Effect of felbamate and its combinations with conventional antiepileptics in amygdala-kindled rats.
We investigated the effect of felbamate, administered singly and in combination with carbamazepine, phenobarbital, phenytoin or clonazepam, on various behavioral and electrographic correlates of seizures in amygdala-kindled rats. Felbamate (5 or 10 mg/kg) significantly increased afterdischarge threshold, shortened seizure and afterdischarge durations but remained without effect on seizure severity. Furthermore, the combination of felbamate (2.5 mg/kg) with carbamazepine (7.5 mg/kg; both drugs at their subeffective doses), was associated with the reduction in seizure severity and afterdischarge duration. In relation to the afterdischarge duration, the antiseizure potency of felbamate and carbamazepine, in combination, was comparable with that of carbamazepine (10 mg/kg) administered alone. Neither carbamazepine (7.5 and 10 mg/kg) nor felbamate (2.5-10 mg/kg) affected seizure severity, whereas the combined administration of felbamate (2.5 mg/kg) with carbamazepine (7.5 mg/kg) led to significant reduction in seizure severity from the fifth to the third stage of Racine's scale. Among the conventional antiepileptic drugs evaluated in this study, only valproate (100 mg/kg) and clonazepam (0.1 mg/kg) exerted similar action on seizure severity. However, the combinations of felbamate (2.5 mg/kg), with subeffective doses of valproate, phenobarbital, phenytoin or clonazepam, were not associated with any protective action. As blood and brain felbamate and carbamazepine concentrations were unaffected, a pharmacokinetic interaction can be excluded and a pharmacodynamic interaction concluded. These data suggest that felbamate and carbamazepine, administered in combination, may be useful in patients with drug-resistant partial epilepsy.
Borowicz
K K
KK
Department of Pathophysiology, Lublin Medical University, Jaczewskiego 8, Lublin 20-090, Poland. kornel@asklepios.am.lublin.pl
Ratnaraj
N
N
Patsalos
P N
PN
Czuczwar
S J
SJ
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D000078328:Felbamate; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate