Anticonvulsant effect of (RS)-1-aminoindan-1,5-dicarboxylic acid on pentetrazol-induced kindled seizures in mice.
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.
Watanabe
Yusuke
Y
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Kaida
Yuko
Y
Takechi
Kenshi
K
Kamei
Chiaki
C
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D018682:GABA Agents / Q000494:pharmacology*; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010424:Pentobarbital; D010433:Pentylenetetrazole; D018079:Receptors, GABA / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
C095756:1-aminoindan-1,5-dicarboxylic acid; D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D007189:Indans; D018079:Receptors, GABA; D010424:Pentobarbital; D010433:Pentylenetetrazole