甲基苯巴比妥 | 115-38-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 甲基苯巴比妥
• 中文别名: 甲苯比妥
• 英文名称: mephobarbital
• 英文别名: methylphenobarbital；5-ethyl-N-methyl-5-phenyl-barbituric acid；1-methyl-5-ethyl-5-phenylbarbituric acid；N-methylphenobarbital；methylphenobarbitone；5-ethyl-1-methyl-5-phenyl-1,3-diazinane-2,4,6-trione
• CAS: 115-38-8
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: ALARQZQTBTVLJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

肝脏，主要由肝脏微粒体酶系统代谢。大约75%的单次口服剂量甲戊巴比妥在24小时内代谢为苯巴比妥。

Hepatic, primarily by the hepatic microsomal enzyme system. About 75% of a single oral dose of mephobarbital is metabolized to phenobarbital in 24 hours.

来源:DrugBank

代谢

甲丙巴比妥的主要代谢途径是通过肝脏的N-脱甲基作用形成苯巴比妥。大约75%的单一口服剂量的甲丙巴比妥在24小时内转化为苯巴比妥。长期使用甲丙巴比妥会导致血浆中苯巴比妥（而不是甲丙巴比妥）的积累。目前尚未明确确定甲丙巴比妥是否有助于抗惊厥效果，或者是否只有代谢物苯巴比妥在甲丙巴比妥治疗期间是唯一的有效成分。苯巴比妥可能会以原形、p-羟基苯巴比妥代谢物、或者作为葡萄糖醛酸或硫酸盐结合物在尿液中排出。尿液碱化或增加尿流量可以显著提高未改变的苯巴比妥的排泄速率。

The principal route of mephobarbital metabolism is N-demethylation by the liver to form phenobarbital. About 75% of a single oral dose of mephobarbital is converted to phenobarbital in 24 hours. Chronic administration of mephobarbital leads to accumulation of phenobarbital (not mephobarbital) in plasma. It has not been definitely determined whether mephobarbital contributes to the anticonvulsant effect or whether the metabolite, phenobarbital, is the only active agent during mephobarbital therapy. Phenobarbital may be excreted in the urine unchanged, as the p-hydroxyphenobarbital metabolite, or as glucuronide or sulfate conjugates. Alkalinization of the urine and/or increasing the urine flow substantially increases the rate of excretion of unchanged phenobarbital.

来源:Hazardous Substances Data Bank (HSDB)

代谢

巴比妥类药物的代谢速度较慢，主要由肝脏微粒体酶系统进行。苯巴比妥和其他巴比妥类药物可能会诱导肝脏微粒体酶，从而可能加速同时给予的、通过这些酶代谢的其他药物的代谢。目前没有确凿的证据表明巴比妥类药物会加速自身的代谢。/巴比妥类药物总述/

Barbiturates are slowly metabolized, chiefly by hepatic microsomal enzymes. Phenobarbital and probably other barbiturates induce hepatic microsomal enzymes and thus may accelerate metabolism of other concomitantly administered drugs metabolized by these enzymes. There is no conclusive evidence that barbiturates accelerate their own metabolism. /Barbiturates General Statement/

来源:Hazardous Substances Data Bank (HSDB)

代谢

尚未确定甲丙巴比妥（mephobarbital）是否像苯巴比妥（phenobarbital）一样是参与其他药物代谢酶的强诱导剂，但由于甲丙巴比妥在化学和药理学上与苯巴比妥相似，并且可以代谢为苯巴比妥，因此这种可能性很大。

It has not been established whether mephobarbital, like phenobarbital, is a potent inducer of the enzymes involved in the metabolism of other drugs, but because the drug is chemically and pharmacologically similar to phenobarbital in addition to being metabolized to phenobarbital, this possibility is likely.

来源:Hazardous Substances Data Bank (HSDB)

代谢

甲基苯巴比妥（MPB）的代谢和药代动力学的立体选择性在六名健康成年男性志愿者中进行了研究，这些志愿者单次口服了消旋药物。所有志愿者在表型上都是药物的广泛代谢者。通过一种对映选择性高效液相色谱法分析了MPB的R-和S-对映体在血浆中的含量，以及通过类似程序分析了尿液中4-羟基-MPB代谢物的对映体。 (R)-MPB被广泛羟基化，平均有49.56%的该对映体以(R)-4-羟基-MPB的形式在尿液中回收。只有7.16%的(S)-MPB转化为了相应的羟基代谢物。 (R)-MPB的广泛羟基化导致这种对映体迅速消除，终末血浆半衰期为7.52 +/- 1.70（标准差）小时。 (S)-MPB的消除非常缓慢[t1/2, 69.78 +/- 14.77（标准差）小时]，其唯一认可的代谢物是(S)-4-羟基-MPB和苯巴比妥（PB）。 (R)-MPB的口服清除率（0.470 +/- 0.184（标准差）升/小时/千克）远高于(S)-MPB的清除率[0.017 +/- 0.001（标准差）升/小时/千克]。 MPB对映体在代谢命运和药代动力学上的极端差异非常有趣。大部分循环中的PB似乎来源于(S)-MPB。

