| RRC ID |
80
|
| 著者 |
Amano T, Aihua Z, Matsubayashi H, Seki T, Serikawa T, Sasa M, Sakai N.
|
| タイトル |
Antiepileptic effects of single and repeated oral administrations of S-312-d, a novel calcium channel antagonist, on tonic convulsions in spontaneously epileptic rats.
|
| ジャーナル |
J Pharmacol Sci
|
| Abstract |
We investigated the effects of single and repeated administrations of S-312-d (methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)-thieno-[2,3-b]pyridine-5-carboxylate), a newly synthesized L-type Ca(2+)-channel blocker, on tonic convulsions and absence-like seizures in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a genetically based animal model of human epilepsy. Single oral administrations of S-312-d dose-dependently inhibited tonic convulsions and the effects lasted for more than 2 h, although they did not attenuate the absence-like seizures. We also examined the effects of repeated administrations of S-312-d at 1 mg/kg once a day for 4 days on SER. A significant decrease in the number and total duration of tonic convulsions was observed 45 and 75 min after the first administration of the drug, respectively. The effects lasted for 24 h without changes in the background EEG or blood pressure. This inhibitory effect on the tonic convulsions was gradually strengthened by subsequent daily administrations of S-312-d and lasted for 3 days after the cessation of drug treatment. In contrast, the repeated treatment with S-312-d did not influence absence-like seizures of SER. These results suggest that S-312-d is a candidate drug that has antiepileptic effects against the convulsive seizures in human epilepsy.
|
| 巻・号 |
95(3)
|
| ページ |
355-62
|
| 公開日 |
2004-7-1
|
| DOI |
10.1254/jphs.fp0040233
|
| PII |
JST.JSTAGE/jphs/FP0040233
|
| PMID |
15272212
|
| MeSH |
Administration, Oral
Animals
Anticonvulsants / administration & dosage
Anticonvulsants / pharmacology
Anticonvulsants / therapeutic use*
Calcium Channel Blockers / administration & dosage
Calcium Channel Blockers / pharmacology
Calcium Channel Blockers / therapeutic use*
Dihydropyridines / administration & dosage
Dihydropyridines / pharmacology
Dihydropyridines / therapeutic use*
Electroencephalography
Epilepsy, Absence / drug therapy
Epilepsy, Absence / physiopathology
Epilepsy, Generalized / drug therapy*
Epilepsy, Generalized / physiopathology
Female
Male
Rats
Time Factors
|
| IF |
2.835
|
| 引用数 |
6
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| ラット |
SER/Kyo(strainID=28) |
