THE BENZODIAZEPINE RECEPTOR AND RECEPTOR TOLERANCE PRODUCED BY CHRONIC TREATMENT OF DIAZEPAM
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概要
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A characterization of the benzodiazepine receptor in vivo was carried out utilizing the up-and-down method for a quantitative determination of the maximal seizure threshold to diazepam. Wistar-Imamichi male rats of 21 days of age were used. The drug concentration in the brain at the steady-state was measured with radiolabeled diazepam. A kinetic analysis for the dose-response relation obtained gave 2.2 μM and 1.6 for the Kd and n, respectively, in the Langmuir adsorption isotherm. The results suggested the existence of a hitherto undiscovered endogenous ligand(s) suppressing the binding of benzodiazepine to the receptor, as compared with those in the in vitro binding-assay reported by other investigators. A chronic pretreatment with diazepam once a day for 13 days (0.2 and 2 mg/kg, s.c.) produced receptor tolerance, but did not affect the amount of the seizure threshold unless the drug was acutely administered 10 min before the electric shock. These results supported the argument that two distinct entities exist for both GABA and benzodiazepine recognition sites which are closely related to each other in their functioning.
- 社団法人 日本薬理学会の論文
著者
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Fujii Tomoko
Department Of Biology School Of Education Waseda University
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HIRONAKA Tetsuji
Department of Pharmacology, Teikyo University School of Medicine
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FUCHINO Katsuhiro
Department of Pharmacology, Teikyo University School of Medicine
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