The stereoselectivity of the metabolism and pharmacokinetics of methylphenobarbital (MPB) was studied in six healthy adult male volunteers given single oral doses of the racemic drug. All of the volunteers were phenotypically extensive metabolizers of the drug. The R- and S-enantiomers of MPB were analyzed in plasma by an enantioselective HPLC method, and the enantiomers of the 4-hydroxy-MPB metabolite in urine by a similar procedure. The (R)-MPB was extensively hydroxylated, with an average of 49.56% of that enantiomer being recovered in urine as (R)-4-hydroxy-MPB. Only 7.16% of the (S)-MPB was converted to the corresponding hydroxy metabolite. The extensive hydroxylation of (R)-MPB resulted in rapid elimination of this enantiomer, with a terminal plasma half-life of 7.52 +/- 1.70 (SD) hr. The (S)-MPB, the only recognized metabolites of which were (S)-4-hydroxy-MPB and phenobarbital (PB), was eliminated very slowly [t1/2, 69.78 +/- 14.77 (SD) hr]. The oral clearance of (R)-MPB (0.470 +/- 0.184 (SD) liters/hr/kg) was much higher than that of (S)-MPB [0.017 +/- 0.001 (SD) liters/hr/kg]. The extreme differences in metabolic fate and pharmacokinetics of the enantiomers of MPB are interesting. Most of the circulating PB seemed to be derived from (S)-MPB. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

苯巴比妥可能通过诱导代谢抗生素的肝微粒体酶，从而缩短多西环素的半衰期。如果可能的话，应避免同时使用多西环素和"巴比妥类药物"。如果需要联合治疗，可以在12小时给药一次，或者密切监测多西环素的浓度。/巴比妥类药物一般声明/

Phenobarbital may decrease the half-life of doxycycline by inducing hepatic microsomal enzymes that metabolize the antibiotic. Concomitant administration of doxycycline and "barbiturates" should be avoided if possible. If concomitant therapy is necessary, doxycycline may be administered at 12-hour intervals and/or doxycycline concentrations should be closely monitored. /Barbiturates General Statement/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

口服避孕药的同时使用苯巴比妥（或其他巴比妥类药物）可能会降低口服避孕药的效果。有报道称，在使用口服避孕药的同时接受抗惊厥药（如苯巴比妥）的女性仍然怀孕。苯巴比妥可能会增强口服避孕药中的雌激素和孕激素成分的代谢，这可能是通过诱导肝微粒体酶实现的。由于在使用口服避孕药和苯巴比妥（或美沙比妥）的同时存在避孕失败的风险，建议接受苯巴比妥治疗的患者考虑使用其他避孕方法。/巴比妥类药物一般声明/

Pretreatment with or concurrent administration of phenobarbital in patients receiving oral contraceptives may decrease the effectiveness of oral contraceptives. There have been reports of women receiving anticonvulsants (eg, phenobarbital) who became pregnant while receiving oral contraceptives. Phenobarbital may enhance the metabolism of both the estrogenic and progestinic components of oral contraceptives, presumably by induction of hepatic microsomal enzymes. Because of the risk of contraceptive failure during concomitant use of oral contraceptives and phenobarbital (or mephobarbital), it has been suggested that alternate methods of contraception be considered in patients receiving phenobarbital. /Barbiturates General Statement/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

巴比妥类药物可能会增强三环类抗抑郁药（如阿米替林、丙咪嗪）引起的毒性剂量不良反应（例如呼吸抑制）。在治疗剂量的三环类抗抑郁药中，巴比妥类药物似乎促进代谢并降低抗抑郁药的血药浓度；然而，这种效果的临床重要性尚未确立。/巴比妥类药物一般声明/

"Barbiturates" may potentiate adverse effects (e.g., respiratory depression) induced by toxic doses of tricyclic antidepressants (e.g., amitriptyline, imipramine). With therapeutic doses of tricyclic antidepressants, "barbiturates" appear to stimulate metabolism and decrease blood concentrations of the antidepressants; however, the clinical importance of this effect has not been established. /Barbiturates General Statement/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

