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Powerful inhibition of kainic acid seizures by neuropeptide Y via Y5-like receptors

Nature Medicine volume 3, pages 761–764 (1997)Cite this article

Abstract

Neuropeptide Y (NPY) is widely distributed in interneurons of the central nervous system (CNS), including the hippocampus and cerebral cortex, in concentrations exceeding those of any other known neuropeptides1,2. Sequence data comparing different species show that NPY is highly conserved3. This suggests a critical role in regulation of regional neuronal excitability. Kainic acid, a glutamate agonist at kainic acid receptors, causes severe limbic motor seizures culminating in status epilepticus4. We here report that NPY administered into the lateral ventricle is a powerful inhibitor of motor as well as electroencephalographic (EEG) seizures induced by kainic acid. This effect was mediated via receptors with a pharmacological profile similar to the recently cloned rat Y5 receptor5. The present study is the first to demonstrate that NPY possesses anticonvulsant activity. This is consistent with the concept that NPY is an endogenous anticonvulsant and suggests that agonists acting at Y5-like receptors may constitute a novel group of drugs in antiepileptic therapy.

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Authors and Affiliations

  1. Laboratory ofNeuropharmacology, Department of Pharmacology, University of Copenhagen, 3 Blegdamsvej, DK-2200, Copenhagen N, Denmark

    David P.D. Woldbye & Kristian Klemp

  2. Institute of Medical Anatomy, University of Copenhagen, 3 Blegdamsvej, DK-2200, Copenhagen N, Denmark

    Philip J. Larsen

  3. Laboratory for Experimental Neuropsychiatry, University Hospital, Rigshospitalet 0-6234,9 Blegdamsvej, DK-2100, Copenhagen, Denmark

    Torsten M. Madsen & Tom G. Bolwig

  4. Department of Neurobiology, H. LundbeckA/S, 9 Ottiliavej, DK-2500, Copenhagen-Valby, Denmark

    Jens D. Mikkelsen

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  1. David P.D. Woldbye
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  2. Philip J. Larsen
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  3. Jens D. Mikkelsen
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  4. Kristian Klemp
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  5. Torsten M. Madsen
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  6. Tom G. Bolwig
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Woldbye, D., Larsen, P., Mikkelsen, J. et al. Powerful inhibition of kainic acid seizures by neuropeptide Y via Y5-like receptors. Nat Med 3, 761–764 (1997). https://doi.org/10.1038/nm0797-761

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