麦角新碱 | 60-79-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 麦角林及其衍生物
• 中文名称: 麦角新碱
• 中文别名: 爱谷米特邻碱；麦角袂春；爱各米特令碱
• 英文名称: ergometrine
• 英文别名: Ergonovine；β-ethanolamide；(6aR,9R)-N-[(2S)-1-hydroxypropan-2-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
• CAS: 60-79-7
• 化学式: C₁₉H₂₃N₃O₂
• 分子量: 325.411
• InChiKey: WVVSZNPYNCNODU-XTQGRXLLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  68.4
• 氢给体数：
  3
• 氢受体数：
  3

ADMET

代谢

肝脏的。

Hepatic.

来源:DrugBank

代谢

肝脏的。 消除途径：认为是通过非肾脏机制消除（即肝代谢，粪便排泄） 半衰期：t_1/2α=10分钟；t_1/2β=2小时

Hepatic. Route of Elimination: Thought to be eliminated by non-renal mechanisms (i.e. hepatic metabolism, excretion in feces) Half Life: t_{1/2 α}=10 minutes; t_{1/2 β}=2 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

麦角生物碱倾向于作为一个整体发挥作用，在肾上腺素能、多巴胺能和血清素能受体上产生复杂且多变的部分激动或拮抗作用。与这些效果相关的变量受到药剂、剂量、物种、组织、生理和内分泌状态以及实验条件的影响。特别是，麦角生物碱已被证明对5-HT1和5-HT2血清素受体、D1和D2多巴胺受体以及α-肾上腺素受体具有显著的亲和力。这可能导致多种不同的效果，包括血管收缩、惊厥和幻觉。麦角新碱也被知道具有非受体特异性的催产素活性。（A2914, A2915, A2916）

Ergoline alkaloids tend to act as a group, producing complex and variable effects of partial agonism or antagonism at adrenergic, dopaminergic, and serotonergic receptors. Variables relating to these effects are influenced by the agent, dosage, species, tissue, physiological, and endocrinological state, and experimental conditions. In particular, ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. Ergometrine is also known to have a non-receptor specific oxytocic activity. (A2914, A2915, A2916)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

摄入麦角生物碱已知会导致麦角中毒。麦角中毒分为两种形式，坏疽型和惊厥型，可能取决于存在的麦角生物碱的不同种类和数量。

Ingestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (A2913)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用概述：分娩后立即使用麦角新碱会降低血清基础催乳素水平，可能会减少吸吮引起的催乳素增加。它似乎也降低了母乳喂养的比率。对于希望哺乳的母亲来说，最好避免使用麦角新碱，而应依靠吸吮引起的催产素释放来加速子宫复旧。已建立哺乳的母亲催乳素水平可能不会影响她的哺乳能力。 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 对泌乳和母乳的影响：在一项研究中，12名非哺乳妇女在分娩后第3天口服单剂量的麦角新碱酒石酸盐0.2毫克，在给药后0.5至2.5小时内平均血清催乳素水平下降了10至20%。作者表示担忧，重复剂量的麦角新碱可能会抑制泌乳。[1] 从分娩后第1天到第7天，每天3次给予麦角新碱0.2毫克的10名妇女与未接受药物的6名妇女进行比较。这些妇女都没有给她们的婴儿哺乳。到分娩后第2天，接受治疗的妇女的血清催乳素水平显著降低，并在研究的7天内持续降低。在接受治疗的10名妇女中，有7人乳房充血并乳汁排出，3人泌乳逐渐受到抑制。另外两名哺乳婴儿的妇女单次静脉注射0.2毫克麦角新碱后，吸吮引起的血清催乳素反应减弱。[2] 在一项非随机研究中，11名正常分娩的妇女被肌肉注射催产素5单位加麦角新碱0.5毫克（n = 5）或单独5单位催产素（n = 6）。给予麦角新碱的妇女在0.5至2.5小时内的血清催乳素水平较低。[3] 在一项随机但非盲法的对照试验中，被认为产后出血风险低的妇女在婴儿出生后给予静脉注射麦角新碱0.5毫克（n = 197）或不给予药物（n = 135）。在分娩后48至72小时内获得的血清催乳素水平在两组之间没有差异，但在分娩后4周仍在哺乳的人中，接受麦角新碱的人比未接受的人少。[4] 在一项回顾性研究中，对威尔士18,165名分娩母亲的产科记录进行了回顾，发现第三产程中使用静脉或肌肉注射麦角新碱作为子宫收缩剂，减少了母亲在分娩后48小时哺乳的几率。在整体样本中，几率减少了36%，对于初产妇减少了49%。[5]

