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Chemical Compound Review

Draganon     1-(4-methoxyphenyl) carbonylpyrrolidin-2-one

Synonyms: Memodrin, Ampamet, Sarpul, aniracetam, Reset, ...
 
 
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Disease relevance of aniracetam

  • Effects of aniracetam on bladder overactivity in rats with cerebral infarction [1].
  • Delayed, post-injury treatment with aniracetam improves cognitive performance after traumatic brain injury in rats [2].
  • We investigated the ability of the antidementia agents, nicergoline, aniracetam and hydergine to stimulate PKC mediated alpha-secretase amyloid precursor protein (APP) processing in cultured human neuroblastoma SH-SY5Y cells [3].
  • The present study focused on the mechanism of cytoprotective effect of aniracetam on the primary rat astrocyte cultures exposed to simulated ischemia conditions in vitro [4].
  • Pretreatment with aniracetam (50 nmol i.c.v., 15 min before drugs) increases the ED50 values (mumol/kg i.p., 15 min) for GYKI 52466-induced protection against sound-induced clonic seizures in DBA/2 mice 7 fold, from 20.1 (11.9-33.9) to 142 (91.7-219), and for NBQX-induced protection 2 fold, from 39.7 (33.8-46.7) to 85.6 (63.9-115), respectively [5].
 

Psychiatry related information on aniracetam

  • Because the cholinergic system plays an important role in cognitive functions and Alzheimer's disease dementia, the present study was conducted to elucidate the mechanism of action of nefiracetam and aniracetam on neuronal nicotinic acetylcholine receptors (nnAChRs) [6].
  • Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents. A randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests [7].
  • Aniracetam failed to improve the picrotoxin-induced amnesia [8].
  • Impulsivity and AMPA receptors: aniracetam ameliorates impulsive behavior induced by a blockade of AMPA receptors in rats [9].
  • One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo [10].
 

High impact information on aniracetam

  • The nootropic agent aniracetam selectively and reversibly slows the desensitization kinetics of non-NMDA channels and lengthens their single-channel open times [11].
  • Simulations suggest that aniracetam either slows entry into a desensitized state or decreases the closing rate constant for ion channel gating [12].
  • We report here on the ability of IDRA 21 and aniracetam, two negative allosteric modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam-induced learning deficit in patas monkeys working in a complex behavioral task [13].
  • AMPA receptor GluRA subunits with mutations at position 750, a residue shown previously to control allosteric regulation by cyclothiazide, were analyzed for modulation of deactivation and desensitization by cyclothiazide, aniracetam, and thiocyanate [14].
  • Nefiracetam at 1 nM and aniracetam at 0.1 nM reversibly potentiated alpha 4 beta 2-type currents to 200 to 300% of control [6].
 

Chemical compound and disease context of aniracetam

 

Biological context of aniracetam

 

Anatomical context of aniracetam

 

Associations of aniracetam with other chemical compounds

 

Gene context of aniracetam

  • Exposure of cerebellar granule cells to AMPA (500 microM) + aniracetam (1 microM), a known blocker of AMPA receptor desensitization, evoked an accumulation of brain-derived neurotropic factor (BDNF) in the culture medium and enhanced TrkB-tyrosine phosphorylation following the release of BDNF [30].
  • In addition, aniracetam significantly stimulated of phospho-Erk1/2 kinase and phospho-Akt expression [4].
  • To study these mechanisms, the aniracetam-mediated modulation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-K)/Akt kinase pathways was determined [4].
  • In oocytes injected with GluR1 plus GluR2 RNAs, aniracetam more markedly potentiated current responses to AMPA and glutamate than those in oocytes injected with GluR1 RNA alone [31].
  • GYKI52466 and aniracetam treatments resulted in changes in both [(3)H]ifenprodil binding and NR2B mRNA levels, consistent with the association of this subunit and binding site in vitro [32].
 

