Anxiogenic and non-anxiogenic benzodiazepine antagonists (original) (raw)

Nature volume 301, pages 64–66 (1983)Cite this article

Abstract

Benzodiazepines are widely used anxiolytic and anticonvulsant drugs, and brain receptors for these drugs have been characterized by Möhler and Okada1 and Squires and Braestrup2. Recently, substances that antagonize benzodiazepine binding to brain receptors have been discovered3,4. These benzodiazepine antagonists were shown to block the central effects of benzodiazepines and particularly their anticonvulsive properties3,5,6. Two such antagonists, Ro 15-1788 (an imidazodiazepine) and methyl _β_-carboline-3-carboxylate (_β_-CCM), have recently been shown to have different intrinsic pharmacological properties. β;-CCM, injected into baboons, cats, mice and rats, is a convulsant6–8, whereas Ro 15-1788 lacks such an activity. Thus, the separation of convulsant and non-convulsant antagonists has been proposed8. We suggest here that a sub-classification of antagonists is also valid at the behavioural level, based on a conflict model in mice. We show that Ro 15-1788 and _β_-CCM antagonize the anxiolytic effect of benzodiazepines. In addition, we find that, when injected alone, Ro 15-1788 has no anxiogenic effects while _β_-CCM has anxiogenic properties. We therefore propose that _β_-CCM is an anxiogenic convulsant benzodiazepine antagonist and that Ro 15-1788 is a non-anxiogenic non-convulsant benzodiazepine antagonist.

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Authors and Affiliations

  1. Laboratoire de Physiologie Nerveuse, Centre National de la Recherche Scientifique, 91190, Gif-sur-Yvette, France
    Lia Prado de Carvalho, Gisela Grecksch, Georges Chapouthier & Jean Rossier

Authors

  1. Lia Prado de Carvalho
  2. Gisela Grecksch
  3. Georges Chapouthier
  4. Jean Rossier

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de Carvalho, L., Grecksch, G., Chapouthier, G. et al. Anxiogenic and non-anxiogenic benzodiazepine antagonists.Nature 301, 64–66 (1983). https://doi.org/10.1038/301064a0

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