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.
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Authors | P J Attwell, A Koumentaki, A S Abdul-Ghani, M J Croucher, H F Bradford |
Journal | Brain research
(Brain Res)
Vol. 787
Issue 2
Pg. 286-91
(Mar 23 1998)
ISSN: 0006-8993 [Print] Netherlands |
PMID | 9518652
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 1998 Elsevier Science B.V. |
Chemical References |
- Anticonvulsants
- Excitatory Amino Acid Agonists
- Monosaccharide Transport Proteins
- Receptors, Metabotropic Glutamate
- Glutamic Acid
- Proline
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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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