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

Abstract:

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 [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). METHODS: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. RESULTS: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. 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.

journal_name

Br J Anaesth

authors

Varnäs K,Finnema SJ,Johnström P,Arakawa R,Halldin C,Eriksson LI,Farde L

doi

10.1016/j.bja.2020.08.052

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

238-244

issue

1

eissn

0007-0912

issn

1471-6771

pii

S0007-0912(20)30756-X

journal_volume

126

pub_type

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