Attenuation of in vivo and in vitro seizure activity using the adenosine agonist, metrifudil

S. E. Krahl, L. M. Treas, J. D. Castle, Robert F Berman

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Adenosine and other adenosine receptor agonists have been shown to inhibit seizures in a variety of in vivo and in vitro models. In the present study, the anticonvulsive effects of the partially selective A(2a) agonist, N-[(2-methylphenyl)methyl]-adenosine (metrifudil), were examined using both the amygdala kindling and 0-Mg++-induced bursting hippocampal slice seizure models. Fully amygdala-kindled rats were injected with 1, 10, or 25 mg/kg (2.7, 27.0, or 67.4 μmol/kg) ip metrifudil, or vehicle (dimethyl sulfoxide), 20 min prior to receiving the kindling stimulus. Metrifudil significantly reduced after-discharge duration in a dose-related fashion compared to vehicle injections. After-discharge threshold and behavioral seizure stage were not significantly affected. In the in vitro hippocampal slice preparation, stimulation of Schaffer collateral axons under 0-Mg++ conditions resulted in spontaneous and evoked epileptiform burst activity in the CA1 region. The addition of 1, 10, or 100 μM metrifudil to the 0-Mg++ media abolished this epileptiform activity in a concentration-related fashion. These findings indicate that the adenosine agonist, metrifudil, may have anticonvulsive properties, and are in support of the premise that the adenosine system plays an anticonvulsive role in the central nervous system.

Original languageEnglish (US)
Pages (from-to)30-34
Number of pages5
JournalDrug Development Research
Volume34
Issue number1
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • Amygdala
  • Anticonvulsant
  • Hippocampus
  • Kindling
  • Slice

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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