Basmisanil (RG1662) 是一种高选择性含 α 亚基 GABAA 受体 (GABAAα5) 的负变构调节剂，具有口服活性。Basmisanil 可以抑制 GABAA-α5，Ki值为 5 nM 和IC50值为 8 nM。Basmisanil 可用于多种认知和精神障碍的研究。
| 生物活性 | Basmisanil (RG1662) is a highly selective orally activeα subunit-containing GABAA receptors (GABAAα5)negative allosteric modulator (NAMs). Basmisanil can inhibit GABAA-α5 with aKivalue of 5 nM andIC50value of 8 nM, respectively. Basmisanil can be used for the research of multiple cognitive and psychiatric disorders[1]. |
| IC50& Target | IC50: 8 nM (GABAAα5)
Ki: 5 nM (GABAAα5); 1031 nM (GABAAα1); 458 nM (GABAAα2); 510 nM (GABAAα3) |
体外研究
(In Vitro) | Basmisanil (0.1 nM-100 μM) has high affinity for bounding to recombinant human GABAA-α5 receptors with a Kivalue of 5 nM and more than 90-fold selectivity versus α1 (Ki= 1031 nM), α2 (Ki= 458 nM), and α3 (Ki= 510 nM) subunit-containing receptors[1].
Basmisanil (1 nM-1 μM) shows a highly selective inhibition of GABAA-α5 with a IC50value of 8 nM[1].
Basmisanil (1 μM) inhibits GABA-induced currents at GABAA-α5 yet had little or no effect at the other receptor subtypes[1].
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体内研究
(In Vivo) | Basmisanil (3-100 mg/kg, p.o.) occupies GABAA-α receptor in dose-dependent in rat brain[1].
Basmisanil (3-600 mg/kg p.o.) improves cognition in rats and non.human primates and not show anxiogenic or proconvulsant effects[1].
| Animal Model: | Sprague Dawley rats[1]
(180 g; female) | | Dosage: | 3-100 mg/kg | | Administration: | p.o. | | Result: | Decreased the binding of [3H]-Ro 15-4513 in a dose-dependent manner.
Reduced specific binding in the hippocampus by 70% at the highest dose (100 mg/kg). |
| Animal Model: | Lister Hooded rats, Wistar rats and F-344 Fischer rats[1]
(Lister Hooded rats: 220-250 g; male)
(Wistar rats: 200-220 g; male and female)
(F-344 Fischer rats: 170-180 g; male) | | Dosage: | 3-600 mg/kg | | Administration: | p.o. | | Result: | Significantly attenuated the diazepam-induced deficit.
Showed plasma concentrations in dose- and time-dependent manner and reached a maximal level of 903 ng/mL (379 nM free plasma) 30 min after the administration at 10 mg/kg. |
| Animal Model: | Male cynomolgus macaques[1]
(Macaca fascicularis; 7-10 kg) | | Dosage: | 1-600 mg/kg | | Administration: | p.o. | | Result: | Significantly improved the percentage of correct first reaches during difficult trials of the object retrieval task at the 3 and 10 mg/kg doses.
Exhibited an inverted U-shaped dose response in this paradigm with the 1 and 30 mg/kg doses producing no marked improvement on performance.
Increased the total plasma exposure in dose-dependent. |
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| Clinical Trial | |
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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 : 100 mg/mL(224.49 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.2449 mL | 11.2244 mL | 22.4487 mL | | 5 mM | 0.4490 mL | 2.2449 mL | 4.4897 mL | | 10 mM | 0.2245 mL | 1.1224 mL | 2.2449 mL |
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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: ≥ 2.5 mg/mL (5.61 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.61 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 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: ≥ 2.5 mg/mL (5.61 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.61 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (5.61 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.61 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。 *以上所有助溶剂都可在本网站选购。
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