A comparison of Ro 16-6028 with benzodiazepine receptor 'full agonists' on GABAA receptor function

Deborah A. Finn, Kelvin W. Gee

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Ro 16-6028 (bretazenil) has a pharmacological profile characteristic of a partial agonist at the γ-aminobutyric acidA (GABAA) receptor-linked benzodiazepine site. The present study utilized modulation of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding and enhancement of GABA-stimulated 36Cl- uptake to further assess Ro 16-6028's partial agonist profile in vitro. Ro 16-6028 was the most potent benzodiazepine examined, exhibiting an IC50 (concentration at which half-maximal inhibition of specific [35S]TBPS binding occurs) of 6.1 nM, compared to clonazepam (7.9 nM), flunitrazepam (13.6 nM) and diazepam (91.1 nM). The rank order of potency for inhibition of [35S]TBPS binding was identical to that for inhibition of [3H]flunitrazepam binding. However, Ro 16-6028 was less efficacious in that it produced 27% inhibition of specific [35S]TBPS binding, compared to clonazepam (34%), flunitrazepam (41%) or diazepam (49%antagonized the inhibition of [35]TBPS binding produced by 10 μM, diazepam. Ro 16-6028 was also more potent and less efficacious than diazepam in potentiating GABA-stimulated 36Cl- uptake. These results provide further evidence that Ro 16-6028 is acting as a partial agonist at the benzodiazepine receptor in modulating function of the GABAA receptor complex.

Original languageEnglish (US)
Pages (from-to)233-237
Number of pages5
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume247
Issue number3
DOIs
StatePublished - Nov 15 1993

Keywords

  • Benzodiazepine
  • Cl uptake
  • GABA receptor complex
  • TBPS (t-butylbicyclophosphorothionate) binding

ASJC Scopus subject areas

  • Pharmacology

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