Anticonvulsant effect of (RS)-1-aminoindan-1,5-dicarboxylic acid on pentetrazol-induced kindled seizures in mice.

Abstract

The present study was undertaken to clarify the effect of group I metabotropic glutamate receptor (mGluR) antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) on pentetrazol-induced kindled seizures. The mechanism of the anticonvulsant effect of AIDA was also studied. Mice were anesthetized with pentobarbital; the electrodes and guide cannula were chronically implanted into the cortex and lateral ventricle. In order to induce kindling, pentetrazol at a dose of 40 mg/kg was injected intraperitoneally once every 48 h. Behavioral and electroencephalographic (EEG) seizures were observed for 20 min following pentetrazol administration. Intracerebroventricular (i.c.v.) injection of AIDA (1000 nmol/site) resulted in a significant inhibitory effect on pentetrazol-induced kindled seizures, and this effect was antagonized by a group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-3,5-DHPG). The effect of AIDA (200 nmol/site) on pentetrazol-induced kindled seizures was augmented by the simultaneous use of gamma-aminobutyric acid (GABA) mimetic drugs, such as NNC-711 and diazepam. Moreover, the effect of AIDA (1000 nmol/site) on pentetrazol-induced kindled seizures was antagonized by a GABA(A) receptor antagonist, bicuculline and a GABA(C) receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA). It can be concluded that AIDA had an anticonvulsant effect on pentetrazol-induced kindled seizures, which was partially mediated by the GABAergic mechanism through GABA(A) and GABA(C) receptors.

• Authors: Yusuke Watanabe, Yuko Kaida, Kenshi Takechi, Chiaki Kamei
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 33 Issue 4 Pg. 647-52 ( 2010) ISSN: 1347-5215 [Electronic] Japan
• PMID: 20410600 (Publication Type: Journal Article)

Chemical References

• 1-aminoindan-1,5-dicarboxylic acid
• Anticonvulsants
• Excitatory Amino Acid Antagonists
• GABA Agents
• Indans
• Receptors, GABA
• Pentobarbital
• Pentylenetetrazole

Topics

• Animals
• Anticonvulsants (pharmacology, therapeutic use)
• Brain (drug effects)
• Excitatory Amino Acid Antagonists (pharmacology, therapeutic use)
• GABA Agents (pharmacology)
• Indans (pharmacology, therapeutic use)
• Kindling, Neurologic (drug effects)
• Male
• Mice
• Mice, Inbred ICR
• Pentobarbital
• Pentylenetetrazole
• Receptors, GABA (metabolism)
• Seizures (chemically induced, drug therapy, metabolism)