Neuropharmacology
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The metabotropic glutamate receptor 5 (mGluR5) ligands fenobam and AZD9272 have been reported to induce psychosis-like adverse events and to bind at unknown, non-GluR5-related, sites. Based on similarities of the regional binding patterns for [11C]AZD9272 and the monoamine oxidase-B (MAO-B) radioligand [11C]L-deprenyl-D2 in PET studies of the human brain we tested the hypothesis that the unique binding of fenobam and AZD9272 may represent specific binding to the MAO-B. PET data previously acquired for subjects examined using [11C]AZD9272 or [11C]L-deprenyl-D2 were re-evaluated to assess the correlations between radioligand binding parameters in human brain. ⋯ Binding of radiolabeled AZD9272 in vitro was potently inhibited by fenobam or MAO-B compounds, and [11C]L-deprenyl-D2 binding was inhibited by fenobam or AZD9272. The findings are consistent with the hypothesis that both fenobam and AZD9272 bind to the MAO-B, which may be of relevance for understanding the mechanism of the psychosis-like adverse events reported for these compounds. Such understanding may serve as a lead to generate new models for the pathophysiology of psychosis.