3-Veratroylveracevine | 71-62-5

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3-Veratroylveracevine
• 英文别名: (1,10,11,12,14,23-hexahydroxy-6,10,19-trimethyl-24-oxa-4-azaheptacyclo[12.12.0.02,11.04,9.015,25.018,23.019,25]hexacosan-22-yl) 3,4-dimethoxybenzoate
• CAS: 71-62-5
• 化学式: C₃₆H₅₁NO₁₁
• 分子量: 673.8
• InChiKey: FVECELJHCSPHKY-UHFFFAOYSA-N

物化性质

• 熔点：
  180℃
• 比旋光度：
  D20 +8.0° (ethanol)
• 沸点：
  689.74°C (rough estimate)
• 密度：
  1.45±0.1 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  乙醇：50 mg/mL
• 颜色/状态：
  YELLOWISH-WHITE, AMORPHOUS POWDER
• 旋光度：
  SPECIFIC OPTICAL ROTATION @ 20 °C/D (ETHANOL)= +8.0 DEG

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  48
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  179
• 氢给体数：
  6
• 氢受体数：
  12

ADMET

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

VERATRIDINE 对不同外钙离子存在时完整淡水龙虾( PROCAMBARUS CLARKI )轴突静息膜电位的影响。

THE ACTION OF VERATRIDINE ON THE RESTING MEMBRANE POTENTIAL OF INTACT CRAYFISH (PROCAMBARUS CLARKI) AXONS IN THE PRESENCE OF DIFFERENT EXTRACELLULAR ALKALINE-EARTH CATIONS WERE STUDIED USING INTRACELLULAR MICROELECTRODES. AT EXTRACELLULAR PH VALUES OF 7, 6, & 5, THE APPARENT BINDING SEQUENCE WAS CA2+ GREATER THAN OR EQUAL TO SR2+ MORE THAN MG2+ APPROX BA2+.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

从藜芦中提取的十一种生物碱对乌贼和淡水蟹巨轴突的膜电位和电导率的影响进行了比较。它们可以分为三类。1）藜芦碱、藜芦定碱和藜芦原碱A和B会导致膜去极化。效力按此顺序降低，藜芦碱和藜芦定碱产生50%最大去极化所需的浓度分别估计为3.3 x 10-5 M和3.7 x 10-3 M。藜芦碱的去极化主要是由于静息状态下膜对钠的透性选择性增加，并且可以被四环素毒素拮抗。所有这些都能有效增强并延长负（去极化）后电位。2）藜芦胺、异藜芦定碱、木藜芦定碱（5-藜芦烷-3-β, 11-α-二醇-11-醋酸酯）和5-藜芦烷-3α-11α-二醇（1x10-4）能够阻断动作电位，几乎没有或没有去极化。5-藜芦烷-3-β, 11-α-二醇阻断钠和钾电导率的增加。3）环戊胺、藜芦定碱、藜芦定碱和藜芦定碱对静息电位和动作电位没有影响。这些效果的可能的构效关系进行了讨论。

Eleven alkaloids obtained from Veratrum have been compared for their effects on the membrane potential and conductances of squid and crayfish giant axons. They can be classed in three groups. 1) Veratridine, cevadine and protoveratrines A and B cause the membrane to depolarize. The potency decreases in that order, and the concentrations of veratridine and cevadine required for 50% maximum depolarization are estimated to be 3.3 x 10-5 M and 3.7 x 10-3 M, respectively. The depolarization by veratridine is due primarily to a selective increase in resting sodium permeability of time membrane and is antagonized by tetrodotoxin. All of them are effective in augmenting and prolonging the negative (depolarizing) afterpotential. 2) Veratramin, eisorubijervine, muldaimine (5-veratranine 3-beta, 11-alpha-diol-11-acetate) and 5-veratranine-3alpha-11alpha-diol (1x10-4) re capable of blocking the action potential with little or no depolarization. 5-Veratranine-3-beta, 11-alpha-diol blocks both sodium and potassium conductance increases. 3) Cyclopamine, jervine, rubijervine and veratrosine have no effect on the resting and action potentials. Possible structure-activity relationships for these effects are discussed.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