巴比妥类药物（尤其是苯巴比妥）可能会减少二甘醇从胃肠道（GI）的吸收。此外，苯巴比妥以及其他可能的巴比妥类药物可能会诱导肝微粒体酶，导致香豆素抗凝剂代谢增加，抗凝反应降低。如果停用巴比妥类药物而未调整抗凝剂的剂量，那么同时使用巴比妥类药物和香豆素抗凝剂的患者的出血风险会增加。在接受口服抗凝剂的患者中，不应启动或停止巴比妥类药物治疗，除非仔细考虑到可能需要调整抗凝剂剂量的需求。

"Barbiturates", especially phenobarbital, may decrease absorption of dicumarol from the GI tract. In addition, phenobarbital and possibly other "barbiturates" may induce hepatic microsomal enzymes resulting in increased metabolism of coumarin anticoagulants and decreased anticoagulant response. Patients maintained on both "barbiturates" and a coumarin anticoagulant have a risk of hemorrhage if the barbiturate is discontinued and the dosage of the anticoagulant is not adjusted. Barbiturate therapy should not be initiated or discontinued in patients receiving oral anticoagulants without careful attention to the possible need for adjusting anticoagulant dosage.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

一位38岁的女性根据病史摄入了13克甲基苯巴比妥、酒精和6克对乙酰氨基酚，在4天内逐渐陷入昏迷。急性肝损伤似乎影响了甲基苯巴比妥的氧化N-去甲基化，从而产生其代谢产物苯巴比妥。摄入后的第八天，由于长期昏迷，她接受了Amberlite XAD-4树脂血液灌流治疗。血液灌流清除了0.83克甲基苯巴比妥和2.10克苯巴比妥，这导致了短暂的临床改善。当支持性患者管理未能使甲基苯巴比妥中毒患者产生满意的临床过程时，血液灌流可能成为治疗的有用辅助手段。

A 38-yr-old woman who by history ingested 13 g methylphenobarbital, alcohol, and 6 g acetaminophen became comatose slowly over 4 days. Acute hepatic injury appeared to impair the oxidative N-demethylation of methylphenobarbital to its product, phenobarbital. On the eighth day after ingestion she was treated because of protracted coma with Amberlite XAD-4 resin hemoperfusion. Hemoperfusion, which removed 0.83 g methylphenobarbital and 2.10 g phenobarbital, led to transient clinical improvement. When supportive patient management fails to produce a satisfactory clinical course in a methylphenobarbital-intoxicated patient, hemoperfusion could be a useful adjunct to therapy.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

大约50%的口服剂量从中枢神经系统被吸收。

Approximately 50% of an oral dose of mephobarbital is absorbed from the gastrointestinal tract.

来源:DrugBank

吸收、分配和排泄

大约50%的口服剂量从中枢神经系统被吸收。用于治疗作用的血浆浓度尚不清楚。

Approximately 50% of an oral dose of mephobarbital is absorbed from the GI tract. Plasma concentrations required for therapeutic effects are unknown.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

巴比妥类药物在口服、直肠或肌肉注射后以不同程度被吸收。钠盐通过所有给药途径的吸收速度都比相应的酸快。当钠盐作为稀释溶液摄入或空腹服用时，口服吸收速率增加。酒精也提高了吸收速率，可能是通过增加通过胃粘膜的血流量。/巴比妥类药物概述/

Barbiturates are absorbed in varying degrees following oral, rectal, or im administration. The sodium salts are more rapidly absorbed by all routes of administration than are the acids. The rate of oral absorption is increased when the sodium salt is ingested as a dilute solution or taken on an empty stomach. Alcohol also enhances the rate of absorption, possibly by increasing blood flow through the gastric mucosa. /Barbiturates General Statement/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服或直肠给药后，药物的作用开始时间从... 20-60分钟不等，对于甲基巴比妥、甲戊巴比妥和苯巴比妥。肌内注射给药会使作用开始时间稍微快一些。静脉注射阿莫巴比妥、戊巴比妥、苯巴比妥或司可巴比妥的钠盐后，作用开始时间从几乎立即对甲己巴比妥、戊巴比妥和硫喷妥到5分钟对苯巴比妥不等。硫喷妥或戊巴比妥的最大效果在大约1分钟内达到，而苯巴比妥可能需要多达30分钟。/巴比妥类药物一般声明/

