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General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
  • N. Franks
  • Psychology, Medicine
  • Nature Reviews Neuroscience
  • 1 May 2008
Comparisons with the features of natural sleep are helping to understand how anaesthetics work and the neuronal pathways that they affect, and suggests that the thalamus and the neurons that regulate its activity are the key to understanding how anaesthetic-induced loss of consciousness is understood. Expand
Molecular and cellular mechanisms of general anaesthesia
It is now clear that anaesthetics act directly on proteins rather than on lipids, with potentiation of postsynaptic inhibitory channel activity best fitting the pharmacological profile observed in general anaesthesia. Expand
Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites
The crystal structure of HSA complexed with five molecules of myristate at 2.5 Å resolution is determined and it is shown that fatty acid molecules bind in long, hydrophobic pockets capped by polar side chains, many of which are basic. Expand
The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway
It is concluded that the tuberomammillary nucleus (TMN) is a discrete neural locus that has a key role in the sedative response to GABAergic anesthetics. Expand
Crystal structure of firefly luciferase throws light on a superfamily of adenylate-forming enzymes.
Firefly luciferase is the first member of a superfamily of homologous enzymes, which includes acyl-coenzyme A ligases and peptide synthetases, to have its structure characterized. Expand
Temperature Dependence of the Potency of Volatile General Anesthetics: Implications for In Vitro Experiments
The aqueous‐phase (but not the gas‐phase) minimum alveolar concentration calculated at normal body temperature is, to a first approximation, the appropriate choice for a clinically relevant anesthetic concentration. Expand
The &agr;2-Adrenoceptor Agonist Dexmedetomidine Converges on an Endogenous Sleep-promoting Pathway to Exert Its Sedative Effects
It is proposed that endogenous sleep pathways are causally involved in dexmedetomidine-induced sedation; dexmedETomidine's sedative mechanism involves inhibition of the LC, which disinhibits VLPO firing. Expand
Mechanisms of general anesthesia.
Overall, the data can be explained by supposing that the primary target sites underlying general anesthesia are amphiphilic pockets of circumscribed dimensions on particularly sensitive proteins in the central nervous system. Expand
A propofol binding site on mammalian GABAA receptors identified by photolabeling
A novel propofol analogue photolabeling reagent is synthesized that has a biological activity very similar to that of Propofol, and it is confirmed that this reagent labeled known prop ofol binding sites in human serum albumin which have been identified using X-ray crystallography. Expand