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Current Topics in Pharmacology   Volumes    Volume 9  Issue 1
Propofol pharmacology and interactions with issues
Alexandra Acco, Adelar Bracht
Pages: 33 - 45
Number of pages: 13
Current Topics in Pharmacology
Volume 9  Issue 1

Copyright © 2005 Research Trends. All rights reserved


Propofol (2,6-diisopropylphenol) is an intravenous anaesthetic used for general anaesthesia or as a sedative during surgeries and intense care. Due to the short duration of its anaesthetic effects propofol is also utilized for anaesthesia maintenance in association with narcotics, benzodiazepine derivatives and inhalatory agents. Propofol induces central depression by means of a potent agonistic effect on the GABA ergic transmission, mediated by binding to the GABAA receptor, and by reducing the metabolic activity in the brain. There is evidence that propofol also exerts a presynaptic action, leading to an accumulation of γ-aminobutyric acid (GABA) in the synaptic cleft and contributing to its hyperpolarizing action in postsynaptic receptors, which are coupled to chlorine channels. Propofol is rapidly metabolized in the liver and other tissues. The hepatic metabolism of propofol is ten times faster than that of thiopental. The pharmacokinetic behaviour of propofol presents several complexities. Analysis of the various blood concentration versus time curves that were obtained until now did not allow a definitive conclusion about the model that describes the behaviour of propofol, but generally a two- compartment model has been assumed to be valid. Propofol permeates the cell membrane at very high rates and has a very high affinity for tissues so that its apparent volume of distribution, depending on the conditions and kind of tissue, can exceed several fold the aqueous space. Since it interacts intensily with membranes and proteins the drug also exerts many metabolic effects, including impairment of energy metabolism. The study of interactions of propofol with tissues, especially those ones occurring at the interface between membranes and proteins is likely to reveal new details about the general mode of action of the drug as well as about the mechanism of its anaesthetic action.    

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