STUDIES ON THE BINDING OF [H-3] FLUMAZENIL AND [H-3] SARMAZENIL IN POSTMORTEM HUMAN BRAIN

Two benzodiazepine analogues, [H-3]flumazenil and [H-3]sarmazenil, were used to study the GABA(A)/benzodiazepine receptor complex in human post-mortem brain using in vitro receptor assays on homogenates and whole hemisphere autoradiography. Both radioligands bound in a saturable manner to single binding sites in the tissue preparations from any brain region. The highest levels of binding were found in the cortical regions and in cortex cerebelli. Both [H-3]flumazenil and [H-3]sarmazenil were excellent radioligands for autoradiography with high binding in cerebral and cerebellar cortex with no or very low binding in areas with white matter. The addition of a high concentration of flumazenil or clonazepam did not inhibit the binding of [H-3]sarmazenil to granule cells in the cerebellum while the binding of [H-3]flumazenil was abolished completely in all regions. The results show that with the two different radioligands, one an antagonist and one a partial inverse agonist, the binding pattern to GABA(A)/benzodiazepine receptor complex is approximately similar in most brain regions. The additional binding seen in the cerebellum with [H-3]sarmazenil is suggested to be due to binding to an alpha6-containing complex.