◉ Summary of Use during Lactation:Ergonovine given in the immediate postpartum period lowers serum basal prolactin and possibly suckling-induced prolactin increases. It also appears to decrease the rate of breastfeeding. Ergonovine is probably best avoided in mothers who wish to nurse, relying instead on suckling-induced oxytocin release to hasten uterine involution. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:In one study, a single oral dose of ergonovine maleate 0.2 mg in 12 nonbreastfeeding women on day 3 postpartum caused a 10 to 20% drop in average serum prolactin levels between 0.5 and 2.5 hours after the dose. The authors expressed concern that repeated doses of ergonovine could suppress lactation.[1] Ten women who were given ergonovine 0.2 mg 3 times daily from day 1 to 7 postpartum were compared to 6 women who did not receive the drug. None of the women breastfed their infants. Serum prolactin levels were significantly lower in the treated women by day 2 postpartum and persisted through the 7 days of the study. Seven of the 10 treated women developed breast engorgement and had milk letdown and 3 had progressive inhibition of lactation. In 2 additional women who were nursing their infants, a single dose of 0.2 mg of ergonovine intravenously blunted the response of serum prolactin to suckling.[2] In a nonrandomized study, 11 women with normal deliveries were given an intramuscular injection of either oxytocin 5 units plus ergonovine 0.5 mg (n = 5) or 5 units of oxytocin alone (n = 6). Serum prolactin levels were lower in the women given ergonovine from 0.5 to 2.5 hours.[3] In a randomized, but nonblinded, controlled trial, women thought to be at low risk of postpartum hemorrhage were given either ergonovine 0.5 mg intravenously following birth of the infant (n = 197) or no drug (n = 135). Serum prolactin levels obtained in the period of 48 to 72 hours postpartum did not differ between the groups, but fewer of those who received ergonovine were still breastfeeding at 4 weeks postpartum than those who did not.[4] In a randomized, but nonblinded, controlled trial, women thought to be at low risk of postpartum hemorrhage were given either ergonovine 0.5 mg intravenously following birth of the infant (n = 197) or no drug (n = 135). Serum prolactin levels obtained in the period of 48 to 72 hours postpartum did not differ between the groups, but fewer of those who received ergonovine were still breastfeeding at 4 weeks postpartum than those who did not.[4] A retrospective review of obstetrical records of 18,165 records of mothers giving birth in Wales found that use of intravenous or intramuscular ergonovine during the third stage of labor as a uterotonic reduced the odds of the mother breastfeeding at 48 hours postpartum. The reduction was 36% in the overall sample and 49% for primiparous mothers.[5]

来源:Drugs and Lactation Database (LactMed)

毒理性

• 暴露途径

口服、皮肤、吸入和 parenteral（污染药物）。 (A3101) 口服或肌肉注射后吸收迅速而完全。

Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101) Absorption is rapid and complete after oral or intramuscular administration.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

经口服或肌肉注射后，吸收迅速且完全。

Absorption is rapid and complete after oral or intramuscular administration.

来源:DrugBank

吸收、分配和排泄

• 消除途径

被认为是通过非肾脏机制（即肝代谢，粪便排泄）消除的

Thought to be eliminated by non-renal mechanisms (i.e. hepatic metabolism, excretion in feces)

来源:DrugBank

吸收、分配和排泄

酒石酸麦角新碱和甲基酒石酸麦角新碱口服或肌内注射后可迅速吸收。

Ergonovine maleate and methylergonovine maleate are rapidly absorbed after oral or im administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

子宫收缩通常在口服给药后5-15分钟内开始，肌内注射后2-5分钟内开始，以及静脉注射麦角新碱或甲基麦角新碱后立即开始。口服或肌内注射后子宫收缩持续3小时或更长时间，静脉注射任一药物后子宫收缩持续45分钟。

Uterine contractions are usually initiated within 5-15 minutes following oral administration, within 2-5 minutes after im injection, and immediately following iv injection of ergonovine or methylergonovine. Uterine contractions persist for 3 hours or longer after oral or im administration and for 45 minutes after iv injection of either drug.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

关于麦角胺或甲基麦角胺的消除知之甚少。有人建议这些药物主要通过非肾脏机制消除（即，在肝脏中代谢，通过粪便排出）。

Little is known about the elimination of ergonovine or methylergonovine. It has been suggested that the drugs are principally eliminated by nonrenal mechanisms (i.e., metabolism in the liver, excretion in feces).

