Competitive antagonism studies

Among the numerous variations made around the a-methyl-DOPA molecule, acylation with a glycyl-glycyl residue was claimed to improve oral bioavailability. For a series of anticandidal di- and tripeptides containing m-fluorophenylalanine (m-FPhe), competitive antagonism studies supported peptide transport-mediated entry of the warhead m-FPhe inside the cell. Dipeptides derived from a-methyldopa (Fig. 33.9) show a 10 to 20-fold better penetration of the intestinal wall than a-methyldopa itself. 

This is the Schild equation, which was first stated and applied to the study of competitive antagonism by H. O. Schild in 1949. It is probably the most important single quantitative relationship in... 

Practical Applications of the Study of Reversible Competitive Antagonism... 

The quantitative study of competitive antagonism by the methods just described has important uses ... 

When studying competitive antagonism, it is sometimes necessary to include an uptake inhibitor or a ganglion blocker in all the bathing solutions used. If this compound has in addition some competitive blocking action at the receptor being studied, what effect will this have on estimation of the dissociation equilibrium constant for a competitive antagonist ... 

More recently the drug has been re-examined to elucidate its properties more thoroughly [230-1]. The first of these studies [230] demonstrated that thymoxamine satisfied the usual criteria [232-7] for competitive antagonism at a-receptor sites (against noradrenaline) but showed no (3-receptor blocking... 

Sigmoid Emax Model Jonkers and colleagues [80] studied the pharmacodynamics of racemic metoprolol, a cardioselective beta-blocker, and the active S-isomer in extensive metabolizers (EMs) and poor metabolizers (PMs). The drug effect studied was the antagonism by metoprolol of terbutaline-induced hypokalemia (abnormally low potassium concentration in the blood). The pharmacodynamic interaction was described by a sigmoidal function for competitive antagonism based on the earlier work of Holford and Sheiner [81] ... 

Recently Wohl (30) reported on extensive studies on the competitive antagonism of Ca2+-induced rat aortic vasoconstriction in vitro by a series of 36 benzothiadiazines. The Extended Huckel Theory (EHT) was used to calculate the preferred tautomer in solution, and charges, etc., on all atoms. The final equation was fairly successful in predicting the activity of several moderately potent compounds not included in the original regression. 

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