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Biochemical evidence for a new benzodiazepine receptor antagonist
Author(s) -
Kenneth Koe B.,
Kondratas Elena,
Lebel Lorraine A.,
Minor Katherine W.
Publication year - 1985
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.430060410
Subject(s) - inverse agonist , antagonist , flunitrazepam , neurochemical , benzodiazepine , chemistry , gabaa receptor , pharmacology , flumazenil , diazepam , agonist , receptor , competitive antagonist , endocrinology , medicine , biochemistry , biology
1‐(3‐Chlorophenyl)‐3‐diethylcarbamoyl‐1 H‐1,2,4‐triazole (CP‐32,961) inhibited [ 3 H]diazepam binding to rat cortical membrances and [ 3 H]flunitrazepam binding to mouse brain in vivo. Its inhibition of the binding of [ 3 H]Ro 15‐1788 (benzodiazepine receptor antagonist) to these membranes was not facilitated by added GABA; CP‐32,961 exhibited a GABA ratio of 0.84 compared to 2.44 for diazepam. Cerebellar cyclic GMP content in rats was raised by CP‐32,961, which also further elevated the increased cyclic GMP levels induced by isoniazid. These neurochemical actions are similar to those shown by ethyl β‐carboline‐3‐carboxylate (β‐CCE) and suggest that CP‐32,961 is a benzodiazepine receptor antagonist with inverse agonist activity.