Antiepileptogenic and anticonvulsive actions of levetiracetam in a pentylenetetrazole kindling model.
Levetiracetam (LEV) is a unique antiepileptic drug that preferentially interacts with synaptic vesicle protein 2A (SV2A). To evaluate the antiepileptogenic action of LEV, we studied its effects on the development and acquisition of pentylenetetrazole (PTZ) kindling and compared them to those of sodium valproate (VPA). Anticonvulsive actions of LEV in PTZ-kindled animals were also determined. LEV did not affect PTZ seizures in naïve animals even at high doses (approximately 300 mg/kg, i.p.). However, combined treatment of LEV (30 and 100 mg/kg, i.p.) with PTZ significantly suppressed the development and acquisition of PTZ kindling. In addition, LEV at relatively low doses (3-30 mg/kg, i.p.) inhibited PTZ-evoked seizures in fully kindled animals. In contrast to LEV, VPA at sub-anticonvulsive doses (30 and 100 mg/kg, i.p.) failed to prevent the development of PTZ kindling and its anticonvulsive potency was similar in PTZ-kindled and naïve mice. The present study shows that LEV contrasts VPA by preventing the development of PTZ kindling and inhibiting seizures selectively in kindled animals.
Ohno
Yukihiro
Y
Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. yohno@gly.oups.ac.jp
Ishihara
Shizuka
S
Terada
Ryo
R
Serikawa
Tadao
T
Sasa
Masashi
M
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003292:Convulsants; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000187:drug effects*; D000077287:Levetiracetam; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology
D000927:Anticonvulsants; D003292:Convulsants; D000077287:Levetiracetam; D014635:Valproic Acid; D010433:Pentylenetetrazole; D010889:Piracetam