烯丙吗啡 | 62-67-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 中文名称: 烯丙吗啡
• 中文别名: 醋托啡
• 英文名称: Nalorphin
• 英文别名: N-allylnormorphine；Nalorphine；Acetorfin；N-demethyl-N-allylmorphine；(-)-N-allylnalorphine；(-)-nalorphine；(4R,4aR,7S,7aR,12bS)-3-prop-2-enyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol
• CAS: 62-67-9
• 化学式: C₁₉H₂₁NO₃
• 分子量: 311.381
• InChiKey: UIQMVEYFGZJHCZ-SSTWWWIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  52.9
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

吗啡-3-葡萄糖苷酸二水合物和吗啡-6-葡萄糖苷酸作为狗体内纳洛芬的尿液代谢物被分离出来，而在猫体内分离出了吗啡-3-乙醚硫酸盐和吗啡-3-葡萄糖苷酸二水合物。...

Nalorphine-3-glucuronide dihydrate and nalorphine-6-glucuronide were isolated as urinary metabolites of nalorphine in dogs, and nalorphine-3-ethereal sulfate and nalorphine-3-glucuronide dihydrate were isolated in cats. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

纳洛芬在小兔体内产生2-羟基纳洛芬和纳洛芬-3-β-D-葡萄糖苷酸；在大鼠体内产生吗啡。

Nalorphine yields 2-hydroxynalorphine & nalorphine-3-beta-d-glucuronide in rabbit; yields normorphine in rat. /from table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

纳洛芬经肠道外给药比口服给药更有效，这可能是由于它在肝脏中迅速被生物转化（主要是通过和葡萄糖醛酸结合）。/SRP：以前的用途/

... Nalrophine is much more effective after parenteral than oral admin, probably because of rapid biotransformation in liver (mainly through conjugation with glucuronic acid). /SRP: former use/

来源:Hazardous Substances Data Bank (HSDB)

代谢

纳洛芬-盐酸首次通过效应在大鼠体内进行了测量，纳洛芬的主要代谢途径是N-脱烯基化和葡萄糖苷酸化。/纳洛芬 HCl/

First-pass effect of nalorphine-hydrogen chloride was measured in rats, major metabolic pathway for nalorphine was n-deallylation and glucuronidation. /Nalorphine HCl/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

当吗啡和纳洛芬一起以不同剂量肌肉注射时，对呼吸的影响是复杂的：使用5毫克吗啡时，增加纳洛芬的剂量产生的呼吸抑制比使用10毫克吗啡时增加的抑制更严重。这两种药物之间的相互作用被视为“竞争性双重性”的一个例子。纳洛芬对吗啡引起的呼吸抑制的拮抗作用主要与每种药物内在作用的差异有关，而不仅仅是由于相互竞争对某些受体位点的亲和力。

When both morphine and nalorphine were given together, intramuscularly, in varying dosages, the resulting effects on the respiration were complex: with 5 mg of morphine, increasing the dose of nalorphine produced greater depression than increasing it with 10 mg morphine. The interaction of the two drugs was regarded as an example of "competitive dualism". The antagonism by nalorphine of the respiratory depression produced by morphine was primarily related to differences in the intrinsic action of each drug, and not simply due to mutually competitive affinities for certain receptor sites.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

呼吸抑制剂作用的纳洛芬型拮抗剂可能会增加由中枢神经系统抑制剂产生的现有呼吸抑制。

... Resp depressant actions of nalorphine-type antagonists may add to existing resp depression produced by CNS depressants.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

盐酸纳洛芬据报道增强了接受苯乙肼/和其他单胺氧化酶抑制剂/的患者因注射美喷痛-左洛啡烷组合而引起的抑郁... /盐酸纳洛芬/

Nalorphine HBR reportedly enhanced depression caused by combination injection of meperidine-levallorphan in pt receiving phenelzine /and other monoamine oxidase inhibitors/ ... /Nalorphine hydrobromide/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者身体前倾或将其置于左侧（如果可能，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预期癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

纳洛芬口服吸收差。当通过注射给药时，它容易通过血脑屏障和胎盘。它主要在肝脏代谢并在尿液中排出。大约2%到6%的剂量以原形在尿液中排出。

Nalorphine is poorly absorbed when given by mouth. When administered by injection, it readily passes into the brain and across the placenta. It is largely metabolised in the liver and excreted in the urine. About 2 to 6% of the dose is excreted unchanged in the urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...与纳洛芬相比，纳洛酮在大脑/血浆中的比例和血浆蛋白结合程度显著更高。在注射10毫克/千克皮下剂量后96小时内，作为剂量的百分比，尿液和粪便中排出的游离纳洛酮量分别为4.1和3.9（纳洛芬为4.7和8.3）；结合型药物为15.4和1.2（纳洛芬为13和0.9）；总放射性物质为43.3和20.9（纳洛芬为34.8和19.2），分别对应上述数据。...

