| CAS |
No.475-83-2 |
| 中文名称 |
荷叶碱(10mM in DMSO,无菌） |
| 英文名称 |
Nuciferine(10mM in DMSO，Sterile） |
| 分子式 |
C19H21NO2 |
| 分子量 |
295.38 |
| 溶解性 |
请根据自己的实验要求使用。 |
| 外观(性状) |
无菌溶液 |
| 储存条件 |
Stroe at -20℃，6 months. |
| 运输条件 |
冷冻运输 |
| 靶点 |
5-HT Receptor |
| 通路 |
Neuronal Signaling;GPCR & G Protein |
| 背景说明 |
Nuciferine 是一种 5-HT2A，5-HT2C 和 5-HT2B 拮抗剂。 |
| 生物活性 |
Nuciferine is an antagonist at 5-HT2A (IC50=478 nM)， 5-HT2C (IC50=131 nM)， and 5-HT2B (IC50=1 μM)， an inverse agonist at 5-HT7 (IC50=150 nM)， a partial agonist at D2 (EC50=64 nM)， D5 (EC50=2.6 μM) and 5-HT6 (EC50=700 nM)， an agonist at 5-HT1A (EC50=3.2 μM) and D4 (EC50=2 μM) receptor.[1-2] |
| In Vitro |
Nuciferine 是 DD2 受体的部分激动剂，其活性 (Emax=67% of dopamine) 类似于 Aripiprazole (Emax=50 多巴胺的百分比）。 与其部分激动剂活性一致，Nuciferine 抑制多巴胺诱导的 Gi 激活，效力与 Clozapine 相似（Nuciferine KB=62 nM；Clozapine K B=20 nM) 通过 Schild 回归分析确定[1]。 天然产物 Nuciferine 可作为成虫蠕动的有效抑制剂。 Nuciferine 可有效抑制成年血吸虫的基础运动和 5-HT 诱发运动。 Nuciferine 分别以 0.24±0.04 和 0.62±0.22 μM 抑制 Sm.5HTRL 和血吸虫[2]。 |
| In Vivo |
在与抗精神病药物作用相关的啮齿动物模型中，Nuciferine 阻断 5-HT2A 激动剂的头部抽搐反应和辨别刺激作用，替代 Clozapine 的辨别刺激，增强苯丙胺诱导的运动活性，抑制 Phencyclidine (PCP)-诱导的运动活动，并挽救了 PCP 诱导的前脉冲抑制中断而不诱导强直性昏厥。在 1 或 3 mg/kg Nuciferine 存在的情况下，累积的 PCP 剂量产生与单独使用 PCP 相似的替代。在经过氯氮平训练的动物中，10 mg/kg Nuciferine (80.63% 的药物杠杆反应) 可观察到 1.25 mg/kg Clozapine 的剂量依赖性替代，ED50 值为 5.42 mg/kg (95% CI 3.09-9.48 mg/kg)，而测试的较低剂量 (0.1 mg/kg-3 mg/kg) 未能产生 Clozapine 的区分提示。与载体控制点相比，10 mg/kg Nuciferine 除了对 Clozapine 适当杠杆产生高比例的反应外，还产生显著的速率抑制 (p[1]。 |
| 细胞实验 |
Cells are plated into 48-well plates one day before uptake is performed. Cells are washed with 0.5 mL uptake buffer (4 mM Tris， 6.25 mM HEPES， 120 mM NaCl， 5 mM KCl， 1.2 mM CaCl2， 1.2 mM MgSO4， 5.6 mM D-glucose， 1.7 mM ascorbic acid， and 1 μM pargyline， pH 7.4). Cells are incubated with 225 μL uptake buffer with or without the indicated concentration of Nuciferine for 15 minutes. After incubation， 25 μL uptake buffer containing 3H-DA and DA is added for a final concentration of 20 nM 3H-DA and 1 μM DA. Cells are incubated at 37°C for 20 minutes or for the time indicated. Nonspecific uptake is determined in the presence of 10 μM nomifensine. Uptake is terminated by aspirating uptake buffer and washing each well twice with 0.5 mL ice-cold uptake buffer. Cells are lysed in 0.1 N NaOH and transferred to vials containing 3 mL scintillation cocktail. Radioactivity is quantitated using a Beckman LS6500 counter. Data are analyzed in Graph Pad Prism 5.0[1]. |
| 动物实验 |
Mice[1] Adult male NIH Swiss mice weighing approximately 25 g are used. Mice are injected with either Nuciferine (1， 3， or 10 mg/kg， i.p.) or vehicle， n=4 mice/condition. Fifteen minutes later， mice are injected with 1 mg/kg DOI (i.p.) and immediately placed in an observation chamber (new cage without bedding). Head-twitches (operationally defined as a rapid rotational jerk of the head that can be distinguished from species-appropriate grooming or scratching behaviors) are counted for 20 minutes in 5 minute bins. For the time-course study， mice are pretreated with 3.0 mg/kg Nuciferine (i.p.) at 60， 45， 30， 15， or 0 minutes (co-injection) prior to the 1.0 mg/kg DOI (i.p.) injection， and head-twitches are counted as described above. In one experiment， mice (n=4 per condition) are pretreated with an injection (s.c.) of 3.0 mg/kg Nuciferine or vehicle 15 minutes prior to 1.0 mg/kg DOI injection (i.p.) and head-twitches are counted as described above. All experiments are performed by 3 observers， with 2 observers blinded to the experimental conditions which are evenly distributed. Power analyses are performed with the resulting data. The two highest doses of Nuciferine tested (10 and 3 mg/kg)， had 0.96 and 0.88 power to detect significance (α=0.05). As these experiments are performed blinded and in distinct mice， further replication is not performed. |
| 激酶实验 |
For affinity determination， Nuciferine is subjected to primary radioligand binding assays tested at a single 10 μM concentration to displace 50% of the radioligand at a given receptor target. If a more than 50% of the radioligand is displaced， Nuciferine is selected for a secondary binding assay tested at 11 concentrations in triplicate in competition with the radioligand to generate an IC50 and Ki. Binding assays are performed in 96-well plates with 125 μL per well in appropriate binding buffer using radioligand at or near the Kd. Plates are incubated at room temperature in the dark for 90 min. Reactions are stopped by vacuum filtrations onto 0.3% polyethyleneimine soaked 96-well filter mats using a 96-well Filtermate harvester， followed by at least three washes of cold wash buffer. Scintillation cocktail is melted onto dried filters and radioactivity is counted using a Wallac Trilux Microbeta[1]. |
| 数据来源文献 |
[1]. Farrell MS， et al. In Vitro and In Vivo Characterization of the Alkaloid Nuciferine. PLoS One. 2016 Mar 10;11(3):e0150602.
[2]. Chan JD， et al. Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist. Int J Parasitol Drugs Drug Resist. 2016 Dec;6(3):364-370. |
| 规格 |
1ml |
| 单位 |
瓶 |
中文
英语
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