Stereoselective inhibition of the binding of ( super(3)H)PK 11195 to peripheral-type benzodiazepine binding sites by a quinoline-propanamide derivative

The specific binding of ( super(3)H)PK 11195 to the peripheral-type benzodiazepine binding site is inhibited by the 1-enantiomer of N,N-diethyl- alpha -methyl-2-phenyl-4-quinoline-propanamide ((-)Q sub(1)) but not by its d-enantiomer ((+)Q sub(1)). (-)Q sub(1) inhibited ( super(3)H)PK 11195 binding to several rat tissues with an IC sub(50) of less than 10 nM whereas (+)Q sub(1) was at least 500 times less potent. This stereoselectivity was observed in all the tissues tested. The same stereoselectivity was found for the displacement of the binding of ( super(3)H)PK 11195 in vivo. Neither isomer had appreciable affinity for central-type benzodiazepine binding sites (( super(3)H)diazepam) nor for voltage-sensitive calcium channels.