Nefiracetam Research Articles

In silicoandin vivostudy of radio-iodinated nefiracetam as a radiotracer for brain imaging in mice

AbstractThis study presents development and characterization of a radiotracer, [125I]iodonefiracetam ([125I]iodoNEF). Labeling with high yield and radiochemical purity was achieved through the formation of a [125I]iodoNEF radiotracer after investigating many factors like oxidizing agent content (chloramines-T (Ch-T)), substrate amount (Nefiracetam (NEF)), pH of reaction mixture, reaction time and temperature. Nefiracetam (NEF) is known as nootropic agent, acting asN-methyl-d-aspartic acid receptor ligand (NMDA). The radiolabeled compound was stable, and exhibited the logarithm of the partition coefficient (logp) value of [125I]iodonefiracetam as 1.85 (lipophilic). Biodistribution studies in normal mice confirmed the suitability of the [125I]iodoNEF radiotracer as a novel tracer for brain imaging. High uptake of 8.61 ± 0.14 percent injected dose/g organ was observed in mice

ESLICARBAZEPINE AND MEMORY IMPAIRMENT IN TEMPORAL LOBE EPILEPSY: A STUDY ON THE ATTENUATING EFFECT OF NEFIRACETAM

Objectives: The objectives of the present investigation were to evaluate the memory impairment (MI) activity of eslicarbazepine (ESL) in temporal lobe epilepsy (TLE) at a normal and reduced dose, to evaluate the possible protective effect of nefiracetam (NEF) on MI induced by ESL at a normal and reduced dose, and to evaluate the antiepileptic activity of ESL on TLE in the presence and absence of NEF.
 Methods: MI activity was evaluated by Barnes maze (BM) on lithium-pilocarpine-induced TLE in Wistar albino rats. Rats were trained by releasing from the portable start-up box after keeping sometimes inside, to find the fixed dark escape hole of BM. Mild aversive light overhead was used to motivate the finding. Animals failed to do so were guided manually. Trained animals were taken for the study and checked the escape latency time (ELT) and the error scores (error entry). The treatment was given for 1 month and MI activity was measured on every 7th day and antiepileptic activity on every 8th day. Phenytoin was used as standard antiepileptic drug (AED) to compare the MI extent of ESL.
 Results: ESL-treated group animals had shown increased ELT and error scores, on comparison with control group, implying the MI as a result treatment of the AED ESL. MI was dose dependent and shown decreased MI in animals treated with half dose of ESL. When NEF was administered with the ESL significantly decreased the MI as well as showed potent anticonvulsant activity when compared to control and ESL alone treated group. The levels of acetylcholinesterase (AChE) in ESL group were observed to be increased against control group. Cotreatment of NEF results in decreased levels of AChE on comparison with control and the group treated with ESL.
 Conclusion: The reduced dose of ESL and NEF combination was found to have synergized the protecting effect against MI compared to normal ESL and NEF group without altering anticonvulsant activity. However, further studies are required to elicit detailed protective activity of NEF on MI induced by ESL.

Nefiracetam Attenuates Pro-Inflammatory Cytokines and GABA Transporter in Specific Brain Regions of Rats with Post-Ischemic Seizures

Background/Aims: Prior studies demonstrated that pro-inflammatory cytokines (PICs) including IL-1β, IL-6 and TNF-α contribute to regulation of epilepsy-associated pathophysiological processes in the specific brain regions, namely the parietal cortex, hippocampus and amygdala. Moreover, GABA transporter type 1 and 3 (GAT-1 and GAT-3) modulating extracellular GABA levels are engaged in the role played by PICs in epileptogenesis. Note that brain ischemic injury also elevates cerebral PICs. Thus, in this report we examined the effects of nefiracetam (NEF), a pyrrolidone derivative, on the levels of IL-1β, IL-6 and TNF-α, and expression of GAT-1 and GAT-3 in the parietal cortex, hippocampus and amygdala using a rat model of post-ischemic nonconvulsive seizure (NCS). Methods: NCS was evoked by the middle cerebral artery occlusion (MCAO). ELISA and Western Blot analysis were employed to determine the levels of PICs and GAT-1/GAT-3, respectively. Results: MCAO significantly increased IL-1β, IL-6 and TNF-α in the parietal cortex, hippocampus and amygdala as compared with sham control animals (P<0.05 vs. control rats). Also, in these specific brain regions expression of GAT-1 and GAT-3 was amplified; and the levels of GABA were decreased in rats following MCAO (P<0.05 vs. control rats). Systemic administration of NEF significantly attenuated the elevated PICs, amplified GAT-1 and GAT-3 as well as impaired GABA. NEF also attenuated the number of NCS events following MCAO. Conclusion: our data demonstrate that NEF improves post-ischemia evoked-NCS by altering PICs, GABA transporters thereby alleviating GABA in the parietal cortex, hippocampus and amygdala. This support a role for PICs and GABA in engagement of the adaptive responses associated with epileptic activity, but also suggests that NEF has anti-epileptic effects via PICs-GABA mechanisms, having pharmacological implications to target the specific PICs for neuronal dysfunction and vulnerability related to post-ischemic seizures and cognitive impairment.

Nefiracetam attenuates post-ischemic nonconvulsive seizures in rats and protects neuronal cell death induced by veratridine and glutamate

AimsStroke patients are at a high risk of developing post-ischemic seizures and cognitive impairment. Nefiracetam (NEF), a pyrrolidone derivative, has been shown to possess both anti-epileptic and cognitive-enhancing properties. In this study the anti-seizure effects of NEF were evaluated in a rat model of post-ischemic nonconvulsive seizures (NCSs). Its potential mechanisms were investigated in neuronal cell culture assays of neurotoxicity associated with ischemic brain injury and epileptogenesis. Main methodsIn the in vivo study, rats received 24h permanent middle cerebral artery occlusion. NEF was administered intravenously either at 15min post-injury but prior to the first NCS event (30mg/kg, pre-NCS treatment) or immediately after the first NCS occurred (30 or 60mg/kg, post-NCS treatment). In the in vitro study, neuronal cell cultures were exposed to veratridine or glutamate and treated with NEF (1–500nM). Key findingsThe NEF pre-NCS treatment significantly reduced the NCS frequency and duration, whereas the higher NEF dose (60mg/kg) was required to achieve similar effects when given after NCS occurred. The NEF treatment also dose-dependently (5–500nM) protected against neuronal cell death induced by veratridine as measured by MTT cell viability assay, but higher doses (250–500nM) were required against glutamate toxicity. SignificanceThe anti-seizure property of NEF was demonstrated in a clinically relevant rat model of post-ischemic NCS. The preferential effects of NEF against in vitro veratridine toxicity suggest the involvement of its modulation of sodium channel malfunction. Future studies are warranted to study the mechanisms of NEF against ischemic brain injury and post-ischemic seizures.

Effects of Nefiracetam, a Novel Pyrrolidone‐type Nootropic Agent, on the Amygdala‐kindled Seizures in Rats

Nefiracetam (NEF) is a novel pyrrolidonetype nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the effects of NEF in amygdala-kindled seizures and its potential for antiepileptic therapy. Effects of NEF on fully amygdala-kindled seizures and development of amygdala-kindled seizures were investigated in rats and compared with those of levetiracetam (LEV), a pyrrolidone-type antiepileptic drug (AED). In fully amygdala-kindled rats, NEF (25, 50, and 100 mg/kg, p.o.) decreased afterdischarge induction, afterdischarge duration, seizure stage, and motor seizure duration in a dose-dependent manner. LEV (25, 50, and 100 mg/kg, p.o.) had no effects on afterdischarge induction and slightly decreased afterdischarge duration, whereas it markedly decreased seizure stage and motor seizure duration. In contrast to the results in fully amygdala-kindled rats, NEF (25 and 50 mg/kg/day, p.o.) had few or no effects on the development of amygdala-kindled seizures. As well as fully amygdala-kindled seizures, LEV (50 mg/kg/day, p.o.) markedly inhibited the development of behavioral seizures without reducing daily afterdischarge duration. Although NEF possesses potent anticonvulsant effects on fully amygdala-kindled seizures, it has few or no effects on the development of amygdala-kindled seizures. LEV shows marked anticonvulsant effects on both phases of kindling. In fully amygdala-kindled rats, NEF inhibits both electroencephalographic and behavioral seizures, whereas LEV inhibits only behavioral seizures. This double dissociation suggests that NEF has a distinct anticonvulsant spectrum and mechanisms from those of LEV.

Anticonvulsant Properties of the Novel Nootropic Agent Nefiracetam in Seizure Models of Mice and Rats

Nefiracetam (NEF) is a novel pyrrolidone-type nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the anticonvulsant effect of NEF and its potential for antiepileptic therapy. The anticonvulsant properties of NEF were investigated in experimental seizure models of mice and rats, compared with levetiracetam (LEV) and other standard antiepileptic drugs [AEDs; zonisamide (ZNS), phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA), diazepam (DZP), and ethosuximide (ESM)]. With reference to standard programs for evaluating potential AEDs, the study included the traditional maximal electroshock seizure and subcutaneous chemoconvulsant (pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate) seizure tests and two threshold models (the increasing-current electroshock seizure test and intravenous pentylenetetrazole seizure threshold test). Neurotoxic activities were examined with the rotarod test and traction test. NEF inhibited electroshock-induced seizures at nontoxic doses, whereas it had no effect on seizures chemically induced by pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate. The anticonvulsant spectrum of NEF paralleled that of ZNS, PHT, and CBZ. The anticonvulsant efficacy of NEF was comparable with that of ZNS and less potent than that of PHT, CBZ, and DZP. However, the safety margin of NEF was superior to that of ZNS, CBZ, VPA, and DZP. LEV showed only slight anticonvulsant effects in threshold models, and it was not effective in conventional screening models. These results suggest that NEF has distinct anticonvulsant spectrum and mechanisms from those of LEV. NEF is an orally active and safe AED, and it possesses a potential for antiepileptic therapy.

Nefiracetam (DM‐9384): A Novel Antiamnesic Drug

Nefiracetam (DM‐9384): A Novel Antiamnesic Drug

Nefiracetam shows some promise

Nefiracetam shows some promise

Simultaneous determination of nefiracetam and its metabolites by high-performance liquid chromatography

A reversed-phase high-performance liquid chromatographic assay was developed to simultaneously quantitate nefiracetam (NEF), a novel nootropic agent, and its three known oxidized metabolites (N-[(2,6-dimethylphenylcarbamoyl)methyl]succinamic acid (5-COOH-NEF), 4-hydroxy-NEF and 5-hydroxy-NEF) in human serum and urine. The quantitative procedure was based on solid-phase extraction with Sep-Pak C 18 and ultraviolet detection at 210 nm. The calibration curves of NEF and the metabolites were linear over a wide range of concentrations (0.5–21.5 nmol/ml for NEF and 0.4–9.5 nmol/ml for metabolites in serum and 4–86 nmol/ml for NEF and 8–190 nmol/ml for metabolites in urine). Intra- and inter-day assay coefficients of variation for the compounds were less than 10%. The limit of detection was 0.1 nmol/ml for NEF, 5-COOH-NEF and 4-hydroxy-NEF, and 0.2 nmol/ml for 5-hydroxy-NEF in both serum and urine. This method is applicable for the determination of NEF and its metabolites in human serum and urine with satisfactory accuracy and precision.