(1S,2S)-2-甲氨基-1-苯基丙-1-醇 | 90-82-4

• 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: (1S,2S)-2-甲氨基-1-苯基丙-1-醇
• 中文别名: 右旋伪麻黄碱；伪麻黄碱
• 英文名称: pseudoephedrine
• 英文别名: (1S,2S)-(+)-pseudoephedrine；(S,S)-pseudoephedrine；D-pseudoephedrine；(+) ephedrine；(1S,2S)-2-(methylamino)-1-phenylpropan-1-ol；(+)-pseudoephedrin；(1S,2S)-ephedrine；decorin；Pse
• CAS: 90-82-4
• 化学式: C₁₀H₁₅NO
• 分子量: 165.235
• InChiKey: KWGRBVOPPLSCSI-WCBMZHEXSA-N

物化性质

• 稳定性/保质期：

  在常温常压下稳定。

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

伪麻黄碱有不到1%被N-去甲基化为无活性代谢物。大部分伪麻黄碱以未代谢的形式通过尿液排出。

Pseudoephedrine is <1% N-demethylated to an inactive metabolite. The majority of pseudoephedrine is eliminated unmetabolized in the urine.

来源:DrugBank

代谢

伪麻黄碱在肝脏通过N-去甲基化部分代谢（小于1%）成一个无活性的代谢物。药物及其代谢物通过尿液排出；55-96%的剂量以原形排出。

Pseudoephedrine is incompletely metabolized (less than 1%) in the liver by N-demethylation to an inactive metabolite. The drug and its metabolite are excreted in urine; 55-96% of a dose is excreted unchanged.

来源:Hazardous Substances Data Bank (HSDB)

代谢

D-伪麻黄碱产生D-去甲伪麻黄碱 & L-伪麻黄碱产生L-去甲伪麻黄碱 在兔中：DANN, RE等，EUR J PHARMAC，16，233（1971）。/来自表格/

D-PSEUDOEPHEDRINE YIELDS D-NORPSEUDOEPHEDRINE & L-PSEUDOEPHEDRINE YIELDS L-NORPSEUDOEPHEDRINE IN RABBIT: DANN, RE ET AL, EUR J PHARMAC, 16, 233 (1971). /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

麻黄碱（EPH）、伪麻黄碱（PEPH）、苯丙醇胺（PPA）、甲基麻黄碱（MEPH）和卡西酮都是拟交感神经胺类药物。对麻黄碱相关药物进行了排泄研究，以更好地理解麻黄碱在尿液中的代谢产量。在志愿者（每种药物各3人）服用单一临床剂量的这些药物后，收集尿液样本，进行叔丁基甲基醚（TBME）提取和三氟乙酸（TFAA）衍生化处理，然后进行气相色谱-质谱（GC-MS）分析。大部分麻黄碱类药物以原形在尿液中排出，包括EPH（40.9%）、PEPH（72.2%）和PPA（59.3%）。然而，只有相对少量的MEPH（15.5%）以原形排出。此外，还发现PPA（1.6%）和卡西酮（0.7%）分别是EPH和PEPH的代谢物。尿液中EPH、PEPH和PPA在给药后2-6小时达到峰值，在约24-48小时后从尿液中消失。

Ephedrine (EPH), pseudoephedrine (PEPH), phenylpropanolamine (PPA), methylephedrine (MEPH) and cathine are sympathomimetic amines. ... Excretion studies of the ephedrine-related drugs have been performed to better understand the metabolic yields of ephedrines in urine. After consuming a single clinical dose of each of these drugs, urine samples from volunteers (n=3 for each drug) were subjected to tert-butyl-methyl-ether (TBME) extraction and trifluoroacetic acid (TFAA) derivatization before gas chromatography-mass spectrometry (GC-MS) analysis. Most ephedrines were excreted unchanged in urine, including EPH (40.9%), PEPH (72.2%), and PPA (59.3%). However, only a relatively small amount of MEPH (15.5%) was excreted unchanged in urine. In addition, a trace amount of PPA (1.6%) and cathine (0.7%) was found to be the metabolites of EPH and PEPH, respectively. Urinary EPH, PEPH, and PPA reached peaks at 2-6 hr and disappeared in urine at approximately 24-48 hr post-administration. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏的。 半衰期：9-16小时

Hepatic. Half Life: 9-16 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

伪麻黄碱对α-和β-肾上腺素能受体都有直接作用，尽管对β-肾上腺素能受体的作用程度较小。伪麻黄碱通过直接作用于呼吸道粘膜的α-肾上腺素能受体，产生血管收缩。伪麻黄碱通过刺激β2-肾上腺素能受体来放松支气管平滑肌。与麻黄碱类似，伪麻黄碱从其储存位点释放去甲肾上腺素，这是一种间接效应。这是其主要和直接的作用机制。被替换的去甲肾上腺素被释放到神经元突触中，自由地激活突触后的肾上腺素能受体。

Pseudoephedrine acts directly on both alpha- and, to a lesser degree, beta-adrenergic receptors. Through direct action on alpha-adrenergic receptors in the mucosa of the respiratory tract, pseudoephedrine produces vasoconstriction. Pseudoephedrine relaxes bronchial smooth muscle by stimulating beta2-adrenergic receptors. Like ephedrine, pseudoephedrine releasing norepinephrine from its storage sites, an indirect effect. This is its main and direct mechanism of action. The displaced noradrenaline is released into the neuronal synapse where it is free to activate the postsynaptic adrenergic receptors.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

化合物：伪麻黄碱

Compound:pseudoephedrine

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注释：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：没有匹配项

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

一个 240 毫克的伪麻黄碱口服剂量，在进食状态下达到 246.3±10.5 纳克/毫升的Cmax，空腹状态下达到 272.5±13.4 纳克/毫升的Cmax，进食状态下的Tmax为 6.60±1.38 小时，空腹状态下的Tmax为 11.87±0.72 小时，进食状态下的AUC为 6862.0±334.1 纳克*小时/毫升，空腹状态下的AUC为 7535.1±333.0 纳克*小时/毫升。

A 240mg oral dose of pseudoephedrine reaches a Cmax of 246.3±10.5ng/mL fed and 272.5±13.4ng/mL fasted, with a Tmax of 6.60±1.38h fed and 11.87±0.72h fasted, with an AUC of 6862.0±334.1ng\*h/mL fed and 7535.1±333.0ng\*h/mL fasted.

来源:DrugBank

吸收、分配和排泄

• 消除途径

55-75%的口服剂量以未改变的伪麻黄碱形式在尿液中检测到。

55-75% of an oral dose is detected in the urine as unchanged pseudoephedrine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

伪麻黄碱的表观分布容积为2.6-3.3升/千克。

The apparent volume of distribution of pseudoephedrin is 2.6-3.3L/kg.

来源:DrugBank

吸收、分配和排泄

• 清除

伪麻黄碱60毫克口服剂量的清除率为5.9±1.7毫升/分钟/千克。

A 60mg oral dose of pseudoephedrine has a clearance of 5.9±1.7mL/min/kg.

来源:DrugBank

吸收、分配和排泄

消除：肾脏。大约55至75%的剂量以原形排泄。在酸性尿液中，排泄速率加快。

Elimination: Renal. About 55 to 75% of a dose is excreted unchange. The rate of excretion is accelerated in acidic urine.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

用途

主要用于生化研究