Analytical, diagnostic and therapeutic context of aniracetam

  • We find that aniracetam enhances glutamate-evoked currents in whole-cell recordings and, in outside-out patches, strongly reduces glutamate receptor desensitization [33].
  • Oral administration of aniracetam (100 and 300 mg/kg) resulted in a significant and dose-dependent increase in bladder capacity in cerebral infarcted rats but had no effect on bladder capacity in sham-operated rats [1].
  • In order to examine if the nootropic drug, aniracetam, was capable of improving cognitive performance, 44 subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents were included in a randomized, double-blind, placebo-controlled, cross-over study [7].
  • Effects of aniracetam on extracellular levels of transmitter amino acids in the hippocampus of the conscious gerbils: an intracranial microdialysis study [34].
  • The results suggest that these effects might be due to a partial calcium agonist activity of aniracetam, and that the effects of aniracetam on amino acid levels might be a mechanism of protection against delayed neuronal death in the ischemic hippocampus, thereby improving memory dysfunction induced by ischemia/reperfusion [34].

References

  1. Effects of aniracetam on bladder overactivity in rats with cerebral infarction. Nakada, Y., Yokoyama, O., Komatsu, K., Kodama, K., Yotsuyanagi, S., Niikura, S., Nagasaka, Y., Namiki, M. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  2. Delayed, post-injury treatment with aniracetam improves cognitive performance after traumatic brain injury in rats. Baranova, A.I., Whiting, M.D., Hamm, R.J. J. Neurotrauma (2006) [Pubmed]
  3. Nicergoline stimulates protein kinase C mediated alpha-secretase processing of the amyloid precursor protein in cultured human neuroblastoma SH-SY5Y cells. Cedazo-Minguez, A., Bonecchi, L., Winblad, B., Post, C., Wong, E.H., Cowburn, R.F., Benatti, L. Neurochem. Int. (1999) [Pubmed]
  4. Erk1/2 and Akt kinases are involved in the protective effect of aniracetam in astrocytes subjected to simulated ischemia in vitro. Gabryel, B., Pudelko, A., Malecki, A. Eur. J. Pharmacol. (2004) [Pubmed]
  5. Aniracetam reverses the anticonvulsant action of NBQX and GYKI 52466 in DBA/2 mice. Chapman, A.G., al-Zubaidy, Z., Meldrum, B.S. Eur. J. Pharmacol. (1993) [Pubmed]
  6. 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]
  7. Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents. A randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests. Somnier, F.E., Ostergaard, M.S., Boysen, G., Bruhn, P., Mikkelsen, B.O. Psychopharmacology (Berl.) (1990) [Pubmed]
  8. Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions. Nabeshima, T., Noda, Y., Tohyama, K., Itoh, J., Kameyama, T. Eur. J. Pharmacol. (1990) [Pubmed]
  9. Impulsivity and AMPA receptors: aniracetam ameliorates impulsive behavior induced by a blockade of AMPA receptors in rats. Nakamura, K., Kurasawa, M., Shirane, M. Brain Res. (2000) [Pubmed]
  10. Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study. Senin, U., Abate, G., Fieschi, C., Gori, G., Guala, A., Marini, G., Villardita, C., Parnetti, L. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (1991) [Pubmed]
  11. Modulation of the time course of fast EPSCs and glutamate channel kinetics by aniracetam. Tang, C.M., Shi, Q.Y., Katchman, A., Lynch, G. Science (1991) [Pubmed]
  12. Modulation of excitatory synaptic transmission by drugs that reduce desensitization at AMPA/kainate receptors. Vyklicky, L., Patneau, D.K., Mayer, M.L. Neuron (1991) [Pubmed]
  13. 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys. Thompson, D.M., Guidotti, A., DiBella, M., Costa, E. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  14. AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate. Partin, K.M., Fleck, M.W., Mayer, M.L. J. Neurosci. (1996) [Pubmed]
  15. N-methyl-D-aspartate neurotoxicity in hippocampal slices: protection by aniracetam. Pizzi, M., Consolandi, O., Memo, M., Spano, P. Eur. J. Pharmacol. (1995) [Pubmed]
