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Changes of blood endocannabinoids during anaesthesia: a special case for fatty acid amide hydrolase inhibition by propofol?
Author(s) -
Jarzimski Carina,
Karst Matthias,
Zoerner Alexander A.,
Rakers Christin,
May Marcus,
Suchy Maria T.,
Tsikas Dimitrios,
Krauss Joachim K.,
Scheinichen Dirk,
Jordan Jens,
Engeli Stefan
Publication year - 2012
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2012.04175.x
Subject(s) - fatty acid amide hydrolase , anandamide , propofol , endocannabinoid system , pharmacology , ex vivo , anesthesia , chemistry , sevoflurane , medicine , cannabinoid receptor , biochemistry , antagonist , in vitro , receptor
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Available data from animal studies suggest that the narcotic drug propofol interacts with the endocannabinoid system. Inhibition of enzymatic degradation of anandamide could explain some of the characteristics of propofol. Direct measurements have not been reported yet in humans. WHAT THIS STUDY ADDS • Propofol does not change the time course of anandamide plasma concentrations during anaesthesia. Furthermore, propofol does not inhibit fatty acid amide hydrolase activity ex vivo or in vitro . Thus, specific characteristics of the narcotic drug propofol cannot be explained by peripheral inhibition of anandamide degradation in humans. AIMS The aim of our study was to describe the time course of endocannabinoids during different anaesthesia protocols in more detail, and to challenge the hypothesis that propofol acts as a FAAH inhibitor. METHODS Endocannabinoids were measured during the first hour of anaesthesia in 14 women and 14 men undergoing general anaesthesia with propofol and in 14 women and 14 men receiving thiopental/sevoflurane. We also incubated whole human blood samples ex vivo with propofol and the known FAAH inhibitor oloxa and determined FAAH enzyme kinetics. RESULTS Plasma anandamide decreased similarly with propofol and thiopental/sevoflurane anaesthesia, and reached a nadir after 10 min. Areas under the curve for anandamide (mean and 95% CI) were 53.3 (47.4, 59.2) nmol l −1 60 min with propofol and 48.5 (43.1, 53.8) nmol l −1 60 min with thiopental/sevoflurane ( P = NS). Anandamide and propofol plasma concentrations were not correlated at any time point. Ex vivo FAAH activity was not inhibited by propofol. Enzyme kinetics (mean ± SD) of recombinant human FAAH were K m = 16.9 ± 8.8 µmol l −1 and V max = 44.6 ± 15.8 nmol mg –1 min –1 FAAH without, and K m = 16.6 ± 4.0 µmol l −1 and V max = 44.0 ± 7.6 nmol mg –1 min −1 FAAH with 50 µmol l −1 propofol ( P = NS for both). CONCLUSIONS Our findings challenge the idea that propofol anaesthesia and also propofol addiction are directly mediated by FAAH inhibition, but we cannot exclude other indirect actions on cannabinoid receptors.