Scopolamine methyl nitrate | 6106-46-3

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: Scopolamine methyl nitrate
• 英文别名: [(1S,2S,4R,5R)-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonan-7-yl] (2S)-3-hydroxy-2-phenylpropanoate;nitrate
• CAS: 6106-46-3
• 化学式: C18H24N2O7
• 分子量: 380.4
• InChiKey: BSQIVYOSLFLSGE-OZVSTBQFSA-N

物化性质

• 熔点：
  199 °C
• 物理描述：
  Odorless, white crystalline powder.
• 颜色/状态：
  WHITE CRYSTALLINE POWDER
• 气味：
  ODORLESS
• 味道：
  TASTELESS
• 溶解度：
  FREELY SOL IN WATER, DIL ALC; SLIGHTLY SOL IN ABS ALC

计算性质

• 辛醇/水分配系数(LogP)：
  0.82
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

毒理性

• 人类毒性摘录

在正常人群中，皮下注射1毫克已导致持续数小时的瞳孔扩大和眼肌麻痹，但是0.5毫克皮下或肌肉注射对调节力几乎没有影响，而口服16毫克没有任何效果。

IN NORMAL PEOPLE SC INJECTION OF 1 MG HAS CAUSED MYDRIASIS & CYCLOPLEGIA LASTING SEVERAL HR, BUT 0.5 MG SC OR IM HAS HAD LITTLE OR NO EFFECT ON ACCOMMODATION, & 16 MG ORALLY HAS HAD NO EFFECT.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

在老鼠腹腔内注射东莨菪碱甲基硝酸盐（不易透过血脑屏障）1毫克/千克，并未显著损害条件性抑制反应的习得。这表明东莨菪碱对条件性抑制习得的中断效果是由于其中枢作用。

ADMINISTRATION OF SCOPOLAMINE METHYLNITRATE (WHICH DOES NOT READILY PENETRATE THE BRAIN) 1 MG/KG INTRAPERITONEALLY TO RATS DID NOT SIGNIFICANTLY IMPAIR THE ACQUISITION OF THE CONDITIONED SUPPRESSION RESPONSE. THIS INDICATED THAT THE DISRUPTIVE EFFECTS OF SCOPOLAMINE ON THE ACQUISITION OF CONDITIONED SUPPRESSION ARE DUE TO CENTRAL ACTION.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验中训练老鼠从8臂放射状迷宫的每个臂的末端获取食物颗粒。基线表现特征是很少进入已经获取过食物颗粒的臂。无论是腹腔注射硫酸右旋安非他命（0.1-3.0 mg/kg）还是戊巴比妥钠（1.0-10.0 mg/kg）都没有影响选择准确性，尽管在注射右旋安非他命后臂进入的速度增加，而在注射戊巴比妥钠后速度降低。氢溴酸东莨菪碱（0.1-1.0 mg/kg）减少了准确性和臂进入的速度。硝酸甲基东莨菪碱（0.17, 1.0 mg/kg）对表现的影响很小。

Rats were trained to obtain food pellets from the end of each arm of an 8-arm radial maze. Baseline performance was characterized by very few entries into arms from which the food pellet had already been obtained. Neither ip d-amphetamine sulfate (0.1-3.0 mg/kg) nor pentobarbital Na (1.0-10.0 mg/kg) affected choice accuracy, although the rate of arm-entry increased after d-amphetamine and decreased after pentobarbital Na. Scopolamine-HCl (0.1-1.0 mg/kg) reduced both accuracy and the rate of arm entry. Methylscopolamine nitrate (0.17, 1.0 mg/kg) had little effect on performance.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

长期给雌性大鼠注射硝酸甲酯东莨菪碱，剂量远大于阻断迷走神经介导的胰岛素分泌所需剂量，仅能减少腹内侧下丘脑肥胖31%。即使在最初有效剂量（0.15毫克/千克，每日四次）增加八倍时，至少仍有59%的肥胖持续存在。更高剂量也不能预防腹内侧下丘脑损伤后的体重增加，即使在损伤前就开始使用东莨菪碱治疗。损伤后10天，减慢的胃肠道蠕动显然阻止了进一步的体重增加。

Chronic administration of scopolamine methyl nitrate /to female rats/, at doses much greater than required to block vagally mediated insulin secretion, reduced static phase ventromedial hypothalamus obesity by only 31%. At least 59% of the obesity persisted even when the initially effective dose (0.15 mg/kg, 4 times/day) was increased eight-fold. The larger dose also did not prevent ventromedial hypothalamus and weight gain when scopolamine treatment was begun before the lesion. By 10 days after the lesion, reduced gastrointestinal motility apparently prevented further weight gain.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1
• 危险品标志：
  T
• 安全说明：
  S25,S36/37/39,S45
• 危险类别码：
  R23/24/25
• WGK Germany：
  3
• 危险品运输编号：
  UN 1544 6.1/PG 3

反应信息

• 作为反应物：
  描述：

  (-)-2-氨基-5-膦酰戊酸 、 1-(4-氨基苯基)-3-甲基氨基甲酰-4-甲基-7,8-亚甲基二氧基-3,4-二氢-5H-2,3-苯并二氮杂革 、 (2S,4R)-4-methylglutamic acid 、 (2S,2R,3R)-2-(2,3-二甲基环丙基)甘氨酸 、 环噻嗪 、 [3H]-UBP 310 、 Scopolamine methyl nitrate 、 盐酸毛果芸香碱 、 地西泮 生成 4-[6-amino-3-(4-methoxyphenyl)pyridazin-1-ium-1-yl]butanoate
  参考文献：
  名称：

  Method and Pharmaceutical Composition for use in the Treatment of Epilepsy

  摘要：

  本发明涉及一种化合物，其是GluK2/GluK5受体的拮抗剂或GluK2/GluK5受体表达的抑制剂，可用于治疗或预防癫痫。

  公开号：

  US20160228439A1

文献信息

• Method and Pharmaceutical Composition for use in the Treatment of Epilepsy
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：US20160228439A1

  公开（公告）日：2016-08-11

  The present invention relates to a compound which is an antagonist of the GluK2/GluK5 receptor or an inhibitor of the GluK2/GluK5 receptor expression for use in the treatment or the prevention of epilepsy.

  本发明涉及一种化合物，其是GluK2/GluK5受体的拮抗剂或GluK2/GluK5受体表达的抑制剂，可用于治疗或预防癫痫。