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10.1097/ALN.0b013e31825685a6 http://scihub22266oqcxt.onion/10.1097/ALN.0b013e31825685a6 C4056591!4056591!22531340     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=22531340&cmd=llinks): Failed to open stream: HTTP request failed! 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AZD-3043: A Novel, Metabolically-Labile Sedative/Hypnotic Agent with Rapid and Predictable Emergence from Hypnosis |pdf=|usr=}}{{22531340}} gab.com Text AZD-3043: A Novel, Metabolically-Labile Sedative/Hypnotic Agent with Rapid and Predictable Emergence from Hypnosis JO: Anesthesiology http://www.kidney.de/pget.php?&tw=1&pmid=22531340 #FOAvip Background: Propofol can be associated with delayed awakening after prolonged infusion. The aim of this study was to characterize the preclinical pharmacology of AZD-3043, a positive allosteric modulator of the ?-aminobutyric acidA (GABAA) receptor containing a metabolically-labile ester moiety. We postulated that its metabolic pathway would result in a short acting clinical profile. Methods: The effects of AZD-3043, propofol and propanidid were studied on GABAA receptor-mediated chloride currents in embryonic rat cortical neurons. Radioligand binding studies were also performed. The in vitro stability of AZD-3043 in whole blood and liver microsomes was evaluated. The duration of the loss of righting reflex and effects on the electroencephalograph evoked by bolus or infusion intravenous (IV) administration were assessed in rats. A mixed-effects kinetic-dynamic model using minipigs permitted exploration of the clinical pharmacology of AZD-3043. Results: AZD-3043 potentiated GABAA receptor-mediated chloride currents and inhibited [35S]tert-butylbicyclophosphorothionate binding to GABAA receptors. AZD-3043 was rapidly hydrolyzed in liver microsomes from humans and animals. AZD-3043 produced hypnosis and electroencephalograph depression in rats. Compared to propofol, AZD-3043 was shorter acting in rats and pigs. Computer simulation using the porcine kinetic-dynamic model demonstrated that AZD-3043 has very short 50 and 80% decrement times independent of infusion duration. Conclusions: AZD-3043 is a positive allosteric modulator of the GABAA receptor in vitro and a sedative/hypnotic agent in vivo. The esterase dependent metabolic pathway results in rapid clearance and short duration of action even for long infusions. AZD-3043 may have clinical potential as a sedative/hypnotic agent with rapid and predictable recovery. Twit Text FOAVip AZD-3043: A Novel, Metabolically-Labile Sedative/Hypnotic Agent with Rapid and Predictable Emergence from Hypnosis ????Anesthesiology http://www.kidney.de/pget.php?&tw=1&pmid=22531340 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=22531340 #FOAvip English Wikipedia <ref>{{Cite pmid|22531340}}</ref> AZD-3043: A Novel, Metabolically-Labile Sedative/Hypnotic Agent with Rapid and Predictable Emergence from Hypnosis #MMPMID22531340 Egan TD; Obara S; Jenkins TE; Jaw-Tsai SS; Amagasu S; Cook DR; Steffensen SC; Beattie DT Anesthesiology 2012[Jun]; 116 (6): 1267-77 PMID22531340show ga Background: Propofol can be associated with delayed awakening after prolonged infusion. The aim of this study was to characterize the preclinical pharmacology of AZD-3043, a positive allosteric modulator of the ?-aminobutyric acidA (GABAA) receptor containing a metabolically-labile ester moiety. We postulated that its metabolic pathway would result in a short acting clinical profile. Methods: The effects of AZD-3043, propofol and propanidid were studied on GABAA receptor-mediated chloride currents in embryonic rat cortical neurons. Radioligand binding studies were also performed. The in vitro stability of AZD-3043 in whole blood and liver microsomes was evaluated. The duration of the loss of righting reflex and effects on the electroencephalograph evoked by bolus or infusion intravenous (IV) administration were assessed in rats. A mixed-effects kinetic-dynamic model using minipigs permitted exploration of the clinical pharmacology of AZD-3043. Results: AZD-3043 potentiated GABAA receptor-mediated chloride currents and inhibited [35S]tert-butylbicyclophosphorothionate binding to GABAA receptors. AZD-3043 was rapidly hydrolyzed in liver microsomes from humans and animals. AZD-3043 produced hypnosis and electroencephalograph depression in rats. Compared to propofol, AZD-3043 was shorter acting in rats and pigs. Computer simulation using the porcine kinetic-dynamic model demonstrated that AZD-3043 has very short 50 and 80% decrement times independent of infusion duration. Conclusions: AZD-3043 is a positive allosteric modulator of the GABAA receptor in vitro and a sedative/hypnotic agent in vivo. The esterase dependent metabolic pathway results in rapid clearance and short duration of action even for long infusions. AZD-3043 may have clinical potential as a sedative/hypnotic agent with rapid and predictable recovery. äAZD-3043: A Novel, Metabolically-Labile Sedative/Hypnotic Agent with R(epmc).pdf DeepDyve Pubget Overpricing