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Anxiogenic and non-anxiogenic benzodiazepine antagonists

Nature volume 301, pages 6466 (06 January 1983) | Download Citation

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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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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

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https://doi.org/10.1038/301064a0

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