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  麦角新碱 在 甲醇 、 potassium hydroxide 作用下， 反应 2.0h， 以45.2 g的产率得到麦角酸
  参考文献：
  名称：

  一种水解制备麦角酸的新方法

  摘要：

  本发明公开了一种麦角酸的制备方法，具体包括将麦角新碱或麦角异新碱用金属氢氧化物直接水解为麦角酸。本发明所提供的方法安全、经济，适合工业化生产，所得麦角酸纯度高。特别是采用金属氢氧化物加热条件下水解麦角新碱或麦角异新碱，对原料的纯度要求低，有利于大规模生产，降低原料提取和纯化成本。

  公开号：

  CN106565710A
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 三氧化硫 、 N,N-二甲基甲酰胺 作用下， 生成 麦角新碱
  参考文献：
  名称：

  Synthesis of Amides of Lysergic Acid¹

  摘要：

  DOI：

  10.1021/jo01085a024

文献信息

• [EN] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169567A1

  公开（公告）日：2013-11-14

  The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及螺内酰胺类似物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• [EN] IMIDAZOLINONE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'IMIDAZOLINONE EN TANT QU'ANTAGONISTES DE RÉCEPTEURS CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2010077752A1

  公开（公告）日：2010-07-08

  The present invention is directed to imidazolinone derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及嘧啶啉酮衍生物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• [EN] SUBSTITUTED PYRAZINONE COMPOUNDS FOR THE TREATMENT OF INFLAMMATION<br/>[FR] COMPOSES DE PYRAZINONE SUBSTITUES POUR LE TRAITEMENT DE L'INFLAMMATION
  申请人：PHARMACIA CORP

  公开号：WO2005035527A1

  公开（公告）日：2005-04-21

  Kinase inhibitors of Formula (I): wherein X, Ra, Rb, Rc, and Rd are as defined herein, are disclosed.

  Formula (I)的激酶抑制剂：其中X、Ra、Rb、Rc和Rd如本文所定义的那样。
• Robust Kalman filtering for continuous-time systems with norm-bounded nonlinear uncertainties
  作者：P. Shi、Y. Kaya

  DOI：10.1093/imamci/17.4.363

  日期：2000.12.1

  In this paper we study the problem of robust Kalman filtering for a class of uncertain linear continuous-time systems. The system under consideration is subjected to time-varying, norm-bounded, nonlinear parameter uncertainties in state and measurement equations. Stability of the above system is analyzed. A state estimator is designed such that the covariance of the estimation error is guaranteed to be within a certain bound for all admissible uncertainties, which is in terms of solutions of two algebraic Riccati equations.

  本文研究了一类不确定线性连续时间系统的稳健卡尔曼滤波问题。所考虑的系统在状态和测量方程中受到时变、范数有界的非线性参数不确定性的影响。对上述系统的稳定性进行了分析。设计了一种状态估计器，使得对于所有可容许的不确定性，估计误差的协方差保持在某个界限之内，这涉及到两个代数Riccati方程的解。
• 一种麦角新碱的制备方法
  申请人：成都倍特药业有限公司

  公开号：CN106397429B

  公开（公告）日：2018-12-25

  本发明具体提供了利用发酵废料制备外消旋麦角酸的方法，它包括如下操作步骤：(1)取麦角菌发酵后的废料，强碱存在条件下，在醇类溶剂中发生水解反应；(2)水解反应产物除去醇类溶剂后，酸化至pH＝3.5～4.0，析出的固形物1用甲醇和氨水混合液提取；(3)提取液除去溶剂，所得固形物2依次用水、C1～C5醇类溶剂打浆，即得外消旋麦角酸。本发明还提供了利用发酵废料制备麦角新碱的方法。本发明方法简单、没有复杂的拆分过程、反应易操作易放大生产、成本低廉、实现了废料再利用，制备出的麦角新碱仅仅经过打浆纯化后光学纯度就在98％以上，适合工业化生产。