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Chemical Compound Review

Translon     N-(2,6-dimethylphenyl)-2-(2- oxopyrrolidin...

Synonyms: Motiva, DMPPA, Nefiracetam, Nefiracetamum, DZL-221, ...
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Disease relevance of CCRIS 6729

  • The nefiracetam potentiating action was not affected by 24-h pretreatment of neurons with pertussis toxin, but was abolished by cholera toxin [1].
  • Persistent effects of delayed treatment with nefiracetam on the water maze task in rats with sustained cerebral ischemia [2].
  • In the thermal paw withdrawal test, p.o., s.c., i.t., and i.c.v. administration of nefiracetam dose dependently reversed the thermal hyperalgesia observed in nerve-injured mice [3].
  • Effects of the nootropic drug nefiracetam on the GABAA receptor-channel complex in dorsal root ganglion neurons [4].
  • Therefore, it is suggested that nefiracetam improves the dysfunction of cholinergic, GABAergic and/or monoaminergic neuronal function by acting at Ca2+ channel and enhancing the release of neurotransmitters, and modifies impairment of memory processes induced by drugs and hypoxia [5].

Psychiatry related information on CCRIS 6729

  • Nefiracetam (DM-9384) is a new pyrrolidone nootropic drug being developed for the treatment of Alzheimer's type and poststroke vascular-type dementia [1].
  • Physostigmine and nefiracetam were tested alone and in combination in 104 rabbits with a mean age of 28 months conditioned in the 750 ms delay eyeblink classical conditioning procedure [6].
  • Co-administration of nefiracetam with scopolamine was not necessary to achieve the antiamnesic action, as nefiracetam given during training significantly improved the memory deficits produced by scopolamine at the 6-h posttraining time [7].
  • The results obtained indicate that the protective action of DM-9384 against scopolamine-induced amnesia is due to its ability to reverse the ACh depletion [8].
  • 7. These results suggest that nefiracetam may be useful for the treatment of patients with Alzheimer's disease [9].

High impact information on CCRIS 6729


Chemical compound and disease context of CCRIS 6729


Biological context of CCRIS 6729


Anatomical context of CCRIS 6729

  • 5. Nefiracetam at a dose of 3 mg kg(-1) p.o. increased the activity of choline acetyltransferase in the hippocampus of A beta-(1-42)-infused rats [9].
  • Nefiracetam, a nootropic (cognition-enhancing) agent, facilitated neurotransmission in the dentate gyrus of rat hippocampal slices in a dose-dependent manner at concentrations ranged from 1 nM to 1 microM, being evident at 60-min washing-out of the drug [16].
  • In behavioral experiments in rats, nefiracetam (3 mg/kg) ameliorated amnesia induced by basal forebrain (BF) lesion or treatment of scopolamine [17].
  • To delineate its pathogenesis, we established the primary culture of uroepithelial cells of the canine urinary bladder, and then explored the effect of nefiracetam on the cultured cells [18].
  • In the Xenopus oocyte expression systems, nefiracetam potentiated currents through a variety of neuronal nicotinic ACh receptors (alpha 3beta 2, alpha 3beta 4, alpha 4 beta 2, alpha 4 beta 4, and alpha 7) to a different extent [16].

Associations of CCRIS 6729 with other chemical compounds

  • The effect of a new cognition enhancer, DM-9384, N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, on regional acetylcholine (ACh) levels and against scopolamine-induced ACh depletion was examined in mouse brain [8].
  • Finally, nefiracetam (p.o.)-induced analgesia in injured mice was not affected by opioid antagonist naloxone (s.c., i.t., and i.c.v.) but was dose dependently inhibited by nicotinic antagonist mecamylamine (i.t. and i.c.v.). The analgesic effect of i.t. nefiracetam was also blocked by i.t. mecamylamine pretreatment [3].
  • When added to the internal pipette solution, the protein kinase A inhibitor KT 5720 (0. 6 microM), but not the protein kinase C inhibitor calphostin C (0.5 microM), abolished the nefiracetam stimulation of the ACh receptor [19].
  • Nefiracetam, when administered orally t o EL mice, inhibited convulsions induced by the PBR agonist, Ro 5-4864, with an ED(50) of 17.2 mg/kg, whereas it did not inhibit the drug-induced convulsions in control DDY mice [20].
  • Ultrastructurally, nefiracetam exhibited reductions of intracellular interdigitation and infoldings of epithelial cells in the papillary ducts, whereas ibuprofen showed no changes in the identical portions [21].

