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  • Title: Long-term exposure of cortical cell cultures to clonazepam reduces benzodiazepine receptor binding.
    Author: Sher PK.
    Journal: Exp Neurol; 1986 May; 92(2):360-8. PubMed ID: 3007195.
    Abstract:
    To determine if reduced drug efficacy after long-term exposure to clonazepam may be a consequence of benzodiazepine receptor alterations, cerebral cortical cell cultures were exposed to the drug (200 nM) for 14 days. Receptor binding was assayed on living cells in situ. After drug exposure, binding in experimental cultures differed markedly from controls with respect to total, specific, and clonazepam-displaceable (neuronal) benzodiazepine binding (60%, 53%, and 6% of control values, respectively) but recovered within 96 h of drug removal. RO5-4864-displaceable (nonneuronal) binding was modestly reduced at 0 time (72% of control), but returned to control values in 24 h. The differences in binding could be attributable to a relatively reduced affinity of the high-affinity binding site (Kd approximately 18 nM for controls and approximately 30 nM for drug-exposed cultures) but not to changes in the low-affinity binding site or to reduced numbers of receptors.
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