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Propranolol is a beta-adrenergic receptor blocking agent (Long) and has been used to treat amongst many other things, high blood pressure, glaucoma, migraines, reduce anginal episodes, reduce episodes of anxiety and even treat alcohol withdrawal symptoms (Farooqi and Aboul-Enein, 1995). It is one of the most commonly used classes of these drugs (Aarons et al, 1979) but while propranolol is effective in treating several conditions, toxicity may occur in some cases too and is a result of interaction between the receptor and the drug (Glaubinger and Lefkowitz, 1977). Toxicity can affect cardiac, vascular or bronchial function (Farooqi and Aboul-Enein, 1995).
The beta-adrenergic receptor is a well studied receptor that is phylogenetically conserved (Barak et al, 1994) and is present in low concentrations in plasma membranes (Yarden et al, 1986). It has been demonstrated to be an integral plasma membrane glycoprotein which is hydrophobic (Yarden et al, 1986).
The beta-adrenergic receptor (Refer Fig. 1) is made up of seven transmembrane alpha-helices spanning the plasma membrane. Three of these loops are intracellular while the other three are extracellular. There is an amino terminus and a carboxyl terminus to the receptor of which the carboxyl terminus is on the cytoplasmic side and the amino terminus is inside the cell. This receptor is N-glycosylated near the amino terminus with the amino terminus being blocked in this receptor (Yarden et al, 1986, Green et al,1993). There are many phosphorylation sites on the carboxyl loops (Yarden et al, 1986) which allows for activation.
The chemical name of propranolol is 1-isopropylamino-3-(1-naphthyloxy)-2-propanol (Farooqi and Aboul-Enein, 1995) and it is a beta-adrenergic antagonistic drug (Glaubinger and Lefkowitz, 1977). Different structures have been proposed for this drug (Padke et al, 1981). However, a widely accepted one appears to be one put forward by Phadke et al, 1981 (Refer
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An architect needs to be able to see the forest through the trees, but simultaneously understand how each individual tree serves as an incredibly important part of the forest. Alexander, Lynch, Jacobs and Le Corbusier all take different tacks at understanding the configuration of the city but each has one important component: an incredible focus on the city as existing for the people within it, and the fact that human interactions serve much more to define the structure of a city than any physical layout – so it is an architect’s fundamental job to use the physical layout and structure of a city to shape those interactions however possible.
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