Letter | Published:

Ethyl β-carboline-3-carboxylate shows differential benzodiazepine receptor interaction

Nature volume 286, pages 606607 (07 August 1980) | Download Citation

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Abstract

High-affinity binding of 3H-diazepam and 3H-flunitrazepam has provided evidence for the presence of benzodiazepine receptors on brain neurones1–6. Pharmacological evidence showing a clear correlation between receptor affinity and in vivo pharmacological potency for several benzodiazepines7 and a link between benzodiazepine receptors and GABA (γ-aminobutyric acid) receptors at the molecular level8,9, indicates that these receptors are relevant to the pharmacological and clinical effects of benzodiazepines. In searching for possible endogeneous ligands for benzodiazepine receptors we have recently isolated ethyl β-carboline-3-carboxylate (β-CCE) from human urine and brain, and shown that β-CCE has a higher affinity than diazepam for brain benzodiazepine receptors10. β-CCE itself is probably not present in the brain, but may be closely related to an endogenous benzodiazepine receptor ligand10. We report here that β-CCE, in contrast to benzodiazepines, can distinguish clearly between benzodiazepine receptors in cerebellum and hippocampus. This result strongly indicates that benzodiazepine receptors are not a single class of non-interacting entities. It has not been possible to determine whether two distinct receptors are present and/or whether true negative cooperativity exists among hippocampal, but not cerebellar, benzodiazepine receptors.

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Author information

Author notes

    • Claus Bræstrup

    Research Laboratories, A/S Ferrosan, Sydmarken 1-5, DK 2860 Soeborg, Denmark

Affiliations

  1. Psychopharmacological Research Laboratory, St Hans Mental Hospital, Department E, DK-4000 Roskilde, Denmark

    • Mogens Nielsen
    •  & Claus Bræstrup

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DOI

https://doi.org/10.1038/286606a0

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