美芬丁胺 | 100-92-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 美芬丁胺
• 中文别名: N,2-二甲基-1-苯基丙-2-胺；恢压敏
• 英文名称: mephentermine
• 英文别名: mephentermine hemisulfate；Mephentermin；(1,1-dimethyl-2-phenyl-ethyl)-methyl-amine；(1,1-Dimethyl-2-phenyl-aethyl)-methyl-amin；2-Methylamino-2-methyl-1-phenyl-propan；N,2-dimethyl-1-phenylpropan-2-amine
• CAS: 100-92-5
• 化学式: C₁₁H₁₇N
• 分子量: 163.263
• InChiKey: RXQCGGRTAILOIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

肝脏的，通过N-去甲基化然后是p-羟基化。

Hepatic, by N-demethylation and then p-hydroxylation.

来源:DrugBank

代谢

美芬特明在肝脏通过N-去甲基化和随后的对位羟基化代谢为诺美芬特明和对位羟基诺美芬特明。/硫酸盐/

MEPHENTERMINE IS METABOLIZED IN THE LIVER BY N-DEMETHYLATION & SUBSEQUENT P-HYDROXYLATION TO NORMEPHENTERMINE & P-HYDROXYNORMEPHENTERMINE. /SULFATE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

苯丙胺在体外被兔肝微粒体代谢为苯丙胺（II）、N-羟基苯丙胺（III）和N-羟基苯丙胺。代谢物（II）和（III）以及未改变的苯丙胺在给人单次给药硫酸苯丙胺后的尿液中被发现。

MEPHENTERMINE WAS METABOLIZED IN VITRO BY RABBIT LIVER MICROSOMES TO PHENTERMINE (II), N-HYDROXYMEPHENTERMINE (III), & N-HYDROXYPHENTERMINE. METABOLITES (II) & (III) PLUS UNCHANGED MEPHENTERMINE FOUND IN URINE OF HUMAN ADMIN SINGLE DOSE OF MEPHENTERMINE SULFATE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

当与大鼠肝脏微粒体和细胞溶质制剂一起培养时，美芬特明（MP）、芬特明（Ph）、对羟基-MP、对羟基-Ph、N-羟基-MP和N-羟基-Ph的代谢物通过气相色谱（glc）和气相色谱-质谱联用技术（glc mass spectrometry）被鉴定出来。代谢物的鉴定表明了以下MP的新代谢途径：MP通过NADPH依赖性微粒体形成对羟基-MP，对羟基-MP形成对羟基-Ph，以及NADH依赖性微粒体通过对羟基-Ph形成Ph。

Metabolites of mephentermine (MP), phentermine (Ph), p-hydroxy-MP, p-hydroxy-Ph, N-hydroxy-MP and N-hydroxy-Ph on incubation with rat liver microsomal and cytosolic preparations were identified by glc and glc mass spectrometry. Identification of the metabolites indicated the following new metabolic routes of MP: NADPH dependent microsomal formation of p-hydroxy-MP from MP, of p-hydroxy-Ph from p-hydroxy-MP, and the NADH-dependent microsomal formation of Ph from N-hydroxy-Ph.

来源:Hazardous Substances Data Bank (HSDB)

代谢

以下内容描述了在人类志愿者口服药物后几天内，美芬特明（I）及其主要代谢物芬特明（II）的尿液排泄情况。在54小时内，药物的总排泄比例为57%至83%。在服用美芬特明（I）后不久摄入乙酰唑胺，导致一天内美芬特明（I）和芬特明（II）的排泄量减少。而呋塞米的使用仅在给药后2-4小时内产生了尿液稀释效果。

The urinary excretion of mephentermine (I) and its major metabolite phentermine (II) in human volunteers over a period of several days after oral admin of the drug is described. The total proportion of the drug excreted during 54 hr was 57 to 83%. The ingestion of acetazolamide shortly after admin of I resulted in decr in excretion of both I and II during one day. The administration of furosemide only produced a urinary diluting effect during 2-4 hr after admin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在麻醉狗中，当在给予美芬特明后给予利血平时，利血平增强了升压反应。

IN ANESTHETIZED DOGS, RESERPINE POTENTIATED THE PRESSOR RESPONSE WHEN ADMIN AFTER MEPHENTERMINE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

苯丙胺和去甲肾上腺素在反复给猫和鼠注射时，对血压的反应迅速产生快速耐受性。对这些物质的快速耐受性是相互交叉的，并且与苯乙胺交叉，但不与酪胺交叉，因为作用部位不同。酪胺可能从与去甲肾上腺素、苯丙胺和苯乙胺不同的储存部位释放去甲肾上腺素，但这两个储存部位可能在功能上是相连的。

