PITOLISANT

中文名称:

PITOLISANT

中文同义词:

替洛利生;1-[3-[3-(4-氯苯基)丙氧基]丙基]哌啶

英文名称:

Piperidine, 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-

英文同义词:

Piperidine, 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-;PITOLISANT;1-[3-[3-(4-Chlorophenyl)propoxy]propyl]piperidine;3-(4-Chlorophenyl)propyl 3-piperidinopropyl ether;Tiprolisant;Tirolisant;Pitolisant (BF2.649);TIPROLISANT;BF-2649;BF 2.649

CAS号:

362665-56-3

分子式:

C17H26ClNO

分子量:

295.85

EINECS号:

相关类别:

G蛋白偶联受体G蛋白;定制产品;陕西林奈主打产品;API

Mol文件:

362665-56-3.mol

沸点 

398.7±32.0 °C(Predicted)

密度 

1.056

酸度系数(pKa)

9.41±0.10(Predicted)

生物活性

Pitolisant 是一种有效的选择性的非咪唑类重组人组胺 H3 受体反相激动剂，Ki 为 0.16 nM。

靶点

Ki: 0.16 nM (H3 receptor) EC50: 1.5 nM (H3 receptor)

体外研究

On the stimulation of guanosine 5′-O-(3-[ 35 S]thio)triphosphate binding to this receptor, Pitolisant (BF2.649) behaves as a competitive antagonist with a K i value of 0.16 nM and as an inverse agonist with an EC 50 value of 1.5 nM and an intrinsic activity ~50% higher than that of ciproxifan. Pitolisant displaces [ 125 I]iodoproxyfan binding from mouse brain cortical membranes with an IC 50 value of 26.4±4.5 nM. Taking into account the K d value of the radioligand (161±9 pM), the deduced K i value for Pitolisant is 14±1 nM. Pitolisant displaces [ 125 I]iodoproxyfan binding from membranes of rat glioma C6 cells stably expressing the human H 3 receptor with an IC 50 value of 4.2±0.2 nM. Taking into account the K d value of the radioligand (50±4 pM), the deduced K i value for Pitolisant is 2.7±0.5 nM. Pitolisant progressively reverses this response with a Hill coefficient close to unity and an IC 50 value of 330±68 nM, leading to a K i value of 17±4 nM. Pitolisant elicits a dose-dependent decrease of the basal-specific [ 35 S]GTPγS binding to membranes with a maximal effect corresponding to 75±1% of the basal-specific binding and an EC 50 value of 1.5±0.1 nM.

体内研究

The administration of Pitolisantat a single dose of 10 mg/kg 30 min before a single dose of Olanzapine (2 mg/kg b.w.) also significantly affects immobility time in the FST. Subsequent administration of the aforementioned drug sequence in mice statistically significantly increases the duration of immobility in comparison to the time determined in the control group in the FST. It decreased locomotor activity as well. In contrast, the results obtained in subchronic treatment after fifteen administrations of both drugs (Pitolisant 10 mg/kg b.w., and after 30 min Olanzapine 2 mg/kg b.w., and again after 4 h Olanzapine 2 mg/kg b.w.) show that the administration of Pitolisant followed by that of Olanzapine equalized the locomotor activity in mice; in comparison to the level of motility in the control group, to which only Pitolisant is administered. More importantly, this combination of drugs significantly reduces immobility time to the level obtained in the control group in the forced swim test in mice [one-way ANOVA; F (3,20) =4.226,P=0.0181]. Rats given Pitolisant (10 mg/kg) during the conditioning phase stayed 502±94 s on the paired texture, a value not statistically different from that of controls, indicating that Pitolisant did not support place preference.