Nuciferine ((-)-Nuciferine) is an alkaloid found within the plants Nymphaea caerulea and Nelumbo nucifera. It has a profile of action associated with dopamine receptor blockade.

5-HT2C:131 nM, D4:2 μM (EC50), 5-HT2B:1 μM, D5:2.6 μM (EC50), 5-HT1A:3.2 μM (EC50), 5-HT6:700 nM(EC50), D2:64 nM (EC50), 5-HT2A:478 nM, 5-HT7:150 nM

Nuciferine在DD2受体上作为部分激动剂，其活性（Emax=67%的多巴胺）与阿立哌唑（Emax=50%的多巴胺）类似。根据其部分激动剂活性，Nuciferine能够抑制由多巴胺诱导的Gi激活，其效力与氯氮平相近（Nuciferine KB=62 nM; 氯氮平KB=20 nM），此通过Schild回归分析确定[1]。作为一种天然产品，Nuciferine能有效抑制成年蠕虫的活动性。Nuciferine可有效抑制成年血吸虫的基础及5-HT诱导的运动性。对于Sm.5HTRL和血吸虫幼虫，Nuciferine的抑制浓度分别为0.24±0.04 μM和0.62±0.22 μM[2]。

在与抗精神病化合物作用相关的啮齿动物模型中，Nuciferine阻断了头颈摆动反应和5-HT2A激动剂的辨别刺激效果，取代了氯氮平的辨别刺激，增强了安非他明引起的运动活性，抑制了苯环利定（PCP）引起的运动活性，并在不引起僵直的情况下挽救了PCP引起的前脉冲抑制中断。在1或3 mg/kg Nuciferine存在下，累积的PCP剂量产生的效果与单独使用PCP相似。在训练有识别氯氮平的动物中，10 mg/kg Nuciferine表现出对1.25 mg/kg氯氮平的剂量依赖性替代（80.63%的药物杠杆反应），其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）未能产生对氯氮平辨别线索的替代。除了在适当的氯氮平杠杆上有较高百分比的反应外，与对照组相比，10 mg/kg Nuciferine还显著抑制了反应速率（p<0.001）[1]。

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].

Nuciferine is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1]. 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].