  16. Nootropic drugs and brain cholinergic mechanisms. Pepeu, G., Spignoli, G. Prog. Neuropsychopharmacol. Biol. Psychiatry (1989) [Pubmed]
  17. Effects of D-cycloserine and aniracetam on spatial learning in rats with entorhinal cortex lesions. Zajaczkowski, W., Danysz, W. Pharmacol. Biochem. Behav. (1997) [Pubmed]
  18. WEB 1881 FU ameliorates impairment of working memory induced by scopolamine and cerebral ischemia in the three-panel runway task. Ohno, M., Yamamoto, T., Kitajima, I., Ueki, S. Jpn. J. Pharmacol. (1990) [Pubmed]
  19. Treatment of insomnia by concomitant therapy with Zopiclone and Aniracetam in patients with cerebral infarction, cerebroatrophy, Alzheimer's disease and Parkinson's disease. Katsunuma, H., Shimizu, T., Ogawa, K., Kubo, H., Ishida, H., Yoshihama, A. Psychiatry and clinical neurosciences. (1998) [Pubmed]
  20. Selective effects of aniracetam across receptor types and forms of synaptic facilitation in hippocampus. Xiao, P., Staubli, U., Kessler, M., Lynch, G. Hippocampus. (1991) [Pubmed]
  21. Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam. Ito, I., Tanabe, S., Kohda, A., Sugiyama, H. J. Physiol. (Lond.) (1990) [Pubmed]
  22. Facilitation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor transmission in the suprachiasmatic nucleus by aniracetam enhances photic responses of the biological clock in rodents. Moriya, T., Ikeda, M., Teshima, K., Hara, R., Kuriyama, K., Yoshioka, T., Allen, C.N., Shibata, S. J. Neurochem. (2003) [Pubmed]
  23. Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures. Copani, A., Genazzani, A.A., Aleppo, G., Casabona, G., Canonico, P.L., Scapagnini, U., Nicoletti, F. J. Neurochem. (1992) [Pubmed]
  24. Receptor changes and LTP: an analysis using aniracetam, a drug that reversibly modifies glutamate (AMPA) receptors. Staubli, U., Ambros-Ingerson, J., Lynch, G. Hippocampus. (1992) [Pubmed]
  25. Antidepressant-like effects of aniracetam in aged rats and its mode of action. Nakamura, K., Tanaka, Y. Psychopharmacology (Berl.) (2001) [Pubmed]
  26. Group II metabotropic glutamate receptors are a common target of N-anisoyl-GABA and 1S,3R-ACPD in enhancing ACh release in the prefrontal cortex of freely moving SHRSP. Shirane, M., Nakamura, K. Neuropharmacology (2000) [Pubmed]
  27. The "kynurenate test", a biochemical assay for putative cognition enhancers. Pittaluga, A., Vaccari, D., Raiteri, M. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  28. Enhancement of contextual fear-conditioning by putative (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators and N-methyl-D-aspartate (NMDA) receptor antagonists in DBA/2J mice. Lu, Y., Wehner, J.M. Brain Res. (1997) [Pubmed]
  29. Site-specific activation of dopamine and serotonin transmission by aniracetam in the mesocorticolimbic pathway of rats. Nakamura, K., Shirane, M., Koshikawa, N. Brain Res. (2001) [Pubmed]
  30. AMPA protects cultured neurons against glutamate excitotoxicity through a phosphatidylinositol 3-kinase-dependent activation in extracellular signal-regulated kinase to upregulate BDNF gene expression. Wu, X., Zhu, D., Jiang, X., Okagaki, P., Mearow, K., Zhu, G., McCall, S., Banaudha, K., Lipsky, R.H., Marini, A.M. J. Neurochem. (2004) [Pubmed]
  31. Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam. Tsuzuki, K., Takeuchi, T., Ozawa, S. Brain Res. Mol. Brain Res. (1992) [Pubmed]
  32. Ionotropic glutamate receptor modulation preferentially affects NMDA receptor expression in rat hippocampus. Healy, D.J., Meador-Woodruff, J.H. Synapse (2000) [Pubmed]
  33. Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus. Isaacson, J.S., Nicoll, R.A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  34. Effects of aniracetam on extracellular levels of transmitter amino acids in the hippocampus of the conscious gerbils: an intracranial microdialysis study. Yu, S., Cai, J. Neurosci. Lett. (2003) [Pubmed]
 
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