Abstract
The effects of the benzodiazepine receptor antagonist XR 93 426, a β-carboline, on local cerebral glucose utilization (LCGU) was examined by using quantitative in-vivo autoradiography with [ 3H]2-deoxyglucose. ZK 93 426 was found to increase local cerebral glucose utilization primarily in prefrontal, cingulate, olfactory and visual cortical regions, as well as the claustrum, nucleus accumbens, anteroventral thalamus, substantia nigra, and dorsal raphe nucleus. This pattern of changes of LCGU produced by ZK 93 426 seems to represent neither a mirror image of the metabolic effects of benzodiazepine receptor agonists nor the pattern of effects on LCGU induced by the partial inverse agonist β-carboline FG 7142. The unique pattern of regional changes of glucose utilization induced by ZK 93 426 are discussed with respect to recent findings on its promnestic and antiamnestic properties in animals and humans. It is concluded that ZK 93 426 does not seem to fit into the conventional classification scheme of benzidiazepine receptor ligands; thus, the term ‘selective inverse agonist’ is proposed.
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