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CNS Drugs

, Volume 6, Issue 4, pp 331–337 | Cite as

Nefiracetam

  • Karen L. Goa
  • Paul Benfield
New Drug Profile

Summary

• Nefiracetam (DM 9384) is a pyrrolidone derivative with potential for use in patients with dementia secondary to cerebrovascular disorders or Alzheimer’s disease.

• It is thought to act by normalising dysfunctional acetylcholine, γ-aminobutyric acid (GABA) and possibly monoamine neurotransmitter systems, but it may also facilitate NIL-type calcium channel opening.

• Nefiracetam for 2 to 12 months improved cognitive function and psychiatric symptoms in patients with dementia due to cerebrovascular disorders.

• Nefiracetam was at least as effective as idebenone and was superior to placebo in patients with cerebrovascular dementia in large double-blind 8-week trials.

• Adverse events as reported in clinical trials are infrequent and are mainly gastrointestinal in nature.

Keywords

Dementia Adis International Limited Idebenone Cerebrovascular Disorder Aniracetam 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Watabe S, Yamaguchi H, Ashida S-I. DM-9384, a new cognition enhancing agent, increases the turnover of components of the GABAergic system in the rat cerebral cortex. Eur J Pharmacol 1993; 238: 303–9PubMedCrossRefGoogle Scholar
  2. 2.
    Tanaka S, Watabe S, Kakihata K, et al. Effects of the new cognition-enhancing agent nefiracetam in rats with cerebral embolism. Arzneimittel Forschung 1992; 42: 1274–8PubMedGoogle Scholar
  3. 3.
    Nabeshima T, Noda Y, Tohyama K, et al. Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions. Eur J Pharmacol 1990; 178: 143–9PubMedCrossRefGoogle Scholar
  4. 4.
    Hiramatsu M, Koide T, Ishihara S-i, et al. Involvement of the cholinergic system in the effects of nefiracetam (DM-9384) on carbon monoxide (CO)-induced acute and delayed amnesia. Eur J Pharmacol 1992; 216: 279–85PubMedCrossRefGoogle Scholar
  5. 5.
    Kawajiri S, Taniguchi K, Sakurai T, et al. Nefiracetam enhances acetylcholine outflow from the frontal cortex: in vivo microdialysis study in the rat. J Neural Transm Gen Sect 1994; 98: 15–22PubMedCrossRefGoogle Scholar
  6. 6.
    Abe E, Murai S, Saito H, et al. Effects of nefiracetam on deficits in active avpidance response and hippocampal cholinergic and monoaminergic dysfunctions induced by AF64A in mice. J Neural Transm Gen Sect 1994; 95(3): 179–93PubMedCrossRefGoogle Scholar
  7. 7.
    Nabeshima T, Tohyama K, Murase K, et al. Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and Muscarinic receptors induced by cycloheximide. J Pharmacol Exp Ther 1991; 257: 271–5PubMedGoogle Scholar
  8. 8.
    Abe E, Murai S, Saito H, et al. Effects of nefiracetam, a novel pyrrolidone derivative, on brain monoamine metabolisms in mice. J Neural Transm Gen Sect 1992; 90(2): 125–36PubMedCrossRefGoogle Scholar
  9. 9.
    Luthman J, Lindqvist E, Kojima H, et al. Effects of nefiracetam (DM-9384), a pyrrolidone derivative, on brain monoamine systems. Arch Int Pharmacodyn Ther 1994; 328: 125–44PubMedGoogle Scholar
  10. 10.
    Watabe S, Taniguchi K, Kojima H. Improvement of impaired brain monoamine metabolism by the cognition-enhancing agent nefiracetam after microsphere-induced cerebral embolism in rats. Arzneimittel Forschung 1994; 44(2A): 195–8PubMedGoogle Scholar
  11. 11.
    Yoshii M, Watabe S. Enhancement of neuronal calcium channel currents by the nootropic agent, nefiracetam (DM-9384), in NG108-15 cells. Brain Res 1994; 642: 123–31PubMedCrossRefGoogle Scholar
  12. 12.
    Yamada K, Nakayama S, Shiotani T, et al. Possible involvement of the activation of voltage-sensitive calcium channels in the ameliorating effects of nefiracetam on scopolamine-induced impairment of performance in a passive avoidance task. J Pharmacol Exp Ther 1994; 270: 881–92PubMedGoogle Scholar
  13. 13.
