Antagonism competitive, dose-response

FIGURE 6.1 Effects of antagonists on agonist dose-response curves, (a) Surmountable antagonism with no diminution of maxima and no limiting antagonism (competitive antagonists). 

There are patterns of dose-response curves that preclude Schild analysis. The model of simple competitive antagonism predicts parallel shifts of agonist dose-response curves with no diminution of maxima. If this is not observed it could be because the antagonism is not of the competitive type or some other factor is obscuring the competitive nature of the antagonism. The shapes of dose-response curves can prevent measurement of response-independent... 

The squared deviations between the calