2 resultados para OPIOID

em Brock University, Canada


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The prescription of opioid analgesics has risen sharply in North America over the past two decades. This increase has been accompanied by a rise in overdoses. The present study draws on administrative data collected from emergency department contacts to describe the epidemiology of opioid overdose in Ontario b~tween 2002 and 2006 and to examine the role of regional variation in availability of specialist care. The number of poisonings increased from 1250 (10.9 per 100,000) in FY2002 to 1816 (15.2 per 100,000) in FY2005. Local concentration of specialist physicians was significantly associated with the incidence of opioid overdose, inversely at most levels of availability, but positively at very high levels. Regional variation in incidence was also associated with demographics, median family income, and the rate of other drug poisonings. Policy options for limiting opioid-related harms are limited, but improvements in monitoring and clinical management may prove valuable.

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The opioid receptors consist of three main subtypes; μ, δ, and κ. Previous binding studies have shown that fragments of the milk protein, β-casein, known as β-casomorphins are agonists of these receptors which are selective for the μ receptor subtype. Using the crystal structures of these three receptors, computational molecular docking studies were done using the software GOLD to determine the conformation of β-casomorphin-5 and 7 when they bind to these three opioid receptors. GOLD was able to discriminate among the three receptors when docking the rigid ligands co-crystalized with the receptors. However, GOLD could not discriminate among the three receptors for either of the highly flexible β-casomorphins. A per amino acid scoring method was developed to overcome this problem. This method was used to predict the conformation of both β-casomorphin-5 and 7 in the μ receptor and determine that the two amino acid residues, Lys303 and Trp318 of the μ receptor are responsible for discriminating among the three receptor subtypes for binding of the β-casomorphin-5 and 7.