MEPHENTERMINE & DEXAMPHETAMINE SHOWED RAPID TACHYPHYLAXIS OF RESPONSES ON BLOOD PRESSURE WHEN REPEATED INJECTIONS ADMIN TO CATS & RATS. TACHYPHYLAXIS TO THESE SUBSTANCES WAS MUTUALLY CROSSED & WAS CROSSED TO PHENYLETHYLAMINE BUT NOT TO TYRAMINE BECAUSE OF SITE OF ACTION. TYRAMINE PROBABLY RELEASES NORADRENALINE FROM A DIFFERENT STORAGE SITE THAN DEXAMPHETAMINE, MEPHENTERMINE, & PHENYLETHYLAMINE BUT THE TWO STORES MAY BE FUNCTIONALLY CONNECTED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

非刺激剂量的1毫克/公斤的甲基苯非他明通过静脉给药给狗和兔子时产生了一种急性致偏头痛反应（AER）。预先用α-甲基-m-酪氨酸（100毫克/公斤）处理的兔子看起来正常，一致对外界刺激表现出脑电图激活，并对药物组合产生AER。5毫克/公斤的盐酸氯丙咪嗪预防了AER，而去甲基氯丙咪嗪没有阻止或改变其过程。1-5毫克/公斤的氢溴酸东莨菪碱只预防了AER的脑电图激活。预先用异烟肼（100毫克/公斤）处理延长了药物组合后的刺激，但没有改变甲基苯非他明单独的作用。用利血平预先处理兔子减少了或消除了甲基苯非他明引起的中枢神经系统刺激，但是阈剂量的甲基安非他明（1-5毫克/公斤）产生了中枢神经系统刺激。

MEPHENTERMINE IN NONSTIMULATING DOSES OF 1 MG/KG PRODUCED AN ACUTE ERGOTROPIC RESPONSE (AER) WHEN ADMIN IV WITH 1 MG/KG RESERPINE TO DOGS & RABBITS. RABBITS PRETREATED WITH ALPHA-METHYL-M-TYROSINE (100 MG/KG) APPEARED NORMAL, CONSISTENTLY MANIFESTED ELECTROENCEPHALOGRAPHIC ACTIVATION TO EXTEROCEPTIVE STIMULI, & DISPLAYED AER IN RESPONSE TO DRUG COMBINATION. 5 MG/KG OF IMIPRAMINE-HCL PREVENTED THE AER, WHILE DEMETHYLIMIPRAMIME DID NOT BLOCK OR ALTER ITS COURSE. 1-5 MG/KG OF SCOPOLAMINE HYDROGEN BROMIDE PREVENTED ONLY THE ELECTROENCEPHALIC ACTIVATION OF THE AER. PRETREATMENT WITH IPRONIAZID (100 MG/KG) PROLONGED THE STIMULATION FOLLOWING THE DRUG COMBINATION BUT DID NOT CHANGE THE ACTIONS OF MEPHENTERMINE ALONE. PRETREATMENT OF RABBITS WITH RESERPINE REDUCED OR ABOLISHED THE CNS STIMULATION CAUSED BY MEPHENTERMINE BUT THRESHOLD DOSES OF METHAMPHETAMINE (1-5 MG/KG) PRODUCED CNS STIMULATION.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

利血平（1毫克/千克）与美芬他明（1毫克/千克）联合使用，但不是利血平或美芬他明单独使用，在麻醉兔中产生了大约28分钟的电生理激活模式，并消除了中脑网状结构中的单次电击反应。氯丙嗪（5毫克/千克）阻断了这些药物的联合效果。利血平显然促进了美芬他明的间接作用，而大脑生物原胺的存在是实现这种刺激的必要条件。

RESERPINE (1 MG/KG) IN COMBINATION WITH MEPHENTERMINE (1 MG/KG) BUT NOT RESERPINE OR MEPHENTERMINE ALONE, PRODUCED ELECTROENCEPHALOGRAPH ACTIVATION PATTERN & ABOLISHED SINGLE SHOCK RESPONSES WITHIN MIDBRAIN RETICULAR FORMATION FOR ABOUT 28 MIN IN CURARIZED RABBITS. CHLORPROMAZINE (5 MG/KG) BLOCKED THE COMBINED EFFECT OF THE DRUGS. RESERPINE APPARENTLY FACILITATES INDIRECT ACTIONS OF MEPHENTERMINE, & THE PRESENCE OF BRAIN BIOGENIC AMINES ARE A REQUISITE TO THIS STIMULATION.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

过量治疗的推荐方法包括：对于过度的升压作用：应降低给药速率或暂时停止给药，直到血压下降。由于这些药物的持续时间短，通常不需要采取额外措施。然而，如果降低给药速率或停止治疗未能降低血压，可以给予短效α-肾上腺素能阻滞剂。/拟交感神经药 - 心血管用途/

Recommended treatment for overdose includes: For excessive hypertensive effect: The rate of administration should be reduced or the mediation temporarily discontinued until blood pressure is decreased. Additional measures are usually not necessary because the duration of action of these agents is short. However, if reduction in the rate of administration or discontinuation of therapy fails to lower the blood pressure, a short-acting alpha-adrenergic blocking agent may be administered. /Sympathomimetic agents - cardiovascular use/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...美芬特明.../在/消化道中吸收良好。 .../它/可能/在/鼻黏膜/吸收/程度/更高/或/更低。

