Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine‐binding site of N‐methyl‐D‐aspartate receptor

  title={Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine‐binding site of N‐methyl‐D‐aspartate receptor},
  author={Shigeki Moriguchi and Tomoya Tanaka and Toshio Narahashi and Kohji Fukunaga},
Sunifiram is a novel pyrrolidone nootropic drug structurally related to piracetam, which was developed for neurodegenerative disorder like Alzheimer's disease. Sunifiram is known to enhance cognitive function in some behavioral experiments such as Morris water maze task. To address question whether sunifiram affects N‐methyl‐D‐aspartate receptor (NMDAR)‐dependent synaptic function in the hippocampal CA1 region, we assessed the effects of sunifiram on NMDAR‐dependent long‐term potentiation (LTP… 
CaMKII activity is essential for improvement of memory‐related behaviors by chronic rivastigmine treatment
The stimulation of CaMKII activity in the hippocampus is essential for rivastigmine‐induced memory improvement in OBX mice and long‐term potentiation in the hippocampal CA1 region was markedly restored by rivASTigmine treatments.
Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening
Findings presented here showcase highly potential cholinergic agents, with expected partial agonist activity towards glycine binding pocket of NMDAR which could lead to development and optimisation of novel nootropic drugs.
Synthesis and discovery of the putative cognitive enhancer BRS-015 : effect on glutamatergic transmission and synaptic plasticity
BRS-015 has striking enhancing properties on AMPA receptor mediated synaptic transmission at mossy fibre synapses either by directly interacting with AMPA receptors or via indirect modulation, the mechanisms of which could lead to synapse strengthening.
Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic
This review is concentrated on the main pathways, namely, dopaminergic and cholinergic system, and the involvement of amyloid precursor protein and secondary messenger in improving the cognitive performance.
Pharmacogenomics of Alzheimer's disease: novel therapeutic strategies for drug development.
Future perspectives for the global management of AD predict that genomics and proteomics may help in the search for reliable biomarkers, and the implementation of pharmacogenomic strategies will contribute to optimize drug development and therapeutics in AD and related disorders.
Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings
  • F. Gualtieri
  • Physics
    Journal of enzyme inhibition and medicinal chemistry
  • 2016
This paper is a review of the work of the former academic group of research that identified two very potent molecules: Unifiram and Sun ifiram that for a variety of reasons were not protected by a patent.


CaM kinase II and protein kinase C activations mediate enhancement of long‐term potentiation by nefiracetam in the rat hippocampal CA1 region
The results suggest that nefiracetam potentiates AMPA receptor‐mediated fEPSPs through CaMKII activation and enhances NMDA receptor‐dependent LTP through potentiation of the post‐synaptic CaMK II and protein kinase C activities likely contribute to improvement of cognitive function.
Nefiracetam Potentiates N-Methyl-d-aspartate (NMDA) Receptor Function via Protein Kinase C Activation and Reduces Magnesium Block of NMDA Receptor
It was concluded that nefiracetam potentiated NMDA currents not by acting as a partial agonist but by interacting with PKC, allosterically enhancing glycine binding, and attenuating voltage-dependent Mg2+ block.
Potentiation of N-Methyl-d-aspartate-Induced Currents by the Nootropic Drug Nefiracetam in Rat Cortical Neurons
It was concluded that nefiracetam potentiated NMDA currents through interactions with the glycine binding site of the NMDA receptor.
Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.
Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices and the amplitudes of the potentiation were not changed by the formation of long‐term potentiation.
Protein kinase C‐mediated enhancement of NMDA currents by metabotropic glutamate receptors in Xenopus oocytes.
A role for metabotropic glutamate receptors in modulation of NMDA‐mediated processes is suggested in Xenopus oocytes injected with rat brain RNA and under conditions that eliminate the oocyte's endogenous calcium‐dependent chloride current.
Ca2+/calmodulin‐dependent protein kinase II‐dependent long‐term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin
It is suggested that CaM kinase II plays critical roles in LTP induction in the SCN and that melatonin has inhibitory effects on synaptic plasticity through CaM Kinase II.
Nefiracetam activation of CaM kinase II and protein kinase C mediated by NMDA and metabotropic glutamate receptors in olfactory bulbectomized mice
Nefiracetam ameliorates OBX‐induced deficits in memory‐related behaviors and impairment of LTP in the hippocampal CA1 region through activation of NMDAR and mGluR5, thereby leading to an increase in activities of CaMKIIα (Thr286) and PKCα (Ser657), respectively.
Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons.
Nefiracetam potentiating action was not affected by 24-h pretreatment of neurons with pertussis toxin, but was abolished by cholera toxin, indicating that nnAChRs are an important site of action of nefiracetAM and G(s) proteins may be its crucial target.
Dementia of the Alzheimer's Type: Changes in Hippocampal L‐[3H]Glutamate Binding
The results suggest that glutamatergic neurotransmission within the hippocampal formation is likely to be severely impaired in Alzheimer's disease, which may account for some of the cognitive decline and memory deficits that characterize DAT.
Regulation of N-methyl-D-aspartate receptor function by constitutively active protein kinase C.
Application of PKM to inside-out patches taken from cultured neurons increased the probability of channel opening without changing single-channel current amplitudes or channel open times, indicating the activation of protein kinase C is associated with potentiation of NMDA receptor function in hippocampal neurons largely through an increase in the probabilityof channel opening.