N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide

• ChemBase ID: 72828
• Molecular Formular: C14H18N2O2
• Molecular Mass: 246.30492
• Monoisotopic Mass: 246.13682783
• SMILES: C(N1C(=O)CCC1)C(=O)Nc1c(cccc1C)C
• Canonical SMILES: O=C(Nc1c(C)cccc1C)CN1CCCC1=O
• InChI: InChI=1S/C14H18N2O2/c1-10-5-3-6-11(2)14(10)15-12(17)9-16-8-4-7-13(16)18/h3,5-6H,4,7-9H2,1-2H3,(H,15,17)
• InChIKey: NGHTXZCKLWZPGK-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide
• IUPAC Traditional name: nefiracetam
• Synonyms: DM 9384; Translon; DZL-221; Nefiracetam; (2-(2-oxopyrrolidin-1-yl)-N-(2,6-dimethylphenyl)-acetamide); DM-9384; Nefiracetam

Database IDs

• CAS Number: 77191-36-7
• MDL Number: MFCD00209882
• PubChem SID: 162037749
• PubChem CID: 71157

CALCULATED PROPERTIES

• Acid pKa: 13.745938
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 1.5831947
• LogD (pH = 7.4): 1.5831946
• Log P: 1.5831947
• Molar Refractivity: 71.5989 cm^3
• Polarizability: 26.586145 Å^3
• Polar Surface Area: 49.41 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO: >5 mg/mL
• Apperance: white to off-white solid

Safety Information

• Storage Condition: -20°C
• RTECS: UX9655650
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H319
• GHS Precautionary statements: P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves

Product Information

• Salt Data: Free Base
• Empirical Formula (Hill Notation): C14H18N2O2

DETAILS

Selleck Chemicals - S1969

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.
• 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]

Protocol

• 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.
• Protocol: 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). Ca^2+ -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.
• Protocol: Animal Study ^[1]
• Animal Models: Adult male EL mice weighing 25–30 g and adult male DDY mice
• Doses: 10 mg/kg
• Administration: Administered via i.v. or p.o.

References

• References: [1] Shiotani T, et al. Brain Res, 2000, 859(2), 255-261.
• References: [2] Yoshii M, et al. Brain Res, 1994, 642(1-2), 123-131.
• References: [3] Nishizaki T, et al. Mol Pharmacol, 1998, 53(1), 1-5.
• References: [4] Nishizaki T, et al. Brain Res Mol Brain Res, 2000, 80(1), 53-62.
• References: [5] Sakurai T, et al. Jpn J Pharmacol, 1989, 50(1), 47-53.

Sigma Aldrich - N2288

Biochem/physiol Actions
Nefiracetam (NEF) is a pyrrolidonetype nootropic agent with various pharmacologic as well as cognition enhancing effects. In amygdala-kindled seizures, nefiracetam inhibits both electroencephalographic and behavioral seizures. NEF has a distinct anticonvulsant spectrum.

REFERENCES

• Shiotani T, et al. Brain Res, 2000, 859(2), 255-261.
• Yoshii M, et al. Brain Res, 1994, 642(1-2), 123-131.
• Nishizaki T, et al. Mol Pharmacol, 1998, 53(1), 1-5.
• 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.