Lorpiprazole | 108785-69-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Lorpiprazole
• 英文别名: (1S,8R)-5-[2-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]ethyl]-3,4,6-triazatricyclo[6.3.0.02,6]undeca-2,4-diene
• CAS: 108785-69-9；1640293-37-3
• 化学式: C₂₁H₂₆F₃N₅
• 分子量: 405.5
• InChiKey: BNRMWKUVWLKDQJ-YJBOKZPZSA-N

物化性质

• 熔点：
  138 ºC
• 水溶性：
  -3.63

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  37.2
• 氢给体数：
  0
• 氢受体数：
  7

ADMET

代谢

血清素拮抗剂和再摄取抑制剂，如氯吡格雷，在肝脏中被CYP450同工酶代谢，主要是CYP2D6和CYP3A4。[A31635]

Serotonin antagonists and reuptake inhibitors like lorpiprazole are metabolized in the liver by the CYP450 isoenzymes, mainly CYP2D6 and CYP3A4.[A31635]

来源:DrugBank

毒理性

• 毒性总结

5-HT拮抗剂和再摄取抑制剂的副作用较小，罕见报告有心脏毒性。据报道，它们会导致交感神经和副交感神经系统之间的失衡。还有关于这些药物可能具有肝毒性的报道。[T86]

The serotonin antagonists and reuptake inhibitors' side effects are minor with rare reports of cardiotoxicity. They have been reported to cause an unbalance between the sympathetic and parasympathetic system. There are also reports regarding a potential hepatotoxic effect of this drugs.[T86]

来源:DrugBank

毒理性

• 蛋白质结合

血清蛋白结合率预计会非常高，甚至高达89-99%。

The plasma protein binding of serotonin antagonists and reuptake inhibitors like lorpiprazole is expected to be very high and correspond to even 89-99% of the administered dose.[T86]

来源:DrugBank

吸收、分配和排泄

• 吸收

口服给药后，5-羟色胺拮抗剂和再摄取抑制剂在胃肠道中被迅速吸收。这种吸收可能会因为饮食的类型而减慢。这类药物的最大血浆浓度大约在给药后1小时出现。[T86]

After oral administration, the serotonin antagonist and reuptake inhibitors are rapidly absorbed in the gastrointestinal tract. This absorption can be slow down depending on the type of diet. The maximum plasma concentration of this kind of drugs occurs approximately 1 hour after administration.[T86]

来源:DrugBank

吸收、分配和排泄

• 消除途径

预计属于血清素拮抗剂和再摄取抑制剂类别的药物（如洛匹普拉唑）的消除将具有双相特征，其中大部分代谢的药物应通过尿液排出。

The elimination of drugs that fit in the category of serotonin antagonists and reuptake inhibitors like lorpiprazole is expected to have a biphasic profile in which most of the metabolized drug should be disposed of by the urine.[T86]

来源:DrugBank

吸收、分配和排泄

• 分布容积

5-HT拮抗剂和再摄取抑制剂如氯吡格雷可迅速通过血脑屏障，在脑内达到比血浆中更高的浓度。[T86]

The serotonin antagonists and reuptake inhibitors as lorpiprazole are quickly distributed through the blood-brain-barrier getting concentrated in the brain to even higher levels than the ones found in plasma.[T86]

来源:DrugBank

文献信息

• [EN] NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2<br/>[FR] MODULATEURS ALLOSTÉRIQUES NÉGATIFS DU RÉCEPTEUR MÉTABOTROPIQUE DU GLUTAMATE DE TYPE 2
  申请人：UNIV VANDERBILT

  公开号：WO2016149324A1

  公开（公告）日：2016-09-22

  Described are negative allosteric modulators of metabotropic glutamate receptor 2 (mGlu2), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, anxiety, obsessive-compulsive disorder, cognitive disorders, Alzheimer's disease, or autism spectrum disorders in a subject.

  描述了代谢型谷氨酸受体2（mGlu2）的负变构调节剂，包括这些化合物的药物组合物，以及使用这些化合物和组合物治疗受试者的抑郁症、焦虑症、强迫症、认知障碍、阿尔茨海默病或自闭症谱系障碍的方法。
• NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 3
  申请人：Vanderbilt University

  公开号：US20150361081A1

  公开（公告）日：2015-12-17

  Described are negative allosteric modulators of metabotropic glutamate receptor 3 (mGlu 3 ), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, cognitive disorders, schizophrenia, Alzheimer's disease, or cancer in a subject.

  描述了负性变构调节剂对代谢型谷氨酸受体3（mGlu3）的作用，包括这些化合物的药物组合物，以及使用这些化合物和组合物治疗主体的抑郁症、认知障碍、精神分裂症、阿尔茨海默病或癌症的方法。
• [EN] SOLID ORAL DOSAGE FORMS OF 2R,6R-HYDROXYNORKETAMINE OR DERIVATIVES THEREOF<br/>[FR] FORMES POSOLOGIQUES SOLIDES ORALES DE 2R, 6R-HYDROXYNORKÉTAMINE OU LEURS DÉRIVÉS
  申请人：SMALL PHARMA LTD

  公开号：WO2017208031A1

  公开（公告）日：2017-12-07

  This invention relates to solid oral dosage forms of 2R,6R-hydroxynorketamine or prodrugs thereof having Formula Ib, including any pharmaceutically acceptable salt of the foregoing, for use in a therapeutic method for the treatment of a depressive disorder in a patient.

  这项发明涉及具有公式Ib的2R,6R-羟基诺可胺或其前药的固体口服剂型，包括上述任何药用可接受盐，用于治疗患者的抑郁症的治疗方法。
• NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2
  申请人：Vanderbilt University

  公开号：US20160214940A1

  公开（公告）日：2016-07-28

  Described are negative allosteric modulators of metabotropic glutamate receptor 2 (mGlu 2 ), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, anxiety, obsessive-compulsive disorder, cognitive disorders, Alzheimer's disease, or autism spectrum disorders in a subject.

  本发明涉及一种负向变构调节剂，用于代谢型谷氨酸受体2（mGlu2），包括该化合物的药物组合物以及使用该化合物和组合物治疗主体的抑郁症、焦虑症、强迫症、认知障碍、阿尔茨海默病或自闭症谱系障碍的方法。
• METHOD FOR PREDICTING A TREATMENT RESPONSE TO A V1B RECEPTOR ANTAGONIST IN A PATIENT WITH DEPRESSIVE SYMPTOMS AND/OR ANXIETY SYMPTOMS
  申请人：B.R.A.H.M.S GmbH

  公开号：EP3276010A1

  公开（公告）日：2018-01-31

  The invention relates to a method for predicting a treatment response to a V1B receptor antagonist in a patient with depressive symptoms and/or anxiety symptoms, wherein the copeptin concentration in a blood sample of said patient is determined and/or the AVP concentration in a sample of cerebrospinal fluid of said patient is determined and wherein an elevated copeptin and/or an elevated AVP concentration compared to copeptin and/or AVP concentrations in healthy individuals is indicative for a patient responding to a treatment with a V1B receptor antagonist.

  本发明涉及一种预测抑郁症状和/或焦虑症状患者对 V1B 受体拮抗剂治疗反应的方法，其中测定了所述患者血液样本中的 copeptin 浓度和/或所述患者脑脊液样本中的 AVP 浓度，与健康人的 copeptin 和/或 AVP 浓度相比，copeptin 和/或 AVP 浓度升高表明患者对 V1B 受体拮抗剂治疗有反应。