Agonist and antagonist benzodiazepine receptor interaction in vitro

ABSTRACT A representative of a novel series of imidazodiazepines, Ro 15-1788, selectively antagonizes all major central actions of benzodiazepines by competitive, high-affinity interactions

with benzodiazepine receptors (BR) in the central nervous system (CNS)1–3. Doses of Ro 15-1788 sufficient to antagonize benzodiazepine actions have been shown _per se_ to lack phamacological

action in animals and man1–4. Thus Ro 15-1788 provides a highly selective tool for experimental investigations of BR-mediated events and is of therapeutic value in all cases where a rapid

termination of benzodiazepine actions is indicated. Using 3H-labelled Ro 15–1788 as radioligand in equilibrium binding studies _in vitro_, we show here that 3H-Ro 15-1788 interacts with the

same number of BR sites as the agonist 3H-clonazepam in various brain regions. However, their mode of receptor interaction is different. In conditions which alter receptor affinity for

3H-clonazepam binding, such as addition of γ-aminobutyric acid (GABA) or certain ions, no change is seen in 3H-Ro 15-1788 binding. This effect can be used to distinguish between

benzodiazepine receptor agonists and antagonists _in vitro_. Furthermore, the thermodynamics of agonist and antagonist receptor interaction are different, but only at temperatures above 21

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Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd, CH-4002, Basle, Switzerland H. Möhler & J. G. Richards Authors * H. Möhler View author publications You can also

search for this author inPubMed Google Scholar * J. G. Richards View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Möhler, H., Richards, J. Agonist and antagonist benzodiazepine receptor interaction _in vitro_. _Nature_ 294, 763–765 (1981).

https://doi.org/10.1038/294763a0 Download citation * Received: 13 August 1981 * Accepted: 28 October 1981 * Issue Date: 24 December 1981 * DOI: https://doi.org/10.1038/294763a0 SHARE THIS

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