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Basic Pharmacologic Mechanisms Involved in Benzodiazepine Tolerance and Withdrawal

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Benzodiazepines are widely prescribed for the treatment of anxiety and sleep disorders. Although safe, tolerance develops rapidly to their sedative activity and more slowly to their anticonvulsant activity. In animals anxiolytic tolerance has also been measured. Abrupt cessation of benzodiazepine treatment leads to symptoms of withdrawal. The mechanisms responsible for these phenomena are not known. Benzodiazepines act via GABAA receptors, but do not appear to produce tolerance and dependence by simple downregulation of receptor number. GABAA receptors are hetero-oligomers comprised of multiple subunits encoded by a multigene family. The molecular effects of long-term benzodiazepine exposure are reviewed and a model is presented that draws on results from a number of research groups working in this area.
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Keywords: Benzodiazepine

Document Type: Review Article

Publication date: 01 January 2002

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  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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