... The brain/plasma ratios and degree of plasma-protein binding were significantly higher for naloxone as compared to nalorphine. The amounts of free naloxone excreted as a percentage of the dose in urine and feces 96 hours after injection of the 10 mg/kg sc dose were 4.1 and 3.9 (for nalorphine 4.7 and 8.3); conjugated drug 15.4 and 1.2 (for nalorphine 13 and 0.9); total radioactivity 43.3 and 20.9 (for nalorphine 34.8 and 19.2), respectively. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在这项研究中，研究了纳洛芬的消除，以表征有机阳离子在肾脏和肝脏排泄之间的关系。纳洛芬通过肾脏和肝脏有效排泄。然而，在成年大鼠中，它的肝脏排泄占主导地位。在20天大的幼年动物中，胆汁纳洛芬消除尚未成熟，排泄量显著较低。纳洛芬的肾脏排泄在两个年龄组的大鼠中非常相似。在胆管结扎后，成年大鼠的纳洛芬肾脏排泄显著增加，而在幼年大鼠中保持不变。值得注意的是，在双侧肾切除术后，两个年龄组的纳洛芬肝脏排泄甚至减少。在进一步的实验中，成年大鼠在重复给予三乙酰甲烷、三碘甲状腺原氨酸或地塞米松后，纳洛芬的肾脏排泄可以得到刺激；这些处理对纳洛芬的胆汁分泌没有影响。

In this study, the elimination of nalorphine was investigated to characterize the relation between renal and hepatic excretion of organic cations. Nalorphine is excreted effectively both via kidney and liver. However, its hepatic excretion dominates in adult rats. In young, 20-day-old animals biliary nalorphine elimination is immature and the excreted amounts are significantly lower. Renal excretion of nalorphine is quite similar in rats of both ages. After bile duct ligation renal excretion of nalorphine increases significantly in adult rats whereas it remains unchanged in young ones. Remarkably, after bilateral nephrectomy hepatic elimination of nalorphine is even diminished in both age groups. In further experiments renal excretion of nalorphine could be stimulated in adult rats after repeated administration of trometamol, triiodothyronine, or dexamethasone; these treatments had no consequences on biliary secretion of nalorphine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

纳洛芬静脉注射后，其在大脑中的浓度比等效剂量的吗啡高出3-4倍。大脑中的浓度迅速下降，4小时后仅能检测到微量。

Following parenteral admin of nalorphine, concn in brain are 3-4 times higher than after comparable doses of morphine. Brain concn fall rapidly and only trace amt are found after 4 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

纳洛芬-HCl的一阶效应，大约50%的管理放射性在48小时后通过呼出的空气（14）CO2和尿液（结合的和未改变的纳洛芬）排出，这表明吸收基本完成。/纳洛芬 HCl/

First-pass effect of nalorphine-HCl, about 50% of admin radioactivity was excreted in expired air (14)CO2 and urine (conjugated and unchanged nalorphine) by 48 hr after either iv or oral admin suggesting that absorption was essentially complete. /Nalorphine HCl/

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  烯丙吗啡 在 碳酸氢钠 、 silver carbonate 作用下， 以 苯 为溶剂， 生成 O1-(3-acetoxy-17-allyl-4,5α-epoxy-morphin-7-en-6α-yl)-O2,O3,O4-triacetyl-β-D-glucopyranuronic acid methyl ester
  参考文献：
  名称：

  药物代谢。LXXII。纳洛啡-3-和-6-葡萄糖醛酸苷的合成及兔纳洛啡尿代谢产物的鉴定。

  摘要：

  按照合成吗啡葡萄糖醛酸的方法合成了纳洛啡-3-和-6-葡萄糖醛酸。然后利用这些葡萄糖醛酸苷作为鉴定家兔体内纳洛啡尿液代谢物的参考标准，确定纳洛啡-3-葡萄糖醛酸苷为主要代谢物。在 24 小时尿液样本中，除了检测到少量未改变的纳洛啡外，未检测到其他代谢物。本研究和以往研究中采用的尿液葡萄糖醛酸苷分离程序被证实非常有效，尤其是对吗啡生物碱而言。

