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  • Strychnine as a potent inhibitor of the brain GABA/benzodiazepine receptor complex
  • Add time:08/17/2019         Source:sciencedirect.com

    The interaction between GABA receptors and benzodiazepine receptors at the molecular level was investigated on rat brain membranes in vitro, using 3H-diazepam binding assays. Stereoselective interaction was confirmed using the two stereoisomers R- and S-trans-4-methyl aminocrotonic acid. This finding further indicates that the GABA receptor recognition site involved in the GABA/benzodiazepine receptor complex is similar to electrophysiologically identified GABA receptors. Strychnine, bicuculline, bicuculline methiodide and THIP antagonized the increase in 3H-diazepam binding induced by muscimol and GABA. Schild analysis indicated that strychnine was a potent competitive inhibitor having a Ki value of 1.9 μM, compared to Ki=0.5 μM for bicuculline, 4.4 μM for bicuculline methiodide, and 7.4 μM for THIP. Strychnine was a more potent inhibitor on hippocampal membranes than on cerebellar membranes. These results indicate that GABA-receptor recognition sites in rat forebrain exhibit some glycine receptor like properties.

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