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Specific group II metabotropic glutamate receptor activation inhibits the development of kindled epilepsy in rats.

Abstract
The effects of intracerebral administration of the group II metabotropic glutamate receptor agonist, 2R,4R-APDC, were tested on both the development of amygdaloid kindling and on fully developed stage 5 amygdala kindled seizures. The development of amygdaloid kindling was significantly retarded in 2R,4R-APDC (10 nmol in 0.5 microl) treated animals compared to control animals over a period of 8 days. At a low dose, 2R,4R-APDC (0.1 nmol) caused a 42.5+/-26.6% increase of the generalised seizure threshold in fully kindled animals. As higher doses were administered, however, the changes in generalised seizure threshold were less marked, and even a small decrease in the threshold was seen (-19.6+/-5.36% at 10 nmol). The agonist 2R,4R-APDC inhibited depolarization-induced release of [3H]d-aspartate from cortical synaptosomes with an IC50 value of 0. 29 microM. This effect was maximal at 1 microM, and decreased with dose thereafter. These findings suggest that the selective activation of the group II metabotropic glutamate receptors by agonists such as 2R,4R-APDC may be of therapeutic potential in the treatment of seizure disorders.
AuthorsP J Attwell, A Koumentaki, A S Abdul-Ghani, M J Croucher, H F Bradford
JournalBrain research (Brain Res) Vol. 787 Issue 2 Pg. 286-91 (Mar 23 1998) ISSN: 0006-8993 [Print] Netherlands
PMID9518652 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 1998 Elsevier Science B.V.
Chemical References
  • Anticonvulsants
  • Excitatory Amino Acid Agonists
  • Monosaccharide Transport Proteins
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid
  • Proline
Topics
  • Animals
  • Anticonvulsants (pharmacology)
  • Brain (pathology)
  • Dose-Response Relationship, Drug
  • Epilepsy (pathology, prevention & control)
  • Excitatory Amino Acid Agonists (pharmacology)
  • Glutamic Acid (metabolism)
  • Kindling, Neurologic (drug effects, physiology)
  • Male
  • Monosaccharide Transport Proteins
  • Proline (analogs & derivatives, pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate (agonists)
  • Synaptosomes (drug effects, metabolism)

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