作用而不太可能提早离开治疗，尽管对于报告副作用的患者不是这种情况或因任何原因提早离开治疗。“[41]]

2011年Cochrane评价将米氮平与其他抗抑郁药进行了比较，结果发现，虽然它对患者的起效较快（在第2周时），但在第6周时它与其他的抗抑郁药大致相同。[42]

一项针对抗抑郁药和睡眠的2012年评论发现，在许多因抑郁引起睡眠障碍的患者中，米氮平减少了入睡所需的时间并提高了睡眠质量，但在某些人中，它会扰乱睡眠，有8％至28％的人会有不安腿综合征，并且它在极少数情况下导致REM睡眠行为障碍。

2018年有项系统评价和网络荟萃分析比较了12种抗抑郁药物的疗效和耐受性，结果显示米氮平是头对头研究中最有效的抗抑郁药之一。[43]

在第1周之后，相较于SSRI，米氮平有着更快的起效时间。[44][45]

副作用

2011年Cochrane评价发现，与其他抗抑郁药相比，它更容易引起体重增加和嗜睡，但它比三环类抗抑郁药引起震颤的可能性更小，并且比SSRIs更不可能引起恶心和性功能障碍。[42]

米氮平不被认为存在很多副作用的风险，这些副作用通常和其他抗抑郁药，例如SSRI，有关，并且当他们一起使用时可以改善某些副作用。这些不良反应包括食欲减退，体重减轻，失眠，恶心和呕吐，腹泻，尿潴留，体温升高，出汗过多，瞳孔扩张和性功能障碍。[46][47]

一般地，有些抗抑郁药，例如SSRI，会自相矛盾地加剧一些人的抑郁或焦虑或自杀意念。[48]尽管米氮平具有镇静作用，但据信也有能力做到这一点，所以在美国和其他一些国家，它带有黑框标签来警告这些潜在的影响。

2000年发表的一份病例报告指出，米氮平可以抵消可乐定的作用，导致血压升高。[49]

不良反应发生率[50]

非常常见（≥1/10）

  • 体重增加
  • 食欲增加
  • 嗜睡
  • 镇静作用
  • 口干

常见（≥1/100~＜1/10）

  • 梦异常
  • 意思混乱
  • 焦虑
  • 失眠

不常见（≥1,000~<1/100）

罕见（≥1/10,000~>1/1,000）

  • 肌痉挛
  • 血清氨基转移酶增加

频率不详

停药

米氮平和其他抗抑郁药可能在停止服用后引发停药综合征。[46][51][52]建议逐渐缓慢减少剂量，以尽量减少停药综合征。[53]突然停止米氮平治疗的后果可能包括抑郁，焦虑，耳鸣，惊恐发作，眩晕，精神运动激动，易怒，食欲减退，失眠，腹泻，恶心，呕吐，流感类似过敏和瘙痒症，头痛，有时会有轻度躁狂或躁狂症。[51][54][55][56][57]

药物相互作用

与细胞色素（CYP）P450同工酶CYP1A2，CYP2D6和/或CYP3A4的抑制剂或诱导剂同时使用可导致米氮平的浓度改变，因为这些是负责其代谢的主要酶。[58][59]例如，已知氟西汀和帕罗西汀（这些酶的抑制剂）适度增加米氮平水平，而卡马西平（一种诱导剂）可显著降低米氮平水平。[58]据报道，在肝功能损害和中度肾功能损害的人群中，米氮平口服清除率降低约30％；而严重肾功能损害患者的口服清除率减少50％。[58]

根据制造商提供的信息，米氮平不应在任何单胺氧化酶抑制剂（MAOI）停用后两周内开始使用；同样，MAOI不应在停用米氮平后两周内给药。[60]米氮平与SSRI，SNRI或TCA联合作为增强策略被认为是相对安全的，而且通常用于治疗。[61]文拉法辛和米氮平的组合，有时被称为“加州火箭燃料”。[62][63]已知在氟西汀和米氮平同时给药的情况下可能发生5-羟色胺综合征。

过量

如果服用过量，米氮平被认为是相对安全的[45]，尽管过量服用的毒性比大多数SSRIs（西酞普兰除外）略高。[64]与三环类抗抑郁药不同，米氮平在最大推荐剂量的7至22倍时未显示出明显的心血管不良反应。[65]与三环类抗抑郁药相比，过量服用标准剂量30至50倍的病例报告称药物相对无毒。[66][67]