Following oral or rectal administration, the onset of action varies from ... 20-60 minutes for metharbital, mephobarbital, and phenobarbital. IM administration results in a slightly faster onset of action. Following iv administration of the sodium salts of amobarbital, pentobarbital, phenobarbital, or secobarbital, the onset of action ranges from almost immediately for methohexital, pentobarbital, and thiopental to 5 minutes for phenobarbital. Maximum effects of thiopental or pentobarbital are achieved within about 1 minute while as much as 30 minutes may be required with administration of phenobarbital. /Barbiturates General Statement/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

所有巴比妥类药物的镇静效果持续时间通常为静脉注射后3-6小时，其他给药途径则为6-8小时。口服作为催眠药使用的巴比妥类药物之间催眠作用的持续时间似乎没有太大差异。因此，现在大多数权威机构认为应该根据巴比妥类药物预定的药理作用进行分类（即，镇静催眠巴比妥类药物和麻醉巴比妥类药物[戊巴比妥，硫喷妥钠（在美国已不再商业供应），硫戊巴比妥]），而不是按照长效（美沙比妥，甲己比妥，苯巴比妥），中效（阿莫比妥和丁比妥），短效（阿普比妥，戊巴比妥和司可巴比妥），超短效（戊巴比妥，硫喷妥钠）来分类。/巴比妥类药物一般声明/

The duration of sedative effects of all the barbiturates is usually 3-6 hours following iv administration and 6-8 hours when the drugs are administered by other routes. There appears to be very little difference in duration of hypnotic action among barbiturates used orally as hypnotics. Therefore, most authorities now believe that barbiturates should be classified according to their intended pharmacologic action (ie, sedative-hypnotic barbiturates and anesthetic barbiturates [methohexital, thiamylal (no longer commercially available in the US), thiopental]), rather than as long-acting (mephobarbital, metharbital, and phenobarbital), intermediate-acting (amobarbital and butabarbital), short-acting (aprobarbital, pentobarbital, and secobarbital), and ultrashort-acting (methohexital, thiopental). /Barbiturates General Statement/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法

催眠镇静药。

用途简介

暂无相关信息。

用途

催眠镇静药。

反应信息

• 作为反应物：
  描述：

  甲基苯巴比妥 生成 美芬妥英
  参考文献：
  名称：

  Barton; Zurowska; Bojarski, Pharmazie, 1983, vol. 38, # 4, p. 268 - 268

  摘要：

  DOI：
• 作为产物：
  描述：

  苯巴比妥 在 硫酸二甲酯 作用下， 生成 甲基苯巴比妥
  参考文献：
  名称：

  US1923239

  摘要：

  公开号：

文献信息

• [EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
  申请人：GALLEON PHARMACEUTICALS INC

  公开号：WO2009151744A1

  公开（公告）日：2009-12-17

  The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.

  本发明涉及基于巯基和S-亚硝基巯基的SNO化合物及其衍生物，以及它们在治疗正常呼吸控制缺失方面的用途，包括治疗与睡眠、肥胖、某些药物和其他医疗状况相关的呼吸暂停和低通气。
• [EN] COMPOUNDS AND THEIR USE AS BACE INHIBITORS<br/>[FR] COMPOSÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BACE
  申请人：ASTRAZENECA AB

  公开号：WO2016055858A1

  公开（公告）日：2016-04-14

  The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.

  本申请涉及式(I)、(Ia)或(Ib)的化合物及其药物组合物/制剂。本申请进一步涉及治疗或预防与Αβ相关的病理学，如唐氏综合症，β-淀粉样蛋白血管病，如但不限于脑淀粉样蛋白血管病或遗传性脑出血，与认知损害相关的疾病，如但不限于MCI（“轻度认知损害”），阿尔茨海默病，记忆丧失，与阿尔茨海默病相关的注意力缺陷症状，与疾病如阿尔茨海默病或痴呆症相关的神经退行性疾病，包括混合性血管性和退行性起源的痴呆，早老性痴呆，老年性痴呆和与帕金森病相关的痴呆的方法。
• [EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089721A1

  公开（公告）日：2016-06-09

  The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及甲基噁唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述化合物在潜在治疗或预防涉及促进睡眠的神经和精神疾病和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及促进睡眠的疾病中的用途。
• HETEROBICYCLIC COMPOUNDS
  申请人：Amgen Inc.

  公开号：US20130225552A1

  公开（公告）日：2013-08-29

  Heterobicyclic compounds of Formula (I): or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.

  Formula (I)的杂环化合物： 或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。

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