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1 The pharmacological properties of a benzodiazepine receptor (BZR) partial agonist, Y‐23684 were investigated in comparison with those of diazepam, a conventional BZR full agonist. 2 Y‐23684 and diazepam showed high and selective affinity for the BZR with Ki values of 41 and 5.8 nm, respectively. 3 In contrast to diazepam, variability was noted in the anticonvulsive potency of Y‐23684 depending on convulsants (bicuculline, pentylenetetrazol and maximal electrical shock). Y‐23684 produced the most potent protective effect against bicuculline in rats and mice with ED50s of 1.3 and 1.2 mg kg−1, respectively. 4 In rat conflict models (Geller‐Seifter and water‐lick tests), Y‐23684 produced an antipunishment action at doses 2–4 times lower than diazepam. In contrast to diazepam, Y‐23684 did not affect unpunished responding up to 50 mg kg−1in the Geller‐Seifter test. 5 In other rat models of anxiety (social interaction and elevated plus‐maze tests), Y‐23684 was as efficacious as and ten fold more potent than diazepam. In a mouse model of anxiety (exploration (light/dark box) test), Y‐23684 was as efficacious and two fold less potent as diazepam. In these paradigms, Y‐23684 showed a selective anxiolytic profile over a wide dose‐range without loss of efficacy and sedative action. 6 The impairment of motor coordination (rotarod) and potentiation of CNS depressants (ethanol and hexobarbitone) by Y‐23684 was much weaker than that of diazepam. 7 These results suggest that Y‐23684 would be a potent and selective anxiolytic agent in man with less side‐effects than conventional BZ‐anxiolytics.
British Journal of Pharmacology – Wiley
Published: Apr 1, 1994
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