The mGlu(2/3) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate, is anti- and proconvulsant in DBA/2 mice.

Abstract

The anticonvulsant activity of the selective group II metabotropic glutamate receptor (mGlu) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been evaluated in chemoconvulsant and sound-induced models of epileptic seizures in DBA/2 mice. 2R,4R-APDC (> or =10 nmol, intracerebroventricularly (i.c.v.), -15 min) transiently reduced sound-induced seizure activity including clonic seizures to 40% of vehicle at 20 nmol (i.c.v.) and 30% of vehicle at 100 mg/kg (intraperitoneally (i.p.), -15 min). 2R,4R-APDC inhibited clonic seizures induced by the group III mGlu antagonist (R,S)-alpha-methylserine-O-phosphate (2.5 micromol, i.c.v.) when co-injected at 20-40 nmol and inhibited limbic seizure activity induced by the mGlu(1/5) agonist (R,S)-3,5-dihydroxyphenylglycine (1.5 micromol, i.c.v.) when co-injected at 10-40 nmol. A reversal of the anticonvulsant activity of 2R,4R-APDC was observed at (>20 nmol) in each of the chemoconvulsant and sound-induced models of epileptic seizures. 2R,4R-APDC (0.1-1 micromol, i.c.v.) induced stimulus-independent, rapid and dose-dependent clonic seizures. Selective mGlu(2/3) agonists represent a novel class of potential anti-epileptic drugs, however due to the proconvulsant activity observed here, 2R,4R-APDC is obviously limited in this regard.

• Authors: R X Moldrich, A Talebi, P M Beart, A G Chapman, B S Meldrum
• Journal: Neuroscience letters (Neurosci Lett) Vol. 299 Issue 1-2 Pg. 125-9 (Feb 16 2001) ISSN: 0304-3940 [Print] Ireland
• PMID: 11166954 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-aminopyrrolidine-2,4-dicarboxylic acid
• Anticonvulsants
• Convulsants
• Excitatory Amino Acid Agonists
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor 2
• metabotropic glutamate receptor 3
• Proline

Topics

• Animals
• Anticonvulsants (pharmacology)
• Central Nervous System (drug effects, metabolism, physiopathology)
• Convulsants (pharmacology)
• Dose-Response Relationship, Drug
• Epilepsy (chemically induced, drug therapy, physiopathology)
• Excitatory Amino Acid Agonists (pharmacology)
• Female
• Male
• Mice
• Mice, Inbred DBA
• Proline (analogs & derivatives, pharmacology)
• Receptors, Metabotropic Glutamate (agonists, antagonists & inhibitors, metabolism)
• Sound (adverse effects)