Neuroscience Research Compound · For laboratory research use only
Also known as DM-9384
Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide, development code DM-9384) is a pyrrolidone-type racetam developed by Daiichi Seiyaku. It is one of the more extensively studied racetams at the cellular level, with work on neuronal calcium channels, nicotinic acetylcholine receptors, NMDA receptors and protein kinase signalling1,2,3,4.
Published research includes patch-clamp studies in cell lines and cultured neurons, hippocampal slice electrophysiology, rodent learning models and toxicology studies1,2,3,4,5,6. A randomised clinical trial in post-stroke apathy has also been registered and published7.
As described in the research literature
As described in the research literature, nefiracetam increased a long-lasting component of calcium channel currents in NG108-15 cells; the enhanced currents were reduced by the L-type blocker nifedipine and were absent after pertussis toxin treatment, suggesting regulation through inhibitory G proteins1. In rat cortical neurons in long-term culture, it potentiated alpha4beta2-type nicotinic acetylcholine receptor currents and only weakly inhibited alpha7-type currents; the potentiation was abolished by cholera toxin, pointing to Gs proteins2.
Later studies examined glutamatergic signalling. In rat cortical and hippocampal neurons, potentiation of NMDA receptor currents depended on protein kinase C activation and was accompanied by reduced voltage-dependent magnesium block3. In the rat hippocampal CA1 region, enhancement of long-term potentiation was associated with CaMKII and PKC-alpha activation and with phosphorylation of AMPA and NMDA receptors; protein kinase A activity was unaffected4. Several of these effects followed a bell-shaped concentration-response relationship1,2,3,4.
What published studies have examined
Whole-cell patch-clamp recordings examined calcium channel currents in NG108-15 cells1 and nicotinic acetylcholine receptor subtypes in cultured rat cortical neurons, including the involvement of protein kinases and G proteins2.
NMDA receptor currents, magnesium block and PKC-alpha phosphorylation were examined in cultured rat neurons3. Field EPSPs and long-term potentiation in rat hippocampal slices were studied alongside immunoblotting for CaMKII, PKC and their substrates4.
Rats with continuous central exposure to amyloid-beta (1-42) were tested in Y-maze, water maze and passive avoidance tasks, with choline acetyltransferase activity and monoamine turnover measured in brain tissue5.
Sources [5]
Comparative studies in rats, dogs and monkeys reported renal papillary necrosis in dogs only, and investigated a species-specific role for a metabolite (M-18) and renal prostaglandin synthesis6. A parallel-group, randomised, placebo-controlled, double-blind two-centre trial in post-stroke apathy used change on the 14-item Apathy Scale at 12 weeks as its primary efficacy parameter7.
Enhancement of neuronal calcium channel currents by the nootropic agent, nefiracetam (DM-9384), in NG108-15 cells.
Yoshii M, Watabe S Brain Research, 1994.
Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons.
Zhao X, Kuryatov A, Lindstrom JM, et al. Molecular Pharmacology, 2001.
Nefiracetam potentiates N-methyl-D-aspartate (NMDA) receptor function via protein kinase C activation and reduces magnesium block of NMDA receptor.
Moriguchi S, Shioda N, Maejima H, et al. Molecular Pharmacology, 2007.
CaM kinase II and protein kinase C activations mediate enhancement of long-term potentiation by nefiracetam in the rat hippocampal CA1 region.
Moriguchi S, Shioda N, Han F, et al. Journal of Neurochemistry, 2008.
Improvement by nefiracetam of beta-amyloid-(1-42)-induced learning and memory impairments in rats.
Yamada K, Tanaka T, Mamiya T, et al. British Journal of Pharmacology, 1999.
Comprehensive evaluation of canine renal papillary necrosis induced by nefiracetam, a neurotransmission enhancer.
Tsuchiya Y, Takahashi Y, Jindo T, et al. European Journal of Pharmacology, 2003.
A Randomized, Placebo-Controlled, Double-Blind Efficacy Study of Nefiracetam to Treat Poststroke Apathy.
Starkstein SE, Brockman S, Hatch KK, et al. Journal of Stroke and Cerebrovascular Diseases, 2016.
PubMed 26915605 ↗DOI 10.1016/j.jstrokecerebrovasdis.2016.01.032 ↗
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.