生物活性
Pimavanserin(ACP-103)是5-HT2A高效选择性激动剂，细胞功能水平测得pIC50均值为8.7。Pimavanserin displays nanomolar potency as a 5-HT2A receptor inverse agonist, selectivity for 5-HT2A over 5-HT2C receptors, and no meaningful activity at any other G-protein coupled receptor. Pimavanserin demonstrates robust activity in preclinical models of schizophrenia and PDP, and do not worsen motoric symptoms, in contrast to the APDs tested. Pimavanserin showes highly significant benefits in the primary endpoint, the scale for assessment of positive symptoms-PD, a scale adapted for use in PDP. Pimavanserin is safe and well-tolerated with long-term use.
化学数据
| 分子量 | 427.55 |
| 分子式 | C25H34FN3O2 |
| CAS号 | 706779-91-1 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO 10 mM |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | NIH-3T3 cells |
| 方法 | Receptor Selection and Amplification Technology.
In brief, NIH-3T3 cells were grown to 80% confluence in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% bovine calf serum (Hyclone Laboratories, Logan, UT) and 1% penicillin/streptomycin/glutamine (Invitrogen, Carlsbad, CA). Cells were transfected in roller bottles for 18 h with the relevant G protein-coupled receptor gene and the gene for β-galactosidase. After transfection, cells were trypsinized, harvested, and frozen. Aliquots of frozen cell batches were thawed and tested for response to reference agonists and inverse agonists ensuring pharmacologically appropriate responses. To initiate an assay, cells were thawed rapidly and prepared in DMEM contained 0.4% calf serum (Hyclone Laboratories), 30% UltraCulture (BioWhittaker, Rockland, ME), and 1% penicillin/streptomycin/glutamine, and then they were added to half-area 96-well microtiter plates containing either test compounds or reference ligands. After 5 days in culture, media were removed from the wells, and the cells were incubated at room temperature in 200 μl of phosphate-buffered saline, pH 7.4, with 3.5 mM o-nitrophenyl-β-d-galactopyranoside (Sigma-Aldrich, St. Louis, MO) and 0.5% Nonidet P-40 (Sigma-Aldrich). After 2 to 4 h, the plates were read at 420 nm on a plate-reader (Bio-Tek Instruments, Winooski, VT). |
| 浓度 | 0~10 μM |
| 处理时间 | 5 days |
| 动物实验 |
|---|
| 动物模型 | DOI head-twitch experiments in rats and Non-Swiss albino mice |
| 配制 | 0.9% saline |
| 剂量 | 1, 3 or 10 mg/kg |
| 给药处理 | s.c. or p.o. |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3389 mL | 11.6945 mL | 23.3891 mL |
| 5 mM | 0.4678 mL | 2.3389 mL | 4.6778 mL |
| 10 mM | 0.2339 mL | 1.1695 mL | 2.3389 mL |
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