Neuroprotective effects of the GABA(A) receptor partial agonist U- 101017 in 3-acetylpyridine-treated rats

Vimala H. Sethy, Haiyan Wu, Jo A. Oostveen, Edward D. Hall

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The neuroprotective effects of U-101017, [7-chloro-5-[cis-3,5- dimethylpiperazine)carbonyl][-imidazole[1,5a]quinoline-3-carboxylate], a GABA(A), receptor partial agonist, were investigated in 3-acetylpyridine (3- AP) treated Wistar rats. A significant (P < 0.01) reduction in both cGMP and ATP in the cerebellum was observed at 96 h after treatment with 3-AP (500/μmol/kg i.p.). Oral administration of U-101017 before and after treatment with 3-AP significantly attenuated 3-AP-induced decreases in cGMP and ATP, and this effect was dose related. Consistent with the neurochemical effect, U-101017 prevented 3-AP-induced loss of motor coordination. Treatment with U-101017 partially, but significantly (P < 0.01) prevented the loss of inferior olivary neurons. U-101017 had no significant effect on body temperature. Thus, hypothermia was not involved in neuroprotective effects of U-101017. Co-administration of flumazenil with each treatment of U-101017 blocked the neuroprotective effect of U-101017, indicating that it mediated neuroprotection via the benzodiazepine binding sites on the GABA(A) receptor complex. Delayed administration of U-101017 at various time intervals after treatment with 3-AP demonstrated a significant neuroprotective effect even at 8 h, suggesting that this drug has a wide therapeutic window.

Original languageEnglish
Pages (from-to)45-49
Number of pages5
JournalNeuroscience Letters
Issue number1
StatePublished - May 30 1997

Bibliographical note

Copyright 2007 Elsevier B.V., All rights reserved.


  • 3-Acetylpyridine
  • Neuroprotective effects
  • γ-Aminobutyric acid

ASJC Scopus subject areas

  • General Neuroscience


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