Abstract
Benzodiazepines are thought to exert their pharmacological and clinical effects by interacting with specific receptors on neurones in the central nervous system1–3. Originally, only benzodiazepinoid compounds were known to interact with these receptors, but recently other classes of agents have been discovered which have high affinity for benzodiazepine receptors4. A representative from one of these classes, ethyl β-carboline-3-carboxylate (β-CCE), was obtained from human urine by virtue of its high affinity for benzodiazepine receptors. It was hypothesized that derivatives or congeners of this β-carboline could be related to presumed endogenous ligands, the exact nature of which are unknown3,5. Another ester of β-carboline-3-carboxylic acid, the propyl ester, PrCC, has recently been used as a radioligand for labelling benzodiazepine receptors6: in particular, 3H-PrCC has been observed selectively to label a BZ1 receptor subclass7. Binding of PrCC to benzodiazepine receptors, however, was less enhanced by γ-aminobutyric acid (GABA) than expected6,8. The affinity of benzodiazepines for benzodiazepine receptors is enhanced two to threefold by GABA9–11, probably reflecting the functional coupling of benzodiazepine receptors and GABA receptors at the molecular level. Here we have investigated binding of the methyl ester of β-carboline-3-carboxylic acid (β-CCM), which by itself is a convulsant, in contrast to β-CCE and PrCC. We report that 3H-β-CCM binds to brain benzodiazepine receptors and that, in contrast to binding of 3H-diazepam, 3H-β-CCM binding is reduced by GABA in a bicuculline-sensitive manner.
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Braestrup, C., Nielsen, M. GABA reduces binding of 3H-methyl β-carboline-3-carboxylate to brain benzodiazepine receptors. Nature 294, 472–474 (1981). https://doi.org/10.1038/294472a0
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DOI: https://doi.org/10.1038/294472a0
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