| 名稱 | Nefiracetam |
| 描述 | Nefiracetam (DM9384) are underway in Phase 2 trials. Nefiracetam, a GABAergic、 cholinergic、and monoaminergic neuronal system enhancer, is used for Ro 5-4864-induced convulsions. |
| 細(xì)胞實(shí)驗(yàn) | The injected oocytes are transferred to the recording chamber 24 to 48 hours after incubation and continuously superfused at room temperature (20 to 22 °C) in a standard frog Ringer's solution (115 mM NaCl, 2 mM KCl, 1.8 mM CaCl2, and 5 mM HEPES, pH 7.0). Ca2+ -free extracellular solution consisted of 115 mM NaCl, 2 mM KCl, 5 mM MgCl2, 5 mM HEPES, and 1 mM EGTA, pH 7.0. To remove the effect of the muscarinic ACh receptor, 1 μM atropine is added to the extracellular solution. ACh-activated currents are recorded using two-electrode, voltage-clamp techniques. The currents are analyzed on a microcomputer using pClamp software. ACh is bath-applied to oocytes. Nefiracetam is dissolved in distilled water at 1 mM for stock solution and diluted into concentrations required with the extracellular solution. (Only for Reference) |
| 激酶實(shí)驗(yàn) | Assay of glutamate released: Hippocampal slices (400 μM) are prepared from the guinea pig brain using standard techniques. A slice is fixed on a pair of silver wire electrodes (10 Hz, 5 V, 0.1 ms in duration) at 1-minutes intervals for 10 minutes and submerged in 1 mL standard artificial cerebrospinal fluid (ACSF) (in mM: 125 mM NaCl, 5 mM KCl, 1.24 mM KH2PO4, 1.3 mM MgSO4, 2 mM CaCl2, 26 mM NaHCO3, and 10 mM glucose) oxygenated with 95% O2 and 5% CO2 at 36 °C in the presence and absence of tetrodotoxin (TTX) (0.5 μM). In a different set of experiments, electrical stimulation is applied to slices treated with Nefiracetam (1 μM) in the presence and absence of α-bungarotoxin (50 nM) or mecamylamine (3 μM). A 100 μL aliquot of the medium filtered with millipore filters (0.45 μM) is injected onto the cation-exchanger column of the autoanalyser to separate amino acids and the amount of glutamate released is calculated using known amino acid standard concentrations. |
| 體外活性 | 在DDY小鼠體內(nèi),Nefiracetam（>10 mg/kg）也會(huì)有效抑制Ro 5-4864誘導(dǎo)的抽搐.口服Nefiracetam可抑制EL小鼠體內(nèi)Ro 5-4864誘導(dǎo)的驚厥.在每次訓(xùn)練項(xiàng)目前,Nefiracetam給藥（1 time/day)有利于回避反應(yīng)的獲得過程. |
| 體內(nèi)活性 | Nefiracetam(0.01–0.1 μM)誘導(dǎo)Ach激發(fā)電流的短期抑制,Nefiracetam(1–10 μM)對(duì)電流具有長期增強(qiáng)作用。1 μM的Nefiracetam增加2倍鈣通道電流的長效組分,而不改變瞬變組分。Nefiracetam處理10分鐘后,Ach誘發(fā)的電流減少到對(duì)照組的30% (0.01 μM)和38%(0.1 μM)。Nefiracetam可與PKC通路發(fā)生相互作用提高煙堿Ach受體的活性,進(jìn)而增加從突出前末梢谷氨酸的釋放量,使海馬神經(jīng)傳遞的持久易化。認(rèn)知能力增強(qiáng)劑發(fā)揮作用的細(xì)胞機(jī)理可能是通過Nefiracetam與PKA和PKC通路的相互作用造成的。在大鼠海馬神經(jīng)元的原代培養(yǎng)中,Nefiracetam增加煙堿敏感的興奮性突觸后電流比率。在大鼠海馬切片的CA1區(qū)和齒狀回中,Nefiracetam誘導(dǎo)突觸傳導(dǎo)的持久易化, α-銀環(huán)蛇毒素和美加明可抑制該易化作用。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 70 mg/mL (284.21 mM), Sonication is recommended.
Ethanol : 24.6 mg/mL (100 mM)
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| 關(guān)鍵字 | Nefiracetam | DZL 221 | γ-Aminobutyric acid Receptor | GABA Receptor | DM 9384 | inhibit | Inhibitor | DZL221 | DM-9384 | Gamma-aminobutyric acid Receptor |
| 相關(guān)產(chǎn)品 | Penicillin G sodium salt | Valproic acid sodium salt | Valproic Acid | DL-Menthol | (-)-α-Pinene | Nikethamide | Riluzole | Chlorothymol | Halothane | Gabapentin |
| 相關(guān)庫 | 神經(jīng)保護(hù)化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 離子通道庫 | 膜蛋白靶向化合物庫 | 神經(jīng)退行性疾病化合物庫 | 藥物功能重定位化合物庫 | 疼痛相關(guān)化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |