SIB 1893, a selective mGluR5 receptor antagonist, potentiates the anticonvulsant activity of oxcarbazepine against amygdala-kindled convulsions in rats.
SIB 1893 (a non-competitive antagonist of group I metabotropic glutamate receptors), given at 40 mg/kg (but not at 20-30 mg/kg), shortened the afterdischarge duration in amygdala-kindled rats, being ineffective on other seizure parameters - seizure severity, seizure duration, and afterdischarge threshold. Oxcarbazepine (at 7.5 mg/kg, but not at 5 mg/kg), a newer antiepileptic drug, reduced seizure severity, seizure and afterdischarge durations. When combined at ineffective doses in amygdala kindling, SIB 1893 at 20 or 30 mg/kg and oxcarbazepine at 5 mg/kg, significantly reduced seizure and afterdischarge durations. The results indicate that combinations of oxcarbazepine with antagonists of group I metabotropic glutamate receptors may offer a novel therapeutic approach in cases of drug-resistant epilepsy.
Borowicz
Kinga K
KK
Department of Pathophysiology, Skubiszewski Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland. czuczwarsj@yahoo.com
Łuszczki
Jarogniew J
JJ
Czuczwar
Stanisław J
SJ
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004357:Drug Synergism; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D000078330:Oxcarbazepine; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C120148:SIB 1893; D002220:Carbamazepine; D000078330:Oxcarbazepine