1X10-4摩尔的外部应用到乌贼轴突的藜芦碱导致膜的去极化。在初始去极化期间，由单一刺激引发的重复后放电随着膜的进一步去极化和动作电位的阻断而逐渐减少。去极化主要是由于膜静息钠渗透性的增加。

1X10-4 MOLAR VERATRIDINE APPLIED EXTERNALLY TO SQUID AXON CAUSED DEPOLARIZATION OF MEMBRANE. DURING INITIAL DEPOLARIZATION, REPETITIVE AFTERDISCHARGES INITIATED BY SINGLE STIMULUS SUBSIDED AS MEMBRANE FURTHER DEPOLARIZED & ACTION POTENTIAL BLOCKED. DEPOLARIZATION IS DUE PRIMARILY TO INCR IN RESTING SODIUM PERMEABILITY OF MEMBRANE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

VERATRIDINE CAUSED DEPOLARIZATION OF EXCITABLE CELLS & PRODUCED MARKED ELEVATION OF ADENOSINE 3',5'-MONOPHOSPHATE (CYCLIC AMP) & GUANOSINE 3',5'-MONOPHOSPHATE (CYCLIC GMP) LEVELS IN INCUBATED SLICES OF MOUSE CEREBRAL CORTEX. 维腊酸导致可兴奋细胞的去极化，并在培养的小鼠大脑皮层切片中显著提高了腺苷3',5'-单磷酸（环磷酸腺苷）和鸟苷3',5'-单磷酸（环磷酸鸟苷）的水平。

VERATRIDINE CAUSED DEPOLARIZATION OF EXCITABLE CELLS & PRODUCED MARKED ELEVATION OF ADENOSINE 3',5'-MONOPHOSPHATE (CYCLIC AMP) & GUANOSINE 3',5'-MONOPHOSPHATE (CYCLIC GMP) LEVELS IN INCUBATED SLICES OF MOUSE CEREBRAL CORTEX.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

给定的数据用于评估脂溶性、与人类白蛋白的结合以及口服给药后人体的尿排泄。讨论了结构-活性关系，包括脂溶性和药理性质。

DATA GIVEN FOR LIPID SOLUBILITY, BINDING TO HUMAN ALBUMIN, & URINARY EXCRETION AFTER ORAL ADMIN TO HUMANS. STRUCTURE-ACTIVITY CORRELATIONS ARE DISCUSSED WITH RESPECT TO LIPID SOLUBILITY & PHARMACOLOGICAL PROPERTIES.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T+
• 安全说明：
  S26,S28,S36/37,S36/37/39,S45,S61
• 危险类别码：
  R26/27/28
• WGK Germany：
  2
• RTECS号：
  YX5600000
• 海关编码：
  2929101000
• 包装等级：
  II
• 危险类别：
  6.1(a)
• 危险品运输编号：
  UN 1544 6

制备方法与用途

生物活性

Veratridine（3-Veratroylveracevine）是一种来自百合科植物的生物碱，是一种钠通道激动剂。它能够抑制Nav1.7的峰值电流，IC50值为18.39 μM。

类别

有毒物品

毒性分级

剧毒

急性毒性

• 大鼠腹腔LD50：3.5毫克/公斤
• 小鼠腹腔LD50：1.35毫克/公斤

可燃性危险特性

可燃，火场排出含氮氧化物、辛辣刺激烟雾。

储运特性

库房应低温、通风、干燥；与食品原料分开存放。

灭火剂

水、二氧化碳、干粉、砂土。

文献信息

• Reduced Toxicity Methotrexate Formulations and Methods for Using the Same
  申请人：Fogarty Patrick

  公开号：US20080312201A1

  公开（公告）日：2008-12-18

  Methods of using methotrexate (MTX) active agents in which reduced host toxicity is observed are provided. In the subject methods, an effective amount of an MTX active agent is administered to the host in conjunction with the administration of an MTX toxicity reducing agent of the present invention. Also provided are compositions for use in practicing the subject methods, e.g., pharmaceutical compositions having reduced toxicity, in which the MTX active agent is combined with an MTX toxicity reducing agent that reduces the level of undesired MTX toxicity while maintaining an effective MTX anti-proliferative activity. Also provided are methods of using the subject methods and compositions in the treatment of a variety of different disease conditions.