Ethosuximide suppresses seizures and lethality induced by picrotoxin in developing rats.
The action of ethosuximide (125 or 250 mg/kg, IP) against picrotoxin-induced seizures (3-6 mg/kg, IP) was assessed in rats 12, 18, 25, and 90 days old. In 18-day-old and older controls, picrotoxin regularly elicited clonic seizures; tonic-clonic seizures were induced in all age categories with high consequent mortality. Only the higher dose of ethosuximide (250 mg/kg) increased the latency of clonic seizures in 18- and 25-day-old pups. Tonic-clonic seizures were delayed by ethosuximide in 12-, 18-, and 90-day-old rats. Picrotoxin-induced lethality was suppressed only in 18- and 90-day-old rats by the 250-mg/kg dose of ethosuximide. In contrast, ethosuximide pretreatment increased the incidence of clonic seizures in 12-day-old rats. The results suggest that only high doses of ethosuximide can suppress clonic seizures, and this action is not consistent. Tonic-clonic seizures probably have model-specific sensitivity to ethosuximide because in previous studies ethosuximide completely suppressed pentylenetetrazol-induced tonic-clonic seizures but had no effect on kainic acid-induced tonic-clonic seizures. The suppression of mortality rates is probably due to nonspecific effects of high doses of ethosuximide.
Velísková
J
J
Department of Physiology, 3rd Medical Faculty, Charles University, Prague, Czechoslovakia.
Velísek
L
L
Mares
P
P
Rokyta
R
R
Micianiková
D
D
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004831:Epilepsies, Myoclonic / Q000517:prevention & control; D004830:Epilepsy, Tonic-Clonic / Q000517:prevention & control; D005013:Ethosuximide / Q000494:pharmacology*; D008297:Male; D010433:Pentylenetetrazole; D010852:Picrotoxin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D000927:Anticonvulsants; D005013:Ethosuximide; D010433:Pentylenetetrazole; D010852:Picrotoxin