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

Abstract

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 [¹¹C]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 [¹¹C]AZD9272 and of [¹¹C]L-deprenyl-D₂, a radioligand selective for MAO-B in non-human primates (NHPs). Altogether, 12 PET measurements were conducted with a high-resolution research tomograph using the ligands [¹¹C]AZD9272 or [¹¹C]L-deprenyl-D₂ in six cynomolgus monkeys anaesthetised with sevoflurane or ketamine/xylazine. The specific binding of [¹¹C]AZD9272 and [¹¹C]L-deprenyl-D₂ was markedly reduced during anaesthesia with sevoflurane compared with ketamine/xylazine. The reduction was 80-90% (n=3) for [¹¹C]AZD9272 and 77-80% (n=3) for [¹¹C]L-deprenyl-D₂. 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.