<Orignal>The Relationship Between the Pharmacological Effects of Benzodiazepines and Their in vivo Binding Sites in the Brain of Rats.

Abstract

ベンゾジアゼピン系薬剤とフェノバルビタール薬理作用と脳内分布との関連を生体内で調べるため, 60匹のラット(体重470～480 g)を3郡に分け, 3^H-diazepam, 3^H-flunitrazepamまたは3^H-ohenobarbital 5μciを投与した。それぞれのグループのラットは薬剤の静脈内投与後3分, 10分, または40分の時点で断頭し, 各組織の放射能を測定し, d.p.m/g・tissueに換算した。この結果, 3^H-diazepamの放射線量は脳幹および視床下部で他の大脳皮質に比べ有意に高かった。また, 3^H-phenobarbitalの脳内濃度は換与後40分経ってもほとんど低下しなかった。これらの結果はベンゾジアゼピン系薬剤の薬理作用との密接な関連があり, in-vitroで証明されたbenzobiazepinereceotorはin-vivoではあまり重要な意味を持たない可能性があることを示唆している。To compare the in vitro pharmacological effect and in the brain distribution of benzodiazepines and phenobarbital, three group of sixty anesthetized rats (470～480g) were administered 5μCi of 3^H-diazepam, 3^H-flunitrazepam or 3^H-phenobarbital. The rats were decapitated 3, 10, or 40 minutes after the intravenous injection of these drugs. Radioactivity of the tissue was measured and calculated as d.p.m./g. tissue. 3^H-diazepam radioactivity in the brainstem and hypothalamus was significantly higher than in the brain cortex 3 and 10 minutes after the injection. 3^H-flunitrazepam radioactivity in the brain cortex was higher than in other regions. There was no significant decrease in 3^H-phenobarbital brain concentration, even 40 minutes after injection. The distribution of benzodiazepine is closely related with its pharmacological effect, and this suggests that in vitro benzodiazepine binding sites are not responsible for the pharmacological action in vivo