methyl (15R,18S,20R)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyl)oxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate,hydrochloride | 1263-59-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 育亨宾生物碱
• 英文名称: methyl (15R,18S,20R)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyl)oxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate,hydrochloride
• 英文别名: 11,17α-dimethoxy-18β-(3,4,5-trimethoxy-benzoyloxy)-20α-yohimban-16β-carboxylic acid methyl ester; hydrochloride；11,17α-Dimethoxy-18β-(3,4,5-trimethoxy-benzoyloxy)-20α-yohimban-16β-carbonsaeure-methylester; Hydrochlorid
• CAS: 1263-59-8；16994-56-2；107928-28-9
• 化学式: C₃₃H₄₀N₂O₉*ClH
• 分子量: 645.15
• InChiKey: ZYWIWGUMKCZKOO-ZCOPZROHSA-N

物化性质

• 溶解度：
  DMSO 中≥25 mg/mL；不溶于水；温和加热和超声波下，乙醇中≥2.74 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.59
• 重原子数：
  45.0
• 可旋转键数：
  8.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  117.78
• 氢给体数：
  1.0
• 氢受体数：
  10.0

制备方法与用途

生物活性

Reserpine (hydrochloride) 是囊泡单胺转运蛋白 2 (VMAT2) 的抑制剂。

靶点

VMAT2

体外研究

Reserpine hydrochloride is an inhibitor of the vesicular monoamine transporter 2 (VMAT2). Reserpine hydrochloride displays a significant on the density of dopamine D1 receptors (F _2,12 =8.81, p<0.01) in the rat striatum. The affinity (Kd) for the dopamine D1 and D2 receptors during withdrawal from acute and chronic administration of reserpine is not change. IC ₅₀ values of 43.9 and 54.9 μM are obtained after 1 day of treatment with Reserpine hydrochloride in JB6 P+ and HepG2-C8 cells, respectively. Reserpine hydrochloride induces luciferase activity in a dose-dependent manner at concentrations ranging from 5 to 50 μM, and no significant induction is observed at concentrations lower than 5 μM. Results demonstrate that Reserpine hydrochloride (2.5 to 10 μM) also increases the protein expression of Nrf2, HO-1, and NQO1. Reserpine hydrochloride at concentrations of 2.5 to 10 μM decreases the mRNA expression of DNMT1, DNMT3a, and DNMT3b in a concentration-dependent manner in JB6 P+ cells after 7 days of treatment. Reserpine hydrochloride at 10 μM generates a significant difference for DNMT3a expression (p<0.05).

体内研究

Withdrawal (48 h) from chronic (14-day) but not acute Reserpine hydrochloride administration in a dose of 0.2 mg/kg i.p. produces a significant reduction of the immobility time (F _2,18 =3.68, p<0.05), but increases the climbing time (F _2,18 =4.48, p<0.02), and does not change the swimming time (F _2,18 =1.78; NS) in the forced swim test (FST) in rats. Reserpine hydrochloride at a dose of 5 mg/kg body weight produces significant increase in the urinary excretion profile of vanillylmandelic acid (VMA) compare to control animals. The amount of 5-hydroxyindoleacetic acid (5-HIAA) excreted in animals treated with Reserpine is found to be more than in the control. Dose dependent hypotension is observed with Reserpine hydrochloride. Reserpine hydrochloride at doses of 0.5, 1, 5, 10 and 15 μg/kg produce significant (p<0.01) reduction in blood pressure compare to control.