Gene context of CCRIS 6729


Analytical, diagnostic and therapeutic context of CCRIS 6729


  1. Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons. Zhao, X., Kuryatov, A., Lindstrom, J.M., Yeh, J.Z., Narahashi, T. Mol. Pharmacol. (2001) [Pubmed]
  2. Persistent effects of delayed treatment with nefiracetam on the water maze task in rats with sustained cerebral ischemia. Takeo, S., Fukatsu, T., Miyake-Takagi, K., Takagi, N., Niimura, M., Nagakura, A., Ando, T., Tanonaka, K. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  3. Nonopioid and neuropathy-specific analgesic action of the nootropic drug nefiracetam in mice. Rashid, M.H., Ueda, H. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  4. Effects of the nootropic drug nefiracetam on the GABAA receptor-channel complex in dorsal root ganglion neurons. Huang, C.S., Ma, J.Y., Marszalec, W., Narahashi, T. Neuropharmacology (1996) [Pubmed]
  5. Effects of nefiracetam on amnesia animal models with neuronal dysfunctions. Hiramatsu, M., Shiotani, T., Kameyama, T., Nabeshima, T. Behav. Brain Res. (1997) [Pubmed]
  6. Nefiracetam and physostigmine: separate and combined effects on learning in older rabbits. Woodruff-Pak, D.S., Ewers, M., Shiotani, T., Watabe, S., Tanaka, M., Wenk, G.L. Neurobiol. Aging (2004) [Pubmed]
  7. Nefiracetam (DM-9384) preserves hippocampal neural cell adhesion molecule-mediated memory consolidation processes during scopolamine disruption of passive avoidance training in the rat. Doyle, E., Regan, C.M., Shiotani, T. J. Neurochem. (1993) [Pubmed]
  8. Reversal effect of DM-9384 on scopolamine-induced acetylcholine depletion in certain regions of the mouse brain. Abe, E. Psychopharmacology (Berl.) (1991) [Pubmed]
  9. Improvement by nefiracetam of beta-amyloid-(1-42)-induced learning and memory impairments in rats. Yamada, K., Tanaka, T., Mamiya, T., Shiotani, T., Kameyama, T., Nabeshima, T. Br. J. Pharmacol. (1999) [Pubmed]
  10. Piracetam and other structurally related nootropics. Gouliaev, A.H., Senning, A. Brain Res. Brain Res. Rev. (1994) [Pubmed]
  11. 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., Zhao, X., Marszalec, W., Yeh, J.Z., Fukunaga, K., Narahashi, T. Mol. Pharmacol. (2007) [Pubmed]
  12. Nefiracetam modulates acetylcholine receptor currents via two different signal transduction pathways. Nishizaki, T., Matsuoka, T., Nomura, T., Sumikawa, K., Shiotani, T., Watabe, S., Yoshii, M. Mol. Pharmacol. (1998) [Pubmed]
  13. Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and muscarinic receptors induced by cycloheximide. Nabeshima, T., Tohyama, K., Murase, K., Ishihara, S., Kameyama, T., Yamasaki, T., Hatanaka, S., Kojima, H., Sakurai, T., Takasu, Y. J. Pharmacol. Exp. Ther. (1991) [Pubmed]
  14. Nefiracetam prevents propofol-induced anterograde and retrograde amnesia in the rodent without compromising quality of anesthesia. O'Gorman, D.A., O'Connell, A.W., Murphy, K.J., Moriarty, D.C., Shiotani, T., Regan, C.M. Anesthesiology (1998) [Pubmed]
  15. The cognition-enhancer nefiracetam inhibits both necrosis and apoptosis in retinal ischemic models in vitro and in vivo. Ueda, M., Fujita, R., Koji, T., Ueda, H. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  16. Nefiracetam facilitates hippocampal neurotransmission by a mechanism independent of the piracetam and aniracetam action. Nomura, T., Nishizaki, T. Brain Res. (2000) [Pubmed]
  17. Cellular mechanisms underlying cognition-enhancing actions of nefiracetam (DM-9384). Yoshii, M., Watabe, S., Sakurai, T., Shiotani, T. Behav. Brain Res. (1997) [Pubmed]
  18. Effect of nefiracetam, a neurotransmission enhancer, on primary uroepithelial cells of the canine urinary bladder. Goto, K., Ishii, Y., Jindo, T., Furuhama, K. Toxicol. Sci. (2003) [Pubmed]
  19. Modulation of the neuronal nicotinic acetylcholine receptor-channel by the nootropic drug nefiracetam. Oyaizu, M., Narahashi, T. Brain Res. (1999) [Pubmed]
  20. Anticonvulsant actions of nefiracetam on epileptic EL mice and their relation to peripheral-type benzodiazepine receptors. Shiotani, T., Nakamoto, Y., Watabe, S., Yoshii, M., Nabeshima, T. Brain Res. (2000) [Pubmed]
  21. Early pathophysiological features in canine renal papillary necrosis induced by nefiracetam. Tsuchiya, Y., Yabe, K., Takada, S., Ishii, Y., Jindo, T., Furuhama, K., Suzuki, K.T. Toxicologic pathology. (2005) [Pubmed]
  22. Nefiracetam metabolism by human liver microsomes: role of cytochrome P450 3A4 and cytochrome P450 1A2 in 5-hydroxynefiracetam formation. Fujimaki, Y., Arai, N., Nakazawa, T., Fujimaki, M. J. Pharm. Pharmacol. (2001) [Pubmed]
  23. Effects of nefiracetam on the levels of brain-derived neurotrophic factor and synapsin I mRNA and protein in the hippocampus of microsphere-embolized rats. Ando, T., Takagi, N., Takagi, K., Kago, T., Takeo, S. Eur. J. Pharmacol. (2005) [Pubmed]
  24. Nefiracetam (DM-9384): effect on eyeblink classical conditioning in older rabbits. Woodruff-Pak, D.S., Li, Y.T. Psychopharmacology (Berl.) (1994) [Pubmed]
  25. A possible mechanism for improvement by a cognition-enhancer nefiracetam of spatial memory function and cAMP-mediated signal transduction system in sustained cerebral ischaemia in rats. Takeo, S., Niimura, M., Miyake-Takagi, K., Nagakura, A., Fukatsu, T., Ando, T., Takagi, N., Tanonaka, K., Hara, J. Br. J. Pharmacol. (2003) [Pubmed]
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