Nefiracetam 是一种 GABA 能、胆碱能和单胺能神经元系统增强剂，用于治疗 Ro 5-4864 引起的抽搐。

Nefiracetam are underway in Phase 2 trials. Nefiracetam, a GABAergic、 cholinergic、and monoaminergic neuronal system enhancer, is used for Ro 5-4864-induced convulsions.

在DDY小鼠体内,Nefiracetam（>10 mg/kg）也会有效抑制Ro 5-4864诱导的抽搐.口服Nefiracetam可抑制EL小鼠体内Ro 5-4864诱导的惊厥.在每次训练项目前,Nefiracetam给药（1 time/day)有利于回避反应的获得过程.

Nefiracetam(0.01–0.1 μM)诱导Ach激发电流的短期抑制,Nefiracetam(1–10 μM)对电流具有长期增强作用。1 μM的Nefiracetam增加2倍钙通道电流的长效组分,而不改变瞬变组分。Nefiracetam处理10分钟后,Ach诱发的电流减少到对照组的30% (0.01 μM)和38%(0.1 μM)。Nefiracetam可与PKC通路发生相互作用提高烟碱Ach受体的活性,进而增加从突出前末梢谷氨酸的释放量,使海马神经传递的持久易化。认知能力增强剂发挥作用的细胞机理可能是通过Nefiracetam与PKA和PKC通路的相互作用造成的。在大鼠海马神经元的原代培养中,Nefiracetam增加烟碱敏感的兴奋性突触后电流比率。在大鼠海马切片的CA1区和齿状回中,Nefiracetam诱导突触传导的持久易化, α-银环蛇毒素和美加明可抑制该易化作用。

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.

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)

77191-36-7

C14H18N2O2

246.31

奈非西坦;DM9384;DZL-221;Nefiracetam

DMSO:24.6 mg/mL (100 mM)
Ethanol:24.6 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years