据报道，有12人死于米氮平过量。[68][69]米氮平的致命毒性指数（每百万处方死亡人数）为3.1（95％CI：0.1至17.2）。这类似于用SSRIs观察到的情况。[70]

药理学

药效学

参见：抗抑郁药和四环类抗抑郁药
米氮平[71]
Ki(nm) 物种 来源 参考
SERT >10,000 人类 [72][73]
NET ≥4,600 人类 [74][72]
DAT >10,000 人类 [75][76]
5-HT1A 3,330~5,010 人类 [46][76]
5-HT1B 3,534~12,600 人类 [46][73]
5-HT1D 794-5,010 人类 [46][73]
5-HT1E 728 人类 [73]
5-HT1F 583 人类 [73]
5-HT2A 6.3~69 人类 [46][73][77]
5-HT2B 200 人类 [46]
5-HT2C 8.9~39 人类 [46][73][77]
5-HT3 7.9 人类 [46]
5-HT4L >10,000 人类 [73]
5-HT5A 670 人类 [73]
5-HT6 ND ND ND
5-HT7 265 人类 [73][77]
α1A 316~1,815 人类 [73]
α2A 20 人类 [73][77]
α2B 88 人类 [73]
α2C 18 人类 [73][77]
β >10,000 人类 [73]
D1 ~4167 大鼠 [77]
D2 >5,454 人类 [73][77]
D3 5723 人类 [73][77]
D4 2,518 人类 [73]
H1 0.14~1.6 人类 [46][73][77][78]
H2 >10,000 大鼠 [78][79]
H3 83,200 人类 [79]
H4 >100,000 人类 [79]
mAch 670 人类 [46][74]
VGSC 6,905 大鼠 [73]
VDCC >10,000 大鼠 [73]

米氮平有时被分类为去甲肾上腺素和特异性五羟色胺能能抗抑郁药（NaSSA），[46]尽管支持此分类的证据并不可靠。[80]米氮平有抗去甲肾上腺素、组胺和5-羟色胺受体的功效。[81][46]它特别是肾上腺素α 2A ，α2B，和α2C受体、组胺H1受体和5-羟色胺5-HT2A、5-HT2C和5-HT3的拮抗剂或反向激动剂。[46][81]不同于许多其他的抗抑郁药，它不抑制5-羟色胺、去甲肾上腺素或多巴胺的再摄取，也不抑制单胺氧化酶。[82]同多数抗抑郁药类似，米氮平的抗胆碱能、阻断钠离子通道或阻断钙离子通道的效应很弱甚至没有。然而在过量食用时，米氮平具有更好的耐受性和低毒性。米氮平是TCA或TeCA中最有效的H1受体拮抗剂，拮抗H1受体是米氮平最强的活性，它在低剂量下为选择性H1受体拮抗剂。[46][73]

米氮平的(S)-(+)对映体负责5-羟色胺5-HT2A和5-HT2C的拮抗作用，[6](R)-(-)对映体负责对5-HT3受体的拮抗作用。虽然(R)-(-)是很强的组胺H1受体的拮抗剂，两种对映体都参与了对组胺H1受体和肾上腺素α2受体的拮抗作用。

虽然没有临床意义，已经发现米氮平在高浓度的情况下是κ阿片样受体的部分激动剂[83]（EC50=7.2nm）。

α2肾上腺素受体

作为肾上腺素α2受体的拮抗剂，其功能主要是由于抑制自受体和异受体，提高去甲肾上腺素和5-羟色胺能的神经传递，特别是中央 5-HT1A受体介导的中缝背核和海马的神经递质的传导；因此，米氮平的分类为NaSSA。间接地增强α1受体介导的5-羟色胺细胞放电和抑制、直接阻断5-羟色胺神经元上的异受体会增加细胞外5-羟色胺的浓度。[46][7][84][85][86]因此，米氮平被认为是5-HT1A受体的“间接激动剂 ”。[85]中枢5-HT1A受体的活动增加被认为是大多数抗抑郁药物功效的主要原理。[87]

5-HT2和5-HT3受体

对5-HT2受体亚族的拮抗作用和对5-HT2C受体的反向激动作用似乎是米氮平治疗抑郁的机理之一。[88][89]米氮平能增加前额叶皮质中的多巴胺能，对大鼠的研究结果表明，阻断α2受体和5-HT2C受体能对大鼠的此区域对多巴胺的释放去抑制。[90]米氮平对5-HT2A受体的拮抗作用对焦虑、失眠和性功能有改进。[46]已证明米氮平可以降低人类和各种动物的寻药行为。它也正在被研究对物质滥用的行为，以减少戒断效应和提高缓解率。[91][92][93][94]

由于对5-HT3受体的拮抗作用，米氮平与批准的止吐药昂丹司琼有着共同的作用，它可显著改善病人的恶心、呕吐、腹泻和肠易激综合征的症状。[95]米氮平可作为一种廉价的止吐药以替代昂丹司琼。[96]在一些研究中，在一些研究中，也发现米氮平对5-HT3受体的阻断可以改善焦虑并有效治疗物质依赖。与物质滥用咨询相结合，米氮平成功地减少了对冰毒依赖的个体对冰毒的使用。[97][92][93][94]与米氮平相比，SSRIs，SNRIs，MAOIs和一些TCAs增加了5-HT2A，5-HT2C和5-HT3受体的一般活性，造成负面结果和副作用，其中最突出的包括厌食、失眠和性功能障碍（丧失主动的性欲、性快感缺失）以及恶心和腹泻等等。因此，它通常与这些药物结合使用，以减少其副作用，并产生更强的抗抑郁作用。[47][98]

米氮平不具有5-羟色胺能活性，不会引起5-羟色胺能副作用或5-羟色胺综合征。[99][80]这与其不是5-羟色胺再摄取抑制剂或MAOI，也不是5-羟色胺受体激动剂的事实一致。[80][99]没有关于单独使用米氮平的5-羟色胺综合征的报道，并且未发现米氮平过量引起5-羟色胺综合征。[99][80][100]但是，有一些案例报告米氮平与SSRIs等5-羟色胺能药物联合应用引起5-羟色胺综合征，尽管这些报道非常罕见，并不一定暗示米氮平是致病因素。[80][101][102][103][104][105]在MAOI中加入米氮平不会引起5-羟色胺综合征，并被认为是一种安全的组合。[80][99]此外，米氮平实际上可用于治疗5-羟色胺综合征，至少有一篇文章发现它可有效地解决该综合征。[80][106][107]这是按照5-HT2A受体是导致5-羟色胺综合征的主要受体（而5-HT1A受体似乎是保护性的）。[80][99]米氮平是一种有效的5-HT2A受体拮抗剂，而赛庚啶是一种具有这种特性的药物，可介导5-羟色胺综合征的恢复，并且在临床上已成熟，可作为对抗它的解毒剂。[80][108]

H1受体

米氮平是一种非常强的H1受体反向激动剂，因此，它可以引起强大的镇静和催眠作用。[46]米氮平于健康志愿者的单15毫克剂量已被发现导致在H1受体的80％以上的占用并诱导强烈的嗜睡。[109]但是，经过长时间的慢性治疗，H1会脱敏，并且抗组胺能的效应变得更耐受。许多患者也可能在晚上服用以避免这种影响，这似乎是对抗它们的有效策略。阻断H1受体可以改善先前存在的患病个体的过敏、瘙痒、恶心和失眠。然而，它也可能有助于增加体重。与H1受体相反，米氮平仅对毒蕈碱乙酰胆碱受体仅具有低亲和力，尽管在临床实践中有时仍会出现口干、便秘和瞳孔散大等抗胆碱能副作用。[110]

药代动力学

米氮平的口服生物利用度约为50％。有85%结合到血浆蛋白。它主要在肝脏中通过去甲基化和细胞色素P450酶的羟基化代谢，其主要代谢物之一是去甲基米氮平。整体清除半衰期为20~40小时。约15％由粪便、75％由尿液排出。[111]

社会文化

通用名

Mirtazapine是该药物的英文、法文以及INN、USAN、USP、BAN、DCF、JAN的通用名。[112][113]它的西班牙语通用名是mirtazapina、德语通用名是Mirtazapin、拉丁语通用名是mirtazapinum。[112]

品牌名称

米氮平在全球使用相当多的商品名被出售，包括：

Adco-Mirteron、Afloyan、Amirel、Arintapin Smelt、Avanza、Azapin、Beron、Bilanz、Calixta、Ciblex、Combar、Comenter、Depreram、Divaril、Esprital、Maz、Menelat、Mepirzapine、Merdaten、Meronin、Mi Er Ning、Milivin、Minelza、Minivane、Mirastad、Mirazep、Miro、Miron、Mirrador、Mirt、Mirta、Mirtabene、Mirtadepi、Mirtagamma、Mirtagen、Mirtalan、Mirtamor、Mirtamylan、Mirtan、Mirtaneo、Mirtapax、Mirtapil、Mirtapine、Mirtaron、Mirtastad、Mirtax、Mirtaz、Mirtazap、Mirtazapin、Mirtazapina、Mirtazapine、Mirtazapinum、Mirtazelon、Mirtazon、Mirtazonal、Mirtel、Mirtimash、Mirtin、Mirtine、Mirzapine、Mirzaten、Mirzest、Mitaprex、Mitaxind、Mitocent、Mitrazin、Mizapin、Motofen、Mytra、Norset、Noxibel、Pharmataz、Promyrtil、Rapizapine、Ramure、Redepra、Reflex、Remergil、Remergon、Remeron、Remirta、Rexer、Saxib、Sinmaron、Smilon、Tazepin、Tazimed、Tetrazic、Tifona、U-Mirtaron、U-zepine、Valdren、Vastat、Velorin、Yarocen、Zania、Zapex、Zestat、Zismirt、Zispin、Zuleptan、 Zulin.

历史

米氮平在1989年的时候由Organon合成出来并被公布。首次被批准用于治疗重性抑郁障碍是在1994年的荷兰。1996年，商品名为Remeron的米氮平被引入美国。[111][114]

