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Effects of Nefiracetam, a Novel Pyrrolidone‐type Nootropic Agent, on the Amygdala‐kindled Seizures in Rats
Author(s) -
Kitano Yutaka,
Komiyama Chika,
Makino Mitsuhiro,
Kasai Yoshio,
Takasuna Kiyoshi,
Kinoshita Masakazu,
Yamazaki Osamu,
Takazawa Akira,
Yamauchi Toshio,
Sakurada Shinobu
Publication year - 2005
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2005.00261.x
Subject(s) - amygdala , kindling , anticonvulsant , basolateral amygdala , epilepsy , nootropic , pharmacology , psychology , anesthesia , neuroscience , chemistry , medicine
Summary: Purpose: Nefiracetam (NEF) is a novel pyrrolidonetype nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition‐enhancing effects. The present study focused on the effects of NEF in amygdala‐kindled seizures and its potential for antiepileptic therapy. Methods: Effects of NEF on fully amygdala‐kindled seizures and development of amygdala‐kindled seizures were investigated in rats and compared with those of levetiracetam (LEV), a pyrrolidone‐type antiepileptic drug (AED). Results: In fully amygdala‐kindled rats, NEF (25, 50, and 100 mg/kg, p.o.) decreased afterdischarge induction, afterdischarge duration, seizure stage, and motor seizure duration in a dose‐dependent manner. LEV (25, 50, and 100 mg/kg, p.o.) had no effects on afterdischarge induction and slightly decreased afterdischarge duration, whereas it markedly decreased seizure stage and motor seizure duration. In contrast to the results in fully amygdala‐kindled rats, NEF (25 and 50 mg/kg/day, p.o.) had few or no effects on the development of amygdala‐kindled seizures. As well as fully amygdala‐kindled seizures, LEV (50 mg/kg/day, p.o.) markedly inhibited the development of behavioral seizures without reducing daily afterdischarge duration. Conclusions: Although NEF possesses potent anticonvulsant effects on fully amygdala‐kindled seizures, it has few or no effects on the development of amygdala‐kindled seizures. LEV shows marked anticonvulsant effects on both phases of kindling. In fully amygdala‐kindled rats, NEF inhibits both electroencephalographic and behavioral seizures, whereas LEV inhibits only behavioral seizures. This double dissociation suggests that NEF has a distinct anticonvulsant spectrum and mechanisms from those of LEV.