CI-966 是一种有效，选择性，具有口服活性和可透过血脑屏障的 GABA 转运蛋白GAT-1抑制剂，抑制hGAT-1和rGAT-1的IC50分别为 0.26 μM 和 1.2 μM。CI-966 对 GAT-1 的选择性比 GAT-2，GAT-3 和 BGT-3 高 200 倍以上。CI-966 具有抗惊厥和神经保护活性。
| 生物活性 | CI-966 is a potent, selective, orally active and brain-penetrant inhibitor of the GABA transporterGAT-1, withIC50s of 0.26 μM and 1.2 μM forhGAT-1,rGAT-1, respectively. CI-966 shows more than 200-fold selectivity over GAT-2, GAT-3, and BGT-3. CI-966 exhibits anticonvulsant and neuroprotective activities[1][2][3]. |
| IC50& Target | IC50: 0.26 μM (hGAT-1); 1.2 μM (rGAT-1); 297 μM (rGAT-2); 333 μM (hGAT-3); 1140 μM (rGAT-3); 300 μM (hBGT-3)[1] |
体外研究
(In Vitro) | CI-966 functions by selectively inhibiting GABA reuptake in neurons and glial cells[4].
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体内研究
(In Vivo) | CI-966 produces intermediate levels of Pentylenetetrazol (PTZ)-lever responding when administered to PTZ-trained rats[4].
CI-966 enhances gamma-aminobutyric acid action in CA1 pyramidal layer in situ. CI-966 is administered systemically by i.p. injection (5 mg/kg) in Sprague-Dawley rats under urethane anaesthesia. Twenty to thirty minutes after injection there is a highly variable, but overall significant, enhancement of the inhibition of hippocampal population spikes by GABA applied by microiontophoresis in the CA1 region[5].
CI-966 exhibits anticonvulsant properties in various animal models. Oral absorption of CI-966 in dogs given 1.39 mg/kg is rapid with a tmaxof 0.7 hr.
In rats given 5 mg/kg oral, a mean tmaxof 4.0 hr is observed. Following i.v. administration of the same respective doses, elimination t1/2in dogs and rats averages 1.2 and 4.5 hr. Absolute oral bioavailability of CI-966 is 100% in both species[6].
| Animal Model: | Eight male Sprague-Dawley rats[4] | | Dosage: | 0.3-30 mg/kg | | Administration: | Injection IP in a volume of 1 mL/kg | | Result: | Dose dependent decreases in rates of responding occurred following CI-966 administration. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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