引用

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一月 02, 2023
米氮平, 英語, mirtazapine, 商品名为樂活憂, 港台, 瑞美隆, 中国大陆, remeron, 是一种去甲肾上腺素和特异性5, 羟色胺能抗抑郁药, nassa, 主要用来治疗抑郁症, 也经常被用作抗焦虑药, 安眠药, 止吐药和食欲促进剂, 若按分子结构分类, 被分类为四环类抗抑郁药, teca, 并且为米安舍林的6, 氮杂类似物, 也是一种外消旋混合物, 包含, 异构体, 臨床資料商品名, 英语, drug, nomenclature, 瑞美隆, 中国大陆, 樂活憂, 港台, remeron, 其他名. 米氮平 英語 Mirtazapine 商品名为樂活憂 港台 瑞美隆 中国大陆 Remeron 6 是一种去甲肾上腺素和特异性5 羟色胺能抗抑郁药 NaSSA 2 主要用来治疗抑郁症 米氮平也经常被用作抗焦虑药 安眠药 止吐药和食欲促进剂 若按分子结构分类 米氮平被分类为四环类抗抑郁药 TeCA 并且为米安舍林的6 氮杂类似物 6 米氮平也是一种外消旋混合物 包含 R 和 S 异构体 6 米氮平臨床資料商品名 英语 Drug nomenclature 瑞美隆 中国大陆 樂活憂 港台 Remeron 其他名稱6 Azamianserin Org 3770AHFS 英语 American Society of Health System Pharmacists Drugs comMonographMedlinePlusa697009核准狀況美 FDA Mirtazapine懷孕分級澳 B3给药途径口服ATC碼N06AX11 WHO 法律規範狀態法律規範澳 限医生处方 S4 加 处方药 only 英 处方药 only POM 美 处方药 only 藥物動力學數據生物利用度50 1 2 3 4 血漿蛋白結合率85 1 2 3 4 药物代谢肝脏 CYP1A2 CYP2D6 和 CYP3A4 1 2 3 4 5 生物半衰期20 40小时 1 2 3 4 排泄途徑尿液 75 1 粪便 15 1 2 3 4 识别信息IUPAC命名法 2 methyl 1 2 3 4 10 14b hexahydropyrazino 2 1 a pyrido 2 3 c 2 benzazepineCAS号61337 67 5 PubChem CID4205IUPHAR BPS7241DrugBankDB00370 ChemSpider4060 UNIIA051Q2099QKEGGD00563 ChEBICHEBI 6950 NChEMBLChEMBL654 CompTox Dashboard EPA DTXSID0023325ECHA InfoCard100 080 027化学信息化学式C 17H 19N 3摩尔质量265 35 g mol3D模型 JSmol 交互式图像密度1 22 g cm3熔点114至116 C 237至241 F 沸点432 C 810 F 水溶性溶于甲醇和氯仿 mg mL 20 C SMILES n1cccc3c1N4C c2ccccc2C3 CN C CC4InChI InChI 1S C17H19N3 c1 19 9 10 20 16 12 19 15 7 3 2 5 13 15 11 14 6 4 8 18 17 14 20 h2 8 16H 9 12H2 1H3 Key RONZAEMNMFQXRA UHFFFAOYSA N 目录 1 医疗用途 1 1 已批准的和适应症外使用 1 2 研究性的 1 3 有效性和耐受性 2 副作用 2 1 不良反应发生率 50 2 2 停药 3 药物相互作用 4 过量 5 药理学 5 1 药效学 5 1 1 a2肾上腺素受体 5 1 2 5 HT2和5 HT3受体 5 1 3 H1受体 5 2 药代动力学 6 社会文化 6 1 通用名 6 2 品牌名称 6 3 历史 7 引用医疗用途 编辑已批准的和适应症外使用 编辑 米氮平主要用来治疗重度抑郁症和其他精神障碍 7 8 然而研究发现 米氮平对以下症状也有一定疗效 所以米氮平有时候也会被以适应症外使用的形式处方给以下症状的治疗 广泛性焦虑症 5 9 社交恐惧症 10 11 强迫症 10 12 恐慌症 10 13 14 创伤后应激障碍 10 食欲不振 体重过低 15 16 17 失眠 18 19 恶心 呕吐 20 21 22 瘙痒 23 24 头痛和偏头痛 21 25 26 研究性的 编辑 有过文献报道的使用米氮平进行过实验性治疗的症状包括 睡眠呼吸暂停 低呼吸量 27 28 不适当的性行为和其他由自闭症和其他广泛性发育障碍等导致的继发症状 29 