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Radioreceptor assay of benzodiazepines in cerebrospinal fluid during chronic flurazepam treatment in cats


European Journal of Pharmacology 105(3-4): 301-308
Radioreceptor assay of benzodiazepines in cerebrospinal fluid during chronic flurazepam treatment in cats
A radioreceptor assay was used to measure benzodiazepine-like activity in CSF of cats during chronic flurazepam treatment. Benzodiazepine-like activity was measured by the displacement of [3H]flunitrazepam from benzodiazepine receptors in homogenates of rat cerebral cortex. Cats were given 5 mg/kg flurazepam daily, and tolerance was measured by rating several indicators of neurological impairment. CSF was sampled 1 h after flurazepam administration, when drug actions were greatest. Ataxia and muscle relaxation were greatest on the first treatment day, then decreased despite increasing CSF benzodiazepine-like activity. By day 11, CSF activity was 3 times that measured 1 h after the first chronic dose. CSF benzodiazepine-like activity declined slowly after treatment and approached zero by the 10th day after treatment. This residual activity, probably due to active flurazepam metabolites, correlates with the observation that physical dependence is present in these cats up to 7 days after the end of chronic treatment. The rapid loss of drug effect despite increasing active drug levels shows that the nervous system is capable of a rapid and profound adaptation to the presence of benzodiazepines.

Accession: 006255023

PMID: 6510471

DOI: 10.1016/0014-2999(84)90622-8

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