Conventional anticonvulsant drugs in the guinea-pig kindling model of partial seizures: effects of repeated administration.
This study addressed the anticonvulsant effects of repeated administration of phenytoin, carbamazepine, phenobarbital, valproate, and ethosuximide in kindled guinea-pigs in order to further substantiate this novel model of partial seizures for the screening of future anticonvulsant drugs. Behavioral toxic effects were assessed at 30 min following drug administration using scores on a sedation/muscle relaxation rating index. In response to suprathreshold stimulation, the anticonvulsant efficacy of the drugs were evaluated from measurements of afterdischarge duration (ADD) and behavioral seizure severity (SS) during a repeated drug treatment schedule in kindled guinea-pigs. All drugs exerted slight to moderate sedative effects in guinea-pigs on our rating index. We found that phenytoin, carbamazepine, and phenobarbital exhibited effective anticonvulsant properties in kindled guinea-pigs by reducing both ADD and SS. We found that valproate consistently reduced ADD throughout the treatment schedule but failed to significantly reduce SS. Lastly, ethosuximide failed to exhibit effective anticonvulsant properties. Our results indicate that the guinea-pig kindling model correctly predicted the actions of these common anticonvulsant drugs in the treatment of partial seizures. Guinea-pig amygdala kindling appears to serve as a useful and valid model for partial epilepsy.
Gilbert
Trevor H
TH
Centre for Psychology, Athabasca University, 1 University Drive, T9S 3A3, Athabasca, AB, Canada. trevorg@athabascau.ca
Teskey
G Campbell
GC
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002220:Carbamazepine / Q000009:adverse effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation / Q000009:adverse effects; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D005013:Ethosuximide / Q000009:adverse effects; D005260:Female; D006168:Guinea Pigs; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010634:Phenobarbital / Q000009:adverse effects; D010672:Phenytoin / Q000009:adverse effects; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013045:Species Specificity; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects
D000927:Anticonvulsants; D002220:Carbamazepine; D005013:Ethosuximide; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital