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β‐Lumicolchicine Interacts with the Benzodiazepine Binding Site to Potentiate GABA A Receptor‐Mediated Currents
Author(s) -
Mihic S. John,
Whatley Valerie J.,
McQuilkin Susan J.,
Harris R. Adron
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62051790.x
Subject(s) - gabaa receptor , flumazenil , flunitrazepam , receptor , chemistry , biophysics , muscimol , pharmacology , benzodiazepine , antagonist , gaba receptor antagonist , biology , biochemistry , bicuculline
An analogue of colchicine,β‐lumicolchicine, does not bind tubulin or disrupt microtubules. However, this compound is not pharmacologically completely inactive. β‐Lumicolchicine was found to competitively inhibit [ 3 H]flunitrazepam binding and to enhance muscimol‐stimulated 36 Cr‐uptake in mouse cerebral cortical microsacs. It also markedly potentiated GABA responses in Xenopus oocytes expressing human α 1 β 2 γ 2S , but not α 1 β 2 , GABA A receptor subunits; this potentiation was reversed by the benzodiazepine receptor antagonist flumazenil. These results strongly suggest a direct effect of β‐Lumicolchicine on the GABA A receptor/chloride channel complex and caution that it possesses pharmacological effects, despite its inability to disrupt microtubules. Furthermore, β‐Lumicolchicine is structurally unrelated to benzodiazepines or quinolines and may provide a novel approach to the synthesis of ligands for this receptor.