...MEPHENTERMINE.../IS/ WELL ABSORBED FROM DIGESTIVE TRACT. .../IT/ MAY BE ABSORBED TO A GREATER OR LESSER EXTENT FROM NASAL MUCOSA.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

药物的大部分在24小时内通过尿液排出。美芬他明在肾小管中被重吸收。在酸性尿液中，药物及其代谢物的排泄速度更快。

THE MAJORITY OF THE DRUG IS EXCRETED IN THE URINE WITHIN 24 HR. MEPHENTERMINE IS REABSORBED IN THE RENAL TUBULES. EXCRETION OF THE DRUG & ITS METABOLITES IS MORE RAPID IN ACIDIC URINE.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  美芬丁胺 在 potassium carbonate 作用下， 以 甲苯 、 正丁醇 为溶剂， 生成 奥昔卡因
  参考文献：
  名称：

  A New Class of Local Anesthetics: Hydroxyalkyliminobisacetamides¹

  摘要：

  DOI：

  10.1021/jo01351a057
• 作为产物：
  描述：

  β-Hydroxymephentermin 在 氯化亚砜 作用下， 生成 美芬丁胺
  参考文献：
  名称：

  US2597445

  摘要：

  公开号：

文献信息

• [EN] SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1<br/>[FR] AGONISTES À PETITES MOLÉCULES DE RÉCEPTEUR DE NEUROTENSINE 1
  申请人：SANFORD BURNHAM MED RES INST

  公开号：WO2014100501A1

  公开（公告）日：2014-06-26

  Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

  提供的是小分子神经降压素受体激动剂，包含这些化合物的组合物，以及使用这些化合物和包含这些化合物的组合物的方法。
• [EN] BIOREVERSABLE PROMOIETIES FOR NITROGEN-CONTAINING AND HYDROXYL-CONTAINING DRUGS<br/>[FR] PRO-FRAGMENTS BIORÉVERSIBLES POUR MÉDICAMENTS CONTENANT DE L'AZOTE ET DE L'HYDROXYLE
  申请人：BAIKANG SUZHOU CO LTD

  公开号：WO2015081891A1

  公开（公告）日：2015-06-11

  Disclosed are promoieties of the following formula which can be used to form prodrugs of nitrogen-containing or hydroxyl-containing drug or a pharmaceutically active agent: (I) and pharmaceutical compositions comprising the prodrugs.

  披露了以下公式的促销性质，它们可用于形成含有氮或羟基的药物或药物活性剂的的前药：(I)以及包含这些前药的药物组合物。
• GLUTATHIONE-CHOLESTEROL DERIVATIVES AS BRAIN TARGETING AGENTS
  申请人：South Dakota Board of Regents

  公开号：US20200048305A1

  公开（公告）日：2020-02-13

  The present invention describes compositions containing cholesterol-linker-glutathione conjugates for targeting the brain by overcoming barrier entry to the CNS through the blood brain barrier (BBB), including micelle and liposome forms of such compositions. In addition, methods for treating subjects by administering such compositions are also disclosed.

  本发明描述了含有胆固醇-连接剂-谷胱甘肽共轭物的组合物，通过克服血脑屏障（BBB）进入中枢神经系统的屏障入口，包括这些组合物的胶束和脂质体形式。此外，还公开了通过给予这些组合物治疗受试者的方法。
• Base-stabilized polyorthoester formulations
  申请人：Shah T. Devang

  公开号：US20070264338A1

  公开（公告）日：2007-11-15

  A stabilized semi-solid delivery vehicle contains a polyorthoester and an excipient, and a pharmaceutical composition contains an active agent, optionally a stabilizing agent, and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.

  一种稳定的半固态给药载体包含聚正交酯和辅料，以及一种药物组合物包含活性药剂，可选地包含稳定剂和给药载体。该药物组合物可以是局部、可注射或可注射的配方；适用于活性药剂的局部给药。还公开了治疗方法。
• Sulfur(VI) fluoride compounds and methods for the preparation thereof
  申请人：The Scripps Research Institute

  公开号：US10117840B2

  公开（公告）日：2018-11-06

  This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

  该应用描述了由式(I)表示的化合物：(I)其中：Y是一个生物活性有机核心基团，包括芳基、杂芳基、非芳香烃基和非芳香杂环基中的一个或多个，其中Z与之以共价键结合；n为1、2、3、4或5；m为1或2；Z为O、NR或N；X1为共价键或—CH2CH2—，X2为O或NR；R包括H或从芳基、杂芳基、非芳香烃基和非芳香杂环基中选择的取代或未取代基团。还描述了制备这些化合物的方法、使用这些化合物的方法以及包含这些化合物的药物组合物。

表征谱图