Project/Area Number |
05670108
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
General pharmacology
|
Research Institution | Nihon University |
Principal Investigator |
ITO Yoshihisa Nihon Univ.Pharmacy, Full-time lecturer, 薬学部, 専任講師 (50151551)
|
Co-Investigator(Kenkyū-buntansha) |
ISHIGE Kumiko Nihon Univ.Pharmacy, Assistant lecturer, 薬学部, 助手 (40212873)
|
Project Period (FY) |
1993 – 1994
|
Project Status |
Completed (Fiscal Year 1994)
|
Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
Keywords | benzodiazepine receptors / Ro 15-4513 / imidazobenzodiazepines / ethanol / pentylenetetrazole / Ro19-4603 / フェノバルビタール / 抗けいれん作用 / ジアゼパム非感受性 / [^3H]Ro15-4513 / 受容体結合実験 / ラット小脳 / 小脳顆粒細胞初代培養系 |
Research Abstract |
In order to characterize diazepam-insensitive benzodiazepine receptors, effects of various imidazobenzodiazepine compounds on [^3H] Ro 15-4513 binding and ethanolinduced anticonvulsant activity were investigated. Scatchard analysis of [^3H] Ro 15-4513 binding in the presence of excess amount of diazepam revealed linear plots in rat brain and cultured cerebellar granule cells. Although some imidazobenzodiazepine compounds such as flumazenil (Ro 15-1788) and Ro 19-4603, and a pyrazoloquinoline compound, CGS 8216, showed high affinity for the diazepam-insensitive sites, classical benzodiazepines and beta-carboline analogues such as methyl-6,7-dimethyl-4-ethyl-beta-carboline-3-carboxylate (DMCM) and FG 7142 did not displace the binding. Treatment of mice with pentylenetetrazole (60mg/kg, i.p.) exhibited chronic seizures within 2 to 3 min after administration in mice and this effect was suppressed by ethanol (1.5g/kg) . Ro 15-4513 (4mg/kg) and Ro 19-4603 (4mg/kg) antagonized the anticonvulsant action of ethanol. However, these compounds showed weak antagonistic effects on anticonvulsant activity of phenobarbital (50mg/kg) . These results suggest that diazepm-insensitive benzodiazepine receptors have high affinity for imidazobenzodiazepine compounds such as Ro 15-4513 and Ro 19-4603 and that the receptors play an important role in reversal of acute effects of ethanol by these imidazobenzodiazepine compounds.
|