Anticonvulsant properties of BIBP3226, a non-peptide selective antagonist at neuropeptide Y Y1 receptors

Marco Gariboldi, Mirco Conti, Davide Cavaleri, Rosario Samanin, Annamaria Vezzani

Research output: Contribution to journalArticle

Abstract

Several lines of evidence indicate that neuropeptide Y (NPY)-mediated neurotransmission in the hippocampus is altered by limbic seizures. The functional consequences of this change are still unresolved and clearly depend on the type of NPY receptors involved. We have investigated the role of NPY Y1 receptor subtypes, which are enriched in the dentate area of the hippocampus, on EEG seizures induced by a local injection of 0.04 μg kainic acid in rats. Intrahippocampal administration of 10 μg BIBP3226 (N2- (diphenylacetyl)-N-[(4-hydroxyphenyl)met arginamide), a non-peptide selective antagonist at the NPY Y1 receptors, increased threefold on average (P <0.01) the time to onset of seizures and reduced the number of seizures and the total time in seizures three- and fourfold, respectively (P <0.01). Its inactive S-enantiomer BIBP3435 was ineffective on seizure activity. One microgram [Leu31,Pro34]NPY, an agonist at Y1 receptors, did not modify per se the EEG sequelae induced by kainic acid but it antagonized the anticonvulsant effect of BIBP3226. These results indicate that NPY Y1 receptors in the hippocampus are involved in epileptic phenomena and suggest that selective Y1 receptor antagonists may be of value for attenuating limbic seizures.

Original languageEnglish
Pages (from-to)757-759
Number of pages3
JournalEuropean Journal of Neuroscience
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 1998

Keywords

  • Dentate gyrus
  • EEG
  • Epilepsy
  • Hippocampus
  • Kainic acid

ASJC Scopus subject areas

  • Neuroscience(all)

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