An in vitro binding assay which differentiates benzodiazepine ‘agonists’ and ‘antagonists’

Abstract An in vitro test which discriminates benzodiazepine ‘agonists’ and ‘antagonists’ has been developed by exploiting the apparent differences in modulation of the benzodiazepine receptor by these classes of compounds. In the presence of 10 μM GABA, the potency of benzodiazepine ‘agonists’ (i.e., compounds which bind to the benzodiazepine receptor with a relatively high affinity and share pharmacologic properties with benzodiazepines) to displace [ 3 H]3-carboethoxy-β-carboline is significantly increased. In contrast, the potency of benzodiazepine ‘antagonists’ (compounds which have been demonstrated to antagonize some of the pharmacologic actions of benzodiazepines) is not altered by GABA. Several chemically diverse classes of compound have been examined in this test, and within the limited number of compounds examined, this test accurately predicts ‘agonist’ and ‘antagonist’ actions in vivo.