Effects of sevoflurane anaesthesia on radioligand binding to monoamine oxidase-B in vivo

BACKGROUND: The molecular actions underlying the clinical effects of inhaled anaesthetics such as sevoflurane and isoflurane are not fully understood. Unexpected observations in positron emission tomography (PET) studies with [(11)C]AZD9272, a metabotropic glutamate receptor 5 (mGluR5) radioligand with possible affinity for monoamine oxidase-B (MAO-B), suggest that its binding is sensitive to anaesthesia with sevoflurane. The objective of the present study was to assess the effects of sevoflurane anaesthesia on the binding of [(11)C]AZD9272 and of [(11)C]L-deprenyl-D(2), a radioligand selective for MAO-B in non-human primates (NHPs). METHODS: Altogether, 12 PET measurements were conducted with a high-resolution research tomograph using the ligands [(11)C]AZD9272 or [(11)C]L-deprenyl-D(2) in six cynomolgus monkeys anaesthetised with sevoflurane or ketamine/xylazine. RESULTS: The specific binding of [(11)C]AZD9272 and [(11)C]L-deprenyl-D(2) was markedly reduced during anaesthesia with sevoflurane compared with ketamine/xylazine. The reduction was 80–90% (n=3) for [(11)C]AZD9272 and 77–80% (n=3) for [(11)C]L-deprenyl-D(2). CONCLUSIONS: Sevoflurane anaesthesia inhibited radioligand binding to MAO-B in the primate brain. The observation of lower MAO-B binding at clinically relevant concentrations of sevoflurane warrants further exploration of the potential role of MAO-B related mechanisms in regulation of systemic blood pressure during anaesthesia.