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Partial agonists for brain GABA/benzodiazepine receptor complex

Nature volume 280, pages 331–333 (1979)Cite this article

Abstract

BENZODIAZEPINE receptors in the brain1 are activated by γ-aminobutyric acid (GABA) and by the GABA agonist muscimol in vitro2. This activation may be related to the GABA-potentiating effects of benzodiazepines observed in electro-physiological studies (see ref. 3 for review). The enhancement of specific 3H-diazepam binding by GABA agonists is inhibited by bicuculline and thus offers a unique high-affinity binding system for investigations in vitro of agonist–antagonist interactions at GABA receptors in the central nervous system. We report here that two GABA-mimetic compounds, 3-aminopropane-sulphonic acid (APS) and isoguvacine, are partial agonists (mixed agonists/antagonists) with intermediate efficacies. Imidazoleacetic acid (IAA) is also a partial agonist but with only marginal agonist activity, and the new GABA-mimetics piperidine-4-sulphonic acid (PSA) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol (THIP) are competitive antagonists to the GABA/benzodiazepine receptor complex.

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Authors and Affiliations

  1. A/S Ferrosan, Psychopharmacological Research Laboratory, Sydmarken 1–5, DK-2860, Soeborg, Denmark

    CLAUS BRAESTRUP

  2. Sct. Hans Mental Hospital, 4000, Roskilde, Denmark

    MOGENS NIELSEN

  3. Royal Danish School of Pharmacy, Universitetsparken, DK-2100, Copenhagen, Denmark

    P. KROGSGAARD-LARSEN & ERIK FALCH

Authors
  1. CLAUS BRAESTRUP
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  2. MOGENS NIELSEN
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  3. P. KROGSGAARD-LARSEN
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  4. ERIK FALCH
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BRAESTRUP, C., NIELSEN, M., KROGSGAARD-LARSEN, P. et al. Partial agonists for brain GABA/benzodiazepine receptor complex. Nature 280, 331–333 (1979). https://doi.org/10.1038/280331a0

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