30 31 32 抗精神病药导致的静坐不能 33 34 药物戒断 药物依赖和戒毒 35 精神分裂症导致的消极 抑郁和认知障碍 作为辅助治疗 36 37 有文献报道 一例伴有视觉幻觉的帕金森氏病精神病患者在使用米氮平后症状有所减轻 38 这与近期发现的作用于5 HT2A受体的反激动剂可以有效地减轻帕金森氏病的精神病症状这个事实相吻合 39 有效性和耐受性 编辑 2010年 NICE发布了治疗抑郁症的指南 其中包括对抗抑郁药的综述 它建议将通用SSRIs作为第一线选择 因为它们 与其他抗抑郁药同样有效并且具有有利的风险 效益比 40 关于米氮平 它发现 米氮平与其他抗抑郁药在任何疗效指标上没有差异 尽管在达到缓解方面 米氮平似乎具有统计学但不具有临床意义的优势 此外 米氮平具有优于SSRIs的统计学优势 就减少抑郁症状而言 这种差异在临床上并不重要 然而 有强有力的证据表明服用米氮平的患者由于副作用而不太可能提早离开治疗 尽管对于报告副作用的患者不是这种情况或因任何原因提早离开治疗 41 2011年Cochrane评价将米氮平与其他抗抑郁药进行了比较 结果发现 虽然它对患者的起效较快 在第2周时 但在第6周时它与其他的抗抑郁药大致相同 42 一项针对抗抑郁药和睡眠的2012年评论发现 在许多因抑郁引起睡眠障碍的患者中 米氮平减少了入睡所需的时间并提高了睡眠质量 但在某些人中 它会扰乱睡眠 有8 至28 的人会有不安腿综合征 并且它在极少数情况下导致REM睡眠行为障碍 2018年有项系统评价和网络荟萃分析比较了12种抗抑郁药物的疗效和耐受性 结果显示米氮平是头对头研究中最有效的抗抑郁药之一 43 在第1周之后 相较于SSRI 米氮平有着更快的起效时间 44 45 副作用 编辑2011年Cochrane评价发现 与其他抗抑郁药相比 它更容易引起体重增加和嗜睡 但它比三环类抗抑郁药引起震颤的可能性更小 并且比SSRIs更不可能引起恶心和性功能障碍 42 米氮平不被认为存在很多副作用的风险 这些副作用通常和其他抗抑郁药 例如SSRI 有关 并且当他们一起使用时可以改善某些副作用 这些不良反应包括食欲减退 体重减轻 失眠 恶心和呕吐 腹泻 尿潴留 体温升高 出汗过多 瞳孔扩张和性功能障碍 46 47 一般地 有些抗抑郁药 例如SSRI 会自相矛盾地加剧一些人的抑郁或焦虑或自杀意念 48 尽管米氮平具有镇静作用 但据信也有能力做到这一点 所以在美国和其他一些国家 它带有黑框标签来警告这些潜在的影响 2000年发表的一份病例报告指出 米氮平可以抵消可乐定的作用 导致血压升高 49 不良反应发生率 50 编辑 非常常见 1 10 体重增加 食欲增加 嗜睡 镇静作用 口干常见 1 100 1 10 梦异常 意思混乱 焦虑 失眠不常见 1 000 lt 1 100 梦魇 躁狂症 兴奋 幻觉 精神运动性坐立不安 包括静坐不能 运动机能亢进 感觉异常 不宁腿症状 低血压 口腔感觉减退罕见 1 10 000 gt 1 1 000 肌痉挛 血清氨基转移酶增加频率不详 骨髓抑制 粒细胞减少 粒细胞缺乏 再生性贫血以及血小板减少症 嗜酸性粒细胞增多 低钠血症 自杀意图 自杀行为 惊厥 发作 5 羟色胺综合征 口腔感觉异常 口唇水肿 Stevens Johnson综合征 大疱性皮炎 多形性红斑 中毒性表皮坏死停药 编辑 米氮平和其他抗抑郁药可能在停止服用后引发停药综合征 46 51 52 建议逐渐缓慢减少剂量 以尽量减少停药综合征 53 突然停止米氮平治疗的后果可能包括抑郁 焦虑 耳鸣 惊恐发作 眩晕 精神运动激动 易怒 食欲减退 失眠 腹泻 恶心 呕吐 流感类似过敏和瘙痒症 头痛 有时会有轻度躁狂或躁狂症 51 54 55 56 57 药物相互作用 编辑与细胞色素 CYP P450同工酶CYP1A2 CYP2D6和 或CYP3A4的抑制剂或诱导剂同时使用可导致米氮平的浓度改变 因为这些是负责其代谢的主要酶 58 59 例如 已知氟西汀和帕罗西汀 这些酶的抑制剂 适度增加米氮平水平 而卡马西平 一种诱导剂 可显著降低米氮平水平 58 据报道 在肝功能损害和中度肾功能损害的人群中 米氮平口服清除率降低约30 而严重肾功能损害患者的口服清除率减少50 58 根据制造商提供的信息 米氮平不应在任何单胺氧化酶抑制剂 MAOI 停用后两周内开始使用 同样 MAOI不应在停用米氮平后两周内给药 60 米氮平与SSRI SNRI或TCA联合作为增强策略被认为是相对安全的 而且通常用于治疗 61 文拉法辛和米氮平的组合 有时被称为 加州火箭燃料 62 63 已知在氟西汀和米氮平同时给药的情况下可能发生5 羟色胺综合征 过量 编辑如果服用过量 米氮平被认为是相对安全的 45 尽管过量服用的毒性比大多数SSRIs 西酞普兰除外 