Thiopentone and Methohexitone Enantiomers Do Not Act Stereoselectively on the Oxidative Response in Human Neutrophils in vitro

Abstract

To elucidate potential stereoselective effects of single barbiturate isomers, we compared the inhibitory potency of single thiopentone enantiomers, two isomer-enriched mixtures of methohexitone and racemic mixtures of both barbiturates on the fMLP-induced neutrophil oxidative response. A suppression of the response to 50% compared to control required a 100-fold therapeutic concentration of methohexitone, while therapeutic concentrations of the thiopentone racemate led to a significant inhibition (relative fluorescence of neutrophils 0.46 ± 0.03 compared to fMLP controls). The racemate of thiopentone produced significantly greater inhibition than the single enantiomers. Stereoselectivity in favor of one isomer could not be shown for both barbiturates. The greater inhibition by the thiopentone racemate might suggest two separate binding sites for the enantiomers which are positively coupled.

Anaesthetic sensitivity of fMLP-induced cell signalling in Xenopus oocytes

“…The order of potency was found to be methohexitone N propofol N thiopentone (Table 2) whereas in human neutrophils the order of potency against the oxidative response is thiopentone N propofol H methohexitone [18,28]. Although anaesthetics inhibit both fast and slow currents in oocytes, the slow current is consistently more sensitive than the fast current ( Fig.…”

A mini-review of the effects of inhalational and intravenous anesthetics on oxidative stress in dogs

“…Thiopental is a barbiturate which exert antioxidant properties in vitro , either by scavenging ROS ( 48 , 49 ) or by inhibiting the oxidative function of neutrophils ( 50 , 51 ). However, these properties have been shown to be poor compared with propofol in vitro ( 49 , 52 ) and in human ( 53 ) and animal ( 3 , 40 , 54 ) studies.…”

Oxidative stress under general intravenous and inhalation anaesthesia

“…Even though it has largely been replaced by propofol, it is still used for rapid induction of anaesthesia in emergency cases. Research of its antioxidative and immunomodulating properties in human neutrophils showed a significant drop in O 2 - , H 2 O 2 , and OH levels in the presence of clinically relevant thiopental plasma concentrations (30 μg/L) ( 42 ). Thiopental also showed anti-inflammatory properties by significantly reducing chemotaxis and phagocytosis ( 43 ).…”