    Sakurai T, Ojima H, Yamasaki T, et al. Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1 -pyrrolidinyl)acetamide (DM-9384) on learning and memory in rats. Jpn J Pharmacol 1989; 50: 47–53PubMedCrossRefGoogle Scholar
  14. 14.
    Nabeshima T, Nakayama S, Ichihara K, et al. Effects of nefiracetam on drug-induced impairment of latent learning in mice in a water finding task. Eur J Pharmacol 1994; 255: 57–65PubMedCrossRefGoogle Scholar
  15. 15.
    Nabeshima T, Tohyama K, Kameyama T. Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice. Pharmacol Biochem Behav 1990; 36: 233–6PubMedCrossRefGoogle Scholar
  16. 16.
    Sakurai T, Hatanaka S, Tanaka S, et al. Protective effect of DM-9384, a novel pyrrolidone derivative, against experimental cerebral anoxia. Jpn J Pharmacol 1990; 54: 33–43PubMedCrossRefGoogle Scholar
  17. 17.
    Woodruff-Pak DS, Li Y-T. Nefiracetam (DM-9384): effect on eyeblink classical conditioning in older rabbits. Psychopharmacology 1994; 114: 200–8PubMedCrossRefGoogle Scholar
  18. 18.
    Murasaki M, Inami M, Ishigooka J, et al. Phase I study on DM-9384 (nefiracetam) [in Japanese]. Yakuri to Chiryo 1994; 22: 3539–87Google Scholar
  19. 19.
    Ogura C, Uema T. Effects of nefiracetam (DM-9384) on psychiatric symptoms and event-related potentials in the patients with dementia [in Japanese]. Yakuri to Chiryo 1994; 22: 3625–43Google Scholar
  20. 20.
    Hirata K, Katayama S, Yamazaki K, et al. Electric field distribution of event-related potentials in stroke patients. Brain Topography 1996; 8(3): 279–84PubMedCrossRefGoogle Scholar
  21. 21.
    Sudo K, Hashimoto K, Fujimaki Y, et al. Disposition and metabolism of nefiracetam, a new nootropic agent, in the rat, dog and monkey. Yakuri to Chiryo 1994; 22: 3441–52Google Scholar
  22. 22.
    Fujimaki Y, Sudo K, Hakusui H, et al. Single- and multiple-dose pharmacokinetics of nefiracetam, a new nootropic agent, in healthy volunteers. J Pharm Pharmacol 1992; 44: 750–4PubMedCrossRefGoogle Scholar
  23. 23.
    Fujimaki Y, Sudo K, Hakusui H. Pharmacokinetics of nefiracetam and 3 metabolites in humans and stereoselective hydroxylation of its pyrrolidine ring. Xenobiotica 1993; 23: 61–70PubMedCrossRefGoogle Scholar
  24. 24.
    Ohtomo E, Kogure K, Hirai S, et al. Clinical utility of DM-9384 (nefiracetam) in the treatment of cerebrovascular disorders: dose finding study by double-blind method [in Japanese]. Rinsho Iyaku 1994; 10(7): 1507–47Google Scholar
  25. 25.
    Kobayashi T, Ikeda M, Orishige T, et al. Investigation of DM-9384 (nefiracetam) in a long-term treatment of patients with after-effect of cerebrovascular disorders [in Japanese]. Yakuri to Chiryo 1994; 22: 3645–59Google Scholar
  26. 26.
    Hasegawa T, Shigeno K, Hirata Y, et al. Clinical evaluation of DM-9384 (nefiracetam) in a long-term treatment of patients with sequela of cerebrovascular disorders [in Japanese]. Rinsho Iyaku 1994; 10(9): 2087–106Google Scholar
  27. 27.
    Ohtomo E, Kogure K, Hirai S, et al. Clinical efficacy and safety of DM-9384 (nefiracetam) against after-effects following cerebrovascular disease (phase III study). A placebo-controlled double-blind comparative study [in Japanese]. Igaku Ayumi 1994; 170(9): 777–816Google Scholar
  28. 28.
    Ohtomo E, Kogure K, Hirai S, et al. Clinical utility of DM-9384 (nefiracetam) in patients with aftereffect following cerebrovascular disorders: a comparative double-blind study with idebenone [in Japanese]. Rinsho Iyaku 1994; 10(8): 1871–918Google Scholar
  29. 29.
    Fujikawa K, Akiyama Y, Takayama S. Drug dependence study of the new cognition-enhancing agent nefiracetam in rats. Arzneimittel Forschung 1994; 44(2A): 243–7PubMedGoogle Scholar

Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • Karen L. Goa
    • 1
  • Paul Benfield
    • 1
  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

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