Anesthesiology
-
WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Structure-activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by L-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. ⋯ CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by L-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.
-
WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: The mechanism by which anesthetics induce a loss of consciousness remains a puzzling problem. We hypothesized that a cortical signature of anesthesia could be found in an increase in similarity between the matrix of resting-state functional correlations and the anatomical connectivity matrix of the brain, resulting in an increased function-structure similarity. ⋯ Whatever the molecular mechanism, anesthesia led to a massive reconfiguration of the repertoire of functional brain states that became predominantly shaped by brain anatomy (high function-structure similarity), giving rise to a well-defined cortical signature of anesthesia-induced loss of consciousness.
-
WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Naphthalene-etomidate, an etomidate analog containing a bulky phenyl ring substituent group, possesses very low γ-aminobutyric acid type A (GABAA) receptor efficacy and acts as an anesthetic-selective competitive antagonist. Using etomidate analogs containing phenyl ring substituents groups that range in volume, we tested the hypothesis that this unusual pharmacology is caused by steric hindrance that reduces binding to the receptor's open state. ⋯ Steric hindrance selectively reduces phenyl ring-substituted etomidate analog binding affinity to the two β - α anesthetic binding sites on the GABAA receptor's open state, suggesting that the binding pocket where etomidate's phenyl ring lies becomes smaller as the receptor isomerizes from closed to open.