Nonlinear relationship between benzodiazepine receptor occupancy and glucose metabolic response in the conscious mouse brain in vivo
In: The Journal of pharmacology and experimental therapeutics, Jg. 251 (1989-10-01), Heft 1
Online
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Zugriff:
To evaluate the relationship between the pharmacological effect of benzodiazepine (BZP) and BZP receptor (BZP-R) binding in the conscious mouse brain, a response of the local cerebral metabolic rate of glucose utilization (GU) to clonazepam (CNZ) was measured as an index for the pharmacological effect. Two glucose analogs (3-O-[3H]methylglucose and 2-[14C]deoxyglucose) method, originally presented by A. Gjedde was used for determination of GU. In the cerebral cortex, GU decreased to 70 to 80% at 60 min after i.v. administration of CNZ (0.005-1.0 mg/kg), but CNZ did not change the lumped constant, and this effect was diminished completely by the administration of a BZP antagonist, Ro-15-1788 (5 mg/kg). The maximum effect of CNZ on GU (about 30% decrease) was found at 0.1 mg/kg of CNZ, but increasing the dose to 1 mg/kg had very little additional effect. In vivo BZP-R occupancy was measured using [3H]-Ro-15-1788. Receptor occupancy increased from less than 10% at a dose of 0.005 mg/kg up to essentially 100% at doses of 1 mg/kg or greater. ID50 in dose-response curve of the receptor occupancy for CNZ and ED50 in that of decrease in GU were 0.3 and 0.007 mg/kg, respectively . A nonlinear and hyperbolic relationship was observed between the receptor occupancy and the response for the glucose metabolic rate, indicating that BZP exert the maximum glucose metabolic change at a low fractional receptor occupancy (30-40%).
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Nonlinear relationship between benzodiazepine receptor occupancy and glucose metabolic response in the conscious mouse brain in vivo
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Autor/in / Beteiligte Person: | H, Ishizuka ; Y, Sawada ; K, Ito ; Y, Sugiyama ; H, Suzuki ; T, Iga ; M, Hanano |
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Zeitschrift: | The Journal of pharmacology and experimental therapeutics, Jg. 251 (1989-10-01), Heft 1 |
Veröffentlichung: | 1989 |
Medientyp: | unknown |
ISSN: | 0022-3565 (print) |
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