Orvepitant maleate (GW823296 maleate) 是一种有效，选择性，口服活性且耐受性良好的neurokinin-1 (NK-1)受体拮抗剂，对人neurokinin-1受体的pKi为 10.2。Orvepitant maleate 可以穿越血脑屏障。Orvepitant maleate 可用于抑郁症和慢性顽固性咳嗽的研究。
| 生物活性 | Orvepitant maleate (GW823296 maleate) is potent, selective, orally active and well-toleratedneurokinin-1 receptor (NK-1)antagonist with apKiof 10.2 forhuman neurokinin-1 receptor. Orvepitant maleate can across the blood-brain barrier. Orvepitant maleate has the potential for depressive disorder and chronic refractory cough (CRC) treatment[1][2]. |
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体外研究
(In Vitro) | Orvepitant (Compound 3a) is further characterized in terms of the ability to functionally inhibit substance P (SP)-induced release of cytosolic Ca2+in human neurokinin-1 receptor (hNK1)-CHO cells. Orvepitant (0.3-10 nM), pre-incubated for 1 h at 37℃ before adding the agonist SP, produces a non-surmountable antagonism of agonist concentration-response curve. For Orvepitant apparents pKBvalue of 10.30[1].
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体内研究
(In Vivo) | Orvepitant (Compound 3a; 0.3-10 mg/kg; Oral administration; marmoset) treatment shows a dose dependant reduction of the number of postures was observed at 1 mg/kg (34.9% reduction), 3 mg/kg (36.6% reduction) and 10 mg/kg (46.4% reduction), suggesting a potential anxiolytic-like effect of the compound[1].
Orvepitant (compound 3a) shows an oral bioavailability (F) of 17% in rat and 55% in dog, plasma clearance (Clp) of 29 mL/min/kg in rat and 6 mL/min/kg in dog and a half-life of 2.3 h in rat and 6.1 h in dog. As far as the brain penetration in rats is concerned, a B/P ratio of 1.2 is observed 5 min after the i.v. administration of a 1 mg/kg dose of Orvepitant[1].
| Animal Model: | Human threat test in the marmoset (HTT)[1] | | Dosage: | 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg | | Administration: | Oral administration | | Result: | A dose dependant reduction of the number of postures was observed at 1 mg/kg (34.9% reduction), 3 mg/kg (36.6% reduction) and 10 mg/kg (46.4% reduction). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 30 mg/mL(40.28 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.3428 mL | 6.7141 mL | 13.4282 mL | | 5 mM | 0.2686 mL | 1.3428 mL | 2.6856 mL | | 10 mM | 0.1343 mL | 0.6714 mL | 1.3428 mL |
*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。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 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： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 5 mg/mL (6.71 mM); Clear solution
此方案可获得 ≥ 5 mg/mL (6.71 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 50.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 5 mg/mL (6.71 mM); Clear solution
此方案可获得 ≥ 5 mg/mL (6.71 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 50.0 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 5 mg/mL (6.71 mM); Clear solution
此方案可获得 ≥ 5 mg/mL (6.71 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 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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