Anticonvulsant effects of dipotassium clorazepate on hippocampal kindled seizures in rats.
We examined the anticonvulsant properties of dipotassium clorazepate (DC) against hippocampal kindled seizures in rats. Adult male Wistar rats were subjected to kindling 1 week after the implantation of electrodes. After five stage 5 seizures were induced, the generalized convulsion triggering threshold (GST) was determined. Dipotassium clorazepate was administered intraperitoneally in rats that showed two stable stage 5 seizures induced at the GST current intensity. Dipotassium clorazepate at doses of 1 mg/kg or more produced an anticonvulsant effect, but did not readily suppress limbic seizures. Dipotassium clorazepate did not completely suppress after-discharges (AD) even at the highest dose, which was 5 mg/kg. Moreover, raised stimulus intensity failed to affect its efficacy as an anticonvulsant. The results of the present study suggest that DC has a modest anticonvulsant potency. It is reasonable to assume that its anticonvulsant efficacy is primarily due to attenuation of AD propagation rather than the raising of the seizure triggering threshold at the kindling focus.
Department of Psychiatry, Kikuchi National Hospital, Kumamoto, Japan.
K
K
Amano
J
J
Takamatu
H
H
Kaneyama
C
C
Miyazaki
M
M
Deshimaru
S
S
Sumiyoshi
A
A
Ogata
T
T
Miyakawa
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003009:Clorazepate Dipotassium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007263:Infusions, Parenteral; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy
D000927:Anticonvulsants; D003009:Clorazepate Dipotassium