Specific binding of 35S-t-butylbicyclophosphorothionate (TBPS) was studied in synaptosomal membranes of rat cerebral cortex under nonequilibrium conditions. TBPS binding proved to be suitable for the characterization of not only the efficacy but also the potency of benzodiazepine (BZ) receptor ligands in vitro. Five BZ agonists accelerated the kinetics of TBPS binding in a concentration-dependent manner. The ec50 values of acceleration correlated with displacing potencies at BZ receptors suggesting the involvement of high affinity central BZ binding sites. The binding enhancement by 0.3 m̊M oxazepam could be antagonized in vitro by Ro-15-1788 (ic50 = 43 nM) and by oxazepam α,α-Me2-β-phenylpropionate ester (ic50 = 2-3 m ̊M), a weak BZ antagonist. Antagonism might be attributed to the acyl moiety since a 3-O-ether derivative appeared to be a partial agonist. Structural requirements of the conversion of BZs from agonists into antagonists are discussed.
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