Canadian journal of anaesthesia = Journal canadien d'anesthésie
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Today's general anesthetics were developed empirically according to their ability to produce memory blockade, analgesia, immobility, and unconsciousness. Thus, a major outstanding question remains: How do anesthetics produce their desirable behavioural end points at the molecular level? Understanding the mechanisms underlying memory blockade is of particular importance, because some patients experience the unexpected recall of events during anesthesia while others experience persistent memory deficits in the postoperative period. This review provides a brief summary of the acute memory-blocking properties of general anesthetics and the neuronal substrates that most likely contribute to memory loss. ⋯ Anesthetics target different receptors and brain regions to modify the various forms of memory. In the hippocampus, extrasynaptic γ-aminobutyric acid subtype A receptors may play a particularly important role. Knowledge regarding the molecular basis of memory blockade may help to address memory disorders associated with the anesthetic state.
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The hippocampal formation occupies a central position for the processing of sensory input into learned, remembered, and consciously retrievable information. The mechanisms by which anesthetic drugs interfere with these processes are now emerging. We review the current understanding of the role of the hippocampal formation in the generation of memory traces and how anesthetics might interfere with its function. ⋯ Anesthesiologists routinely induce the most fascinating pharmacologic effects in existence, the reversible interference of anesthetics with higher cognitive functions. Understanding how the drugs in our custody exert their effects should be our contribution to mankind's universal knowledge base.
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To review the mechanisms of sedative-hypnotic action with respect to the risk of delirium imparted by drugs that act on γ-amino-butyric-acid type A receptors or α(2) adrenoceptors. ⋯ Herein we present our hypothesis that alternate mechanisms of hypnotic action may differentiate the deleriogenic properties of the two classes of sedatives. Future studies should focus on whether a causal relationship can be established between sedative administration, sleep disruption, and delirium.
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The purpose of this review is to summarize current knowledge of detailed biochemical evidence for the role of γ-aminobutyric acid type A receptors (GABA(A)-Rs) in the mechanisms of general anesthesia. ⋯ Establishment of a coherent and consistent structural model of the GABA(A)-R lends support to the conclusion that general anesthetics can modulate function by binding to appropriate domains on the protein. Genetic engineering of mice with mutation in some of these GABA(A)-R residues are insensitive to general anesthetics in vivo, suggesting that further analysis of these domains could lead to development of more potent and specific drugs.