Influence of SIB 1893, a selective mGluR5 receptor antagonist, on the anticonvulsant activity of conventional antiepileptic drugs in two models of experimental epilepsy.
SIB 1893, a non-competitive antagonist of group I metabotropic glutamate receptor subtype 5, administered at doses ranging from 0.25 to 10 mg/kg, failed to influence pentetrazole-induced convulsions in mice. Moreover, SIB 1893 (10 and 20 mg/kg) did not affect the protective action of valproate, ethosuximide, phenobarbital and clonazepam in this test. Similarly, the mGluR5 antagonist did not modulate the antiseizure activity of carbamazepine, diphenylhydantoin and phenobarbital against maximal electroshock in mice. The combined treatment of SIB 1893 with conventional antiepileptic drugs did not lead to motor impairment. Long-term memory disturbances were observed only in the case of the combination of SIB 1893 with phenobarbital.
Borowicz
Kinga K
KK
Department of Pathophysiology, Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland.
Piskorska
Barbara
B
Łuszczki
J
J
Czuczwar
Stanisław J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001362:Avoidance Learning / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology / Q000627:therapeutic use; D002998:Clonazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004338:Drug Combinations; D004558:Electric Stimulation / Q000379:methods*; D004597:Electroshock / Q000379:methods; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology*; D005013:Ethosuximide / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000009:adverse effects; D010634:Phenobarbital / Q000494:pharmacology / Q000627:therapeutic use; D010672:Phenytoin / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
D000927:Anticonvulsants; D004338:Drug Combinations; C578936:Grm5 protein, mouse; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C120148:SIB 1893; D002220:Carbamazepine; D002998:Clonazepam; D005013:Ethosuximide; D014635:Valproic Acid; D010672:Phenytoin; D010433:Pentylenetetrazole; D010634:Phenobarbital