1994 Fiscal Year Final Research Report Summary
Studies on diazepam-insensitive benzodiazepine receptors
| Project/Area Number |
05670108
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Nihon University |
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Principal Investigator |
ITO Yoshihisa Nihon Univ.Pharmacy, Full-time lecturer, 薬学部, 専任講師 (50151551)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIGE Kumiko Nihon Univ.Pharmacy, Assistant lecturer, 薬学部, 助手 (40212873)
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| Project Period (FY) |
1993 – 1994
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| Keywords | benzodiazepine receptors / Ro 15-4513 / imidazobenzodiazepines / ethanol / pentylenetetrazole |
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| 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.
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