Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice.
The effects of topiramate, a novel antiepileptic drug, on tonic and absence-like seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) and on sound-induced seizures in DBA/2 mice were investigated. Topiramate (20 and 40 mg/kg i.p.) inhibited both tonic and absence-like seizures in a dose-dependent manner, whereas phenytoin (20 mg/kg i.p.) and zonisamide (40 mg/kg i.p.) inhibited only the tonic seizures. The inhibitory effects of topiramate on absence-like seizures were antagonized by pretreatment with haloperidol (0.5 mg/kg i.p.), but those on the tonic seizures remained unaffected. Topiramate inhibited sound-induced seizures in DBA/2 mice (ED50 = 8.6 mg/kg p.o.). These findings suggest that topiramate may be effective for treatment of both convulsive and absence seizures of human epilepsy. The inhibitory effect of topiramate on absence-like seizures in SER may be mediated through the central dopaminergic system.
Nakamura
J
J
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Tamura
S
S
Kanda
T
T
Ishii
A
A
Ishihara
K
K
Serikawa
T
T
Yamada
J
J
Sasa
M
M
D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000235:genetics / Q000517:prevention & control*; D004832:Epilepsy, Absence / Q000235:genetics / Q000517:prevention & control; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D012640:Seizures / Q000517:prevention & control*; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D006220:Haloperidol