Effects of Nefiracetam, a novel pyrrolidone-type nootropic agent, on the amygdala-kindled seizures in rats.
OBJECTIVE
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.
Kitano
Yutaka
Y
New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo. kitanpms@daiichipharm.co.jp
Komiyama
Chika
C
Makino
Mitsuhiro
M
Kasai
Yoshio
Y
Takasuna
Kiyoshi
K
Kinoshita
Masakazu
M
Yamazaki
Osamu
O
Takazawa
Akira
A
Yamauchi
Toshio
T
Sakurada
Shinobu
S
D000284:Administration, Oral; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data; D017029:Epilepsy, Complex Partial / Q000188:drug therapy; D006801:Humans; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D000077287:Levetiracetam; D008297:Male; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*
D000927:Anticonvulsants; D018697:Nootropic Agents; D011760:Pyrrolidinones; C058876:nefiracetam; D000077287:Levetiracetam; D010889:Piracetam