Repeated administration of diazepam reduces [3H]Ro 5-4864 binding in cerebral cortex of rats.
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.
Diana
G
G
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Massotti
M
M
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; C028513:4'-chlorodiazepam; D002998:Clonazepam; D003975:Diazepam