Binding of [H-3]CB 34, a selective ligand for peripheral benzodiazepine receptors, to rat brain membranes

The 2-phenyl-imidazo[1,2-a]pyridine derivative CB 34 is a ligand for peripheral benzodiazepine receptors. The binding of [H-3]CB 34 to rat cerebrocortical membranes was characterized. Specific binding was rapid, reversible, saturable and of high affinity. Kinetic analysis yielded association and dissociation rate constants of 0.2 x 10(8) M-1 min(-1) and 0.29 min(-1), respectively, Saturation binding experiments revealed a single class of binding sites with a total binding capacity of 188 +/- 8 fmol/mg protein and an apparent dissociation constant of 0.19 +/- 0.02 nM. Specific [H-3]CB 34 binding was inhibited by ligands selective for peripheral benzodiazepine receptors, whereas, with the exception of flunitrazepam and diazepam, ligands for central benzodiazepine receptors were inactive. Of the brain regions examined, the density of the [H-3]CB 34-binding sites was greatest in the hypothalamus and lowest in the cerebral cortex. [H-3]CB 34 is thus a potent and selective ligand for peripheral benzodiazepine receptors and should be proven useful for studies of the roles of these receptors. (C) 2001 Elsevier Science B.V. All rights reserved.