  DOI：

  10.1248/cpb.18.2548
• 作为产物：
  描述：

  4,5α-epoxy-3,6α-bis-vinyloxycarbonyloxy-morphin-7-ene; hydrobromide 在 盐酸 、 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 烯丙吗啡
  参考文献：
  名称：

  Value of the vinyloxycarbonyl unit in hydroxyl protection: application to the synthesis of nalorphine

  摘要：

  DOI：

  10.1016/s0040-4039(01)93105-3

文献信息

• Controlled-release compositions containing opioid agonist and antagonist
  申请人：——

  公开号：US20020010127A1

  公开（公告）日：2002-01-24

  Controlled-release dosage forms containing an opioid agonist; an opioid antagonist; and a controlled release material release during a dosing interval an analgesic or sub-analgesic amount of the opioid agonist along with an amount of said opioid antagonist effective to attenuate a side effect of said opioid agonist. The dosage form provides analgesia for at least about 8 hours when administered to human patients. In other embodiments, the dose of antagonist released during the dosing interval enhances the analgesic potency of the opioid agonist.

  含有阿片激动剂、阿片拮抗剂和受控释放材料的控释剂型，其在给药间隔期间释放阿片激动剂的镇痛或亚镇痛量以及足以减轻所述阿片激动剂的副作用的阿片拮抗剂的量。当给予人类患者时，该剂型提供至少约8小时的镇痛作用。在其他实施例中，给药间隔期释放的拮抗剂剂量增强了阿片激动剂的镇痛效力。
• Substituted 1,3-thiazole compounds, their production and use
  申请人：——

  公开号：US20040053973A1

  公开（公告）日：2004-03-18

  (1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.

  (1) 一种1,3-噻唑化合物，其5位被取代为含有一个取代基的4-吡啶基团，该取代基不包括芳香基，或者(2) 一种1,3-噻唑化合物，其5位被取代为一个吡啶基团，该吡啶基团的氮原子邻近位置有一个取代基，该取代基不包括芳香基，具有出色的p38 MAP激酶抑制活性。
• PROCESS FOR THE PRODUCTION OF OPIATES
  申请人：Francis A. Charles

  公开号：US20050261500A1

  公开（公告）日：2005-11-24

  A morphine component, e.g., a concentrate of poppy straw, is converted into codeine in high yield and high purity and in a highly controlled manner. The conversion process involves the following steps: (a) providing a solution or suspension of a morphine component in an inert solvent or a mixture of solvents; (b) methylating the resultant solution or suspension with a methylating agent in the presence of an alkaline ingredient; and (c) recovering the resultant codeine as the free base or as a salt.

  一种吗啡成分，例如罂粟秸秆浓缩物，以高产率、高纯度和高度受控的方式转化为可待因。转化过程涉及以下步骤：(a)在惰性溶剂或溶剂混合物中提供吗啡成分的溶液或悬浮液；(b)在碱性成分存在的情况下，用甲基化剂对所得溶液或悬浮液进行甲基化处理；以及(c)将所得的可待因作为自由碱或盐进行回收。
• Chemical Compounds
  申请人：Brown Alan Daniel

  公开号：US20120010182A1

  公开（公告）日：2012-01-12

  The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new sulfonamide Nav1.7 inhibitors of formula (I): or pharmaceutically acceptable salts thereof, wherein Z 1 , R a , R b , R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.

  该发明涉及磺胺衍生物，其在医学上的应用，含有它们的组合物，其制备方法以及用于这些方法的中间体。 更具体地，该发明涉及公式（I）的新磺胺基Nav1.7抑制剂： 或其药学上可接受的盐，其中Z 1 ，R a ，R b ，R 1 ，R 2 ，R 3 ，R 4 和R 5 如描述中所定义。 Nav 1.7抑制剂在治疗各种疾病，特别是疼痛方面具有潜在用途。
• [EN] COMBINATIONS COMPRISING ALPHA-2-DELTA LIGANDS<br/>[FR] COMBINAISONS CONTENANT DES LIGANDS DE ALPHA-2-DELTA
  申请人：PFIZER LTD

  公开号：WO2005092318A1

  公开（公告）日：2005-10-06

  The instant invention relates to a combination, particularly a synergistic combination, of an alpha-2-delta ligand and an atypical antipsychotic, and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof and their use in the treatment of pain, particularly neuropathic pain.

  这项即时发明涉及一种组合，特别是α-2-δ配体和非典型抗精神病药物的协同组合，以及其药用盐、药物组合物及其在治疗疼痛，特别是神经病痛中的应用。