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Enhancement of benzodiazepine binding by progabide (SL 76002) and SL 75102
Author(s) -
Koe B. Kenneth
Publication year - 1983
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430030504
Subject(s) - flunitrazepam , muscimol , chemistry , pharmacology , benzodiazepine , in vivo , diazepam , bicuculline , gabaergic , gabaa receptor , gaba receptor antagonist , flumazenil , biochemistry , receptor , biology , microbiology and biotechnology
The new GABA derivatives, progabide (SL 76002) and SL 75102 (the corresponding carboxylic acid), enhanced [ 3 H]diazepam binding to rat cortical membranes. SL 75102 was as effective as GABA, and both were less active than muscimol. Similar to other GABA agonists, progabide and SL 75102 enhanced binding in vitro by an increase in affinity. The elevation of [ 3 H]diazepam binding in the presence of SL 75102 was antagonized by bicuculline. In ex vivo experiments, brain membrane preparations of mice pretreated with progabide were found to bind a greater amount of [ 3 H]diazepam. This increased binding was characterized by an elevation in B max , while K D was unaffected. [ 3 H]Flunitrazepam binding to brain in vivo was also enhanced in mice pretreated with progabide. Other GABA agonists (muscimol, THIP, isoguvacine) and GABAergic agents (sodium valproate) elicited an increase in [ 3 H]flunitrazepam binding in vivo. Binding of intravenous [ 3 H]flunitrazepam in vivo may be useful for discovering enhancers of benzodiazepine binding.