Substance
ID:73649
Names and Identifiers
IUPAC name
N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide
Synonyms
DM 9384DZL-221NefiracetamTranslon
IUPAC Traditional name
nefiracetam
Registration numbers
CAS Number
Properties
Safety Information
Storage Condition
-20°C
Product Information
Salt Data
Free Base
Molecule Details
Research Area
Description
Neurological Disease
Biological Activity
Description
Nefiracetam (Translon) is a GABAergic, cholinergic, and monoaminergic neuronal systems enhancer for Ro 5-4864-induced convulsions.
Targets
IC50
In Vitro
Nefiracetam at a concentration of 1 μM increases a long-lasting component of calcium channel currents two-fold without affecting a transient component. [2] Nefiracetam induces a short-term depression of ACh-evoked currents at submicromolar concentrations (0.01–0.1 μM) and a long-term enhancement of the currents at micromolar concentrations (1–10 μM). Nefiracetam interacts with PKA and PKC pathways, which may explain a cellular mechanism for the action of cognition-enhancing agents. Lower (submicromolar) concentrations of the nootropic Nefiracetam reduces ACh-evoked currents to 30% (0.01 μM) and 38% (0.1 μM) of control after a 10-minute treatment [3] In primary cultures of rat hippocampal neurons, nefiracetam increases the rate of nicotine-sensitive miniature excitatory postsynaptic currents. Nefiracetam induces a long-lasting facilitation of synaptic transmission in both the CA1 area and the dentate gyrus of rat hippocampal slices, and the facilitation is inhibited by α-bungarotoxin and mecamylamine. Nefiracetam enhances activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to a sustained facilitation of hippocampal neurotransmission. [4]
In Vivo
Nefiracetam administered orally inhibits Ro 5-4864-induced convulsions in EL mice. Nefiracetam also efficiently inhibits Ro 5-4864-induced convulsions in DDY mice at doses higher than 10 mg/kg. [1] Nefiracetam administered daily 1 hour before each training session facilitates the acquisition process of the avoidance response. [5]
Clinical Trials
Features
Protocol
Kinase Assay [4]
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.
Cell Assay [3]
Cell Lines
Oocytes
Concentrations
~1 μM
Incubation Time
24 hours - 48 hours
Methods
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.
Animal Study [1]
Animal Models
Adult male EL mice weighing 25–30 g and adult male DDY mice
Formulation
Doses
10 mg/kg
Administration
Administered via i.v. or p.o.
Molecular Spectra
No Data Available
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References
• Nishizaki T, et al. Mol Pharmacol, 1998, 53(1), 1-5.
• Yoshii M, et al. Brain Res, 1994, 642(1-2), 123-131.
• Nishizaki T, et al. Brain Res Mol Brain Res, 2000, 80(1), 53-62.
• Sakurai T, et al. Jpn J Pharmacol, 1989, 50(1), 47-53.
• Shiotani T, et al. Brain Res, 2000, 859(2), 255-261.