略高 64 与三环类抗抑郁药不同 米氮平在最大推荐剂量的7至22倍时未显示出明显的心血管不良反应 65 与三环类抗抑郁药相比 过量服用标准剂量30至50倍的病例报告称药物相对无毒 66 67 据报道 有12人死于米氮平过量 68 69 米氮平的致命毒性指数 每百万处方死亡人数 为3 1 95 CI 0 1至17 2 这类似于用SSRIs观察到的情况 70 药理学 编辑药效学 编辑 参见 抗抑郁药和四环类抗抑郁药 米氮平 71 Ki nm 物种 来源 参考SERT gt 10 000 人类 72 73 NET 4 600 人类 74 72 DAT gt 10 000 人类 75 76 5 HT1A 3 330 5 010 人类 46 76 5 HT1B 3 534 12 600 人类 46 73 5 HT1D 794 5 010 人类 46 73 5 HT1E 728 人类 73 5 HT1F 583 人类 73 5 HT2A 6 3 69 人类 46 73 77 5 HT2B 200 人类 46 5 HT2C 8 9 39 人类 46 73 77 5 HT3 7 9 人类 46 5 HT4L gt 10 000 人类 73 5 HT5A 670 人类 73 5 HT6 ND ND ND5 HT7 265 人类 73 77 a1A 316 1 815 人类 73 a2A 20 人类 73 77 a2B 88 人类 73 a2C 18 人类 73 77 b gt 10 000 人类 73 D1 4167 大鼠 77 D2 gt 5 454 人类 73 77 D3 5723 人类 73 77 D4 2 518 人类 73 H1 0 14 1 6 人类 46 73 77 78 H2 gt 10 000 大鼠 78 79 H3 83 200 人类 79 H4 gt 100 000 人类 79 mAch 670 人类 46 74 VGSC 6 905 大鼠 73 VDCC gt 10 000 大鼠 73 米氮平有时被分类为去甲肾上腺素和特异性五羟色胺能能抗抑郁药 NaSSA 46 尽管支持此分类的证据并不可靠 80 米氮平有抗去甲肾上腺素 组胺和5 羟色胺受体的功效 81 46 它特别是肾上腺素a 2A a2B 和a2C受体 组胺H1受体和5 羟色胺5 HT2A 5 HT2C和5 HT3的拮抗剂或反向激动剂 46 81 不同于许多其他的抗抑郁药 它不抑制5 羟色胺 去甲肾上腺素或多巴胺的再摄取 也不抑制单胺氧化酶 82 同多数抗抑郁药类似 米氮平的抗胆碱能 阻断钠离子通道或阻断钙离子通道的效应很弱甚至没有 然而在过量食用时 米氮平具有更好的耐受性和低毒性 米氮平是TCA或TeCA中最有效的H1受体拮抗剂 拮抗H1受体是米氮平最强的活性 它在低剂量下为选择性H1受体拮抗剂 46 73 米氮平的 S 对映体负责5 羟色胺5 HT2A和5 HT2C的拮抗作用 6 R 对映体负责对5 HT3受体的拮抗作用 虽然 R 是很强的组胺H1受体的拮抗剂 两种对映体都参与了对组胺H1受体和肾上腺素a2受体的拮抗作用 虽然没有临床意义 已经发现米氮平在高浓度的情况下是k阿片样受体的部分激动剂 83 EC50 7 2nm a2肾上腺素受体 编辑 作为肾上腺素a2受体的拮抗剂 其功能主要是由于抑制自受体和异受体 提高去甲肾上腺素和5 羟色胺能的神经传递 特别是中央 5 HT1A受体介导的中缝背核和海马的神经递质的传导 因此 米氮平的分类为NaSSA 间接地增强a1受体介导的5 羟色胺细胞放电和抑制 直接阻断5 羟色胺神经元上的异受体会增加细胞外5 羟色胺的浓度 46 7 84 85 86 因此 米氮平被认为是5 HT1A受体的 间接激动剂 85 中枢5 HT1A受体的活动增加被认为是大多数抗抑郁药物功效的主要原理 87 5 HT2和5 HT3受体 编辑 对5 HT2受体亚族的拮抗作用和对5 HT2C受体的反向激动作用似乎是米氮平治疗抑郁的机理之一 88 89 米氮平能增加前额叶皮质中的多巴胺能 对大鼠的研究结果表明 阻断a2受体和5 HT2C受体能对大鼠的此区域对多巴胺的释放去抑制 90 米氮平对5 HT2A受体的拮抗作用对焦虑 失眠和性功能有改进 46 已证明米氮平可以降低人类和各种动物的寻药行为 它也正在被研究对物质滥用的行为 以减少戒断效应和提高缓解率 91 92 93 94 由于对5 HT3受体的拮抗作用 米氮平与批准的止吐药昂丹司琼有着共同的作用 它可显著改善病人的恶心 呕吐 腹泻和肠易激综合征的症状 95 米氮平可作为一种廉价的止吐药以替代昂丹司琼 96 在一些研究中 在一些研究中 也发现米氮平对5 HT3受体的阻断可以改善焦虑并有效治疗物质依赖 与物质滥用咨询相结合 米氮平成功地减少了对冰毒依赖的个体对冰毒的使用 97 92 93 94 与米氮平相比 SSRIs SNRIs MAOIs和一些TCAs增加了5 HT2A 5 HT2C和5 HT3受体的一般活性 造成负面结果和副作用 其中最突出的包括厌食 失眠和性功能障碍 丧失主动的性欲 性快感缺失 以及恶心和腹泻等等 因此 它通常与这些药物结合使用 以减少其副作用 并产生更强的抗抑郁作用 47 98 米氮平不具有5 羟色胺能活性 不会引起5 羟色胺能副作用或5 羟色胺综合征 99 80 这与其不是5 羟色胺再摄取抑制剂或MAOI 也不是5 羟色胺受体激动剂的事实一致 80 99 没有关于单独使用米氮平的5 羟色胺综合征的报道 并且未发现米氮平过量引起5 羟色胺综合征 99 80 100 但是 有一些案例报告米氮平与SSRIs等5 羟色胺能药物联合应用引起5 羟色胺综合征 尽管这些报道非常罕见 并不一定暗示米氮平是致病因素 80 101 102 103 104 105 在MAOI中加入米氮平不会引起5 羟色胺综合征 并被认为是一种安全的组合 80 99 此外 米氮平实际上可用于治疗5 羟色胺综合征 至少有一篇文章发现它可有效地解决该综合征 80 106 107 这是按照5 HT2A受体是导致5 羟色胺综合征的主要受体 而5 HT1A受体似乎是保护性的 80 99 米氮平是一种有效的5 HT2A受体拮抗剂 而赛庚啶是一种具有这种特性的药物 可介导5 羟色胺综合征的恢复 并且在临床上已成熟 可作为对抗它的解毒剂 80 108 H1受体 编辑 米氮平是一种非常强的H1受体反向激动剂 因此 它可以引起强大的镇静和催眠作用 46 米氮平于健康志愿者的单15毫克剂量已被发现导致在H1受体的80 以上的占用并诱导强烈的嗜睡 109 但是 经过长时间的慢性治疗 H1会脱敏 并且抗组胺能的效应变得更耐受 许多患者也可能在晚上服用以避免这种影响 这似乎是对抗它们的有效策略 阻断H1受体可以改善先前存在的患病个体的过敏 瘙痒 恶心和失眠 然而 它也可能有助于增加体重 与H1受体相反 米氮平仅对毒蕈碱乙酰胆碱受体仅具有低亲和力 尽管在临床实践中有时仍会出现口干 便秘和瞳孔散大等抗胆碱能副作用 110 药代动力学 编辑 米氮平的口服生物利用度约为50 有85 结合到血浆蛋白 它主要在肝脏中通过去甲基化和细胞色素P450酶的羟基化代谢 其主要代谢物之一是去甲基米氮平 整体清除半衰期为20 40小时 约15 由粪便 75 由尿液排出 111 社会文化 编辑通用名 编辑 Mirtazapine是该药物的英文 法文以及INN USAN USP BAN DCF JAN的通用名 112 113 它的西班牙语通用名是mirtazapina 德语通用名是Mirtazapin 拉丁语通用名是mirtazapinum 112 品牌名称 编辑 米氮平在全球使用相当多的商品名被出售 包括 Adco Mirteron Afloyan Amirel Arintapin Smelt Avanza Azapin Beron Bilanz Calixta Ciblex Combar Comenter Depreram Divaril Esprital Maz Menelat Mepirzapine Merdaten Meronin Mi Er Ning Milivin Minelza Minivane Mirastad Mirazep Miro Miron Mirrador Mirt Mirta Mirtabene Mirtadepi Mirtagamma Mirtagen Mirtalan Mirtamor Mirtamylan Mirtan Mirtaneo Mirtapax Mirtapil Mirtapine Mirtaron Mirtastad Mirtax Mirtaz Mirtazap Mirtazapin Mirtazapina Mirtazapine Mirtazapinum Mirtazelon Mirtazon Mirtazonal Mirtel Mirtimash Mirtin Mirtine Mirzapine Mirzaten Mirzest Mitaprex Mitaxind Mitocent Mitrazin Mizapin Motofen Mytra Norset Noxibel Pharmataz Promyrtil Rapizapine Ramure Redepra Reflex Remergil Remergon Remeron Remirta Rexer Saxib Sinmaron Smilon Tazepin Tazimed 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