CAS 77191-36-7|N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide|nefiracetam|DZL-221|Nefiracetam|Translon|DM 9384|DM-9384|(2-(2-oxopyrrolidin-1-yl)-N-(2,6-dimethylphenyl)-acetamide)|Nefiracet...

C₁₄H₁₈N₂O₂

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)

NGHTXZCKLWZPGK-UHFFFAOYSA-N

O=C(Nc1c(C)cccc1C)CN1CCCC1=O

C(N1C(=O)CCC1)C(=O)Nc1c(cccc1C)C

Acid pKa

13.745938

H Acceptors

H Donor

LogD (pH = 5.5)

1.5831947

LogD (pH = 7.4)

1.5831946

Log P

1.5831947

Molar Refractivity

71.5989

Polarizability

26.586145

Polar Surface Area

49.41

Rotatable Bonds

Lipinski's Rule of Five

true

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

TranslonNefiracetamDZL-221DM 9384NefiracetamDM-9384(2-(2-oxopyrrolidin-1-yl)-N-(2,6-dimethylphenyl)-acetamide)

IUPAC Traditional name

Salt Data

Free Base

Empirical Formula (Hill Notation)

C14H18N2O2

Apperance

white to off-white solid

Solubility

DMSO: >5 mg/mL

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• 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.

• Nishizaki T, et al. Mol Pharmacol, 1998, 53(1), 1-5.

• Yoshii M, et al. Brain Res, 1994, 642(1-2), 123-131.

Data Source

Commercial Catalog

Academic Data

Names and Identifiers

IUPAC name

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

Synonyms

TranslonNefiracetamDZL-221DM 9384NefiracetamDM-9384(2-(2-oxopyrrolidin-1-yl)-N-(2,6-dimethylphenyl)-acetamide)

IUPAC Traditional name

nefiracetam

Registration numbers

PubChem SID

PubChem CID

CAS Number

MDL Number

References

PubChem Literature

From Data Sources

• 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.

• Nishizaki T, et al. Mol Pharmacol, 1998, 53(1), 1-5.

• Yoshii M, et al. Brain Res, 1994, 642(1-2), 123-131.

Bioactivity

PubChem BioAssay

Molecule 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.

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.