Effects of conventional antiepileptic drugs in a model of spontaneous recurrent seizures in rats.
Pilocarpine (PILO) induces in rats limbic seizures that become secondarily generalized and evolve to status epilepticus (SE). Spontaneous recurrent seizures are registered during the long-term period following the systemic administration of PILO in rats. EEG, behavioral, and pathological features resemble those of complex partial seizures. The antiepileptic drugs (AEDs) diazepam, phenobarbital (PB), valproic acid (VPA) and trimethadione protect against PILO-induced SE while phenytoin (PHT) and carbamazepine (CBZ) are ineffective. Studies with AEDs on spontaneous seizures (chronic period) of this model have not yet been established. We now report the effects of different AEDs on spontaneous seizures. Male Wistar rats were subjected to PILO-induced SE. Following recovery from SE animals were daily observed in order to detect spontaneous seizures and to establish the baseline seizure frequency. PB 40 mg/kg, PHT 100 mg/kg, CBZ 120 mg/kg, VPA (450 mg/kg and 600 mg/kg) and ethosuximide (ETX) 400 mg/kg were given daily to epileptic rats for two weeks during the spontaneous recurrent seizures period. PB, CBZ and PHT were effective against spontaneous seizures. VPA was also effective against spontaneous seizures at the dose of 600 mg/kg and ETX was inactive against these seizures. Such pharmacological profiles correlate well with complex partial seizures. The results indicate that spontaneous recurrent seizures after PILO-induced SE may be a useful model for finding new AEDs with better efficacy against complex partial seizures. The use of animal models that share both pharmacological and phenomenological features with human epilepsy might improve their predictive value for specific types of human epilepsy.
Leite
J P
JP
Departamento de Neurologia e Neurocirurgia, Escola Paulista de Medicina, São Paulo, Brazil.
Cavalheiro
E A
EA
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D017029:Epilepsy, Complex Partial / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013226:Status Epilepticus / Q000139:chemically induced
D000927:Anticonvulsants; D010862:Pilocarpine