Pitolisant hydrochloride is a potent and selective nonimidazole inverse agonist at the recombinant humanhistamine H3 receptor(K_i=0.16 nM).

Ki: 0.16 nM (H3 receptor)^[1]
EC50: 1.5 nM (H3 receptor)^[1]

On the stimulation of guanosine 5′-O-(3-[³⁵S]thio)triphosphate binding to this receptor, Pitolisant (BF2.649) behaves as a competitive antagonist with a K_ivalue of 0.16 nM and as an inverse agonist with an EC₅₀value of 1.5 nM and an intrinsic activity ~50% higher than that of ciproxifan. Pitolisant displaces [¹²⁵I]iodoproxyfan binding from mouse brain cortical membranes with an IC₅₀value of 26.4±4.5 nM. Taking into account the K_dvalue of the radioligand (161±9 pM), the deduced K_ivalue for Pitolisant is 14±1 nM. Pitolisant displaces [¹²⁵I]iodoproxyfan binding from membranes of rat glioma C6 cells stably expressing the human H₃receptor with an IC₅₀value of 4.2±0.2 nM. Taking into account the K_dvalue of the radioligand (50±4 pM), the deduced K_ivalue for Pitolisant is 2.7±0.5 nM. Pitolisant progressively reverses this response with a Hill coefficient close to unity and an IC₅₀value of 330±68 nM, leading to a K_ivalue of 17±4 nM. Pitolisant elicits a dose-dependent decrease of the basal-specific [³⁵S]GTPγS binding to membranes with a maximal effect corresponding to 75±1% of the basal-specific binding and an EC₅₀value of 1.5±0.1 nM^[1].

The administration of Pitolisantat a single dose of 10 mg/kg 30 min before a single dose of LY170053 (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 LY170053 2 mg/kg b.w., and again after 4 h LY170053 2 mg/kg b.w.) show that the administration of Pitolisant followed by that of LY170053 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]^[2]. 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^[3].

332.31

Solid

C₁₇H₂₇Cl₂NO

903576-44-3

替洛利生盐酸盐

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

H₂O : 100 mg/mL(300.92 mM;Need ultrasonic)

DMSO : ≥ 43 mg/mL(129.40 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： PBS

  Solubility: 50 mg/mL (150.46 mM); Clear solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (7.52 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.52 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (7.52 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.52 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。