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  • Title: Repeated administration of diazepam reduces [3H]Ro 5-4864 binding in cerebral cortex of rats.
    Author: Diana G, Massotti M.
    Journal: Pharmacol Biochem Behav; 1992 Jun; 42(2):297-300. PubMed ID: 1631183.
    Abstract:
    Binding of [3H]Ro 5-4864 to mitochondrial membrane preparations of rat cerebral cortex was measured after repeated (5 days) IV administration of diazepam (10 mg/kg daily) and clonazepam (2.5 mg/kg daily). The B(max) value for [3H]Ro 5-4864 was significantly reduced in rats treated with diazepam (-49%) but not in those treated with clonazepam. These findings suggest the involvement of peripheral-type binding sites in the development of rapid tolerance to the sedative effects of benzodiazepines. A downregulation of [3H]Ro 5-4864 (-65%) was also observed after repeated administration of Ro 5-4864 (4 mg/kg daily), thus confirming that this compound behaves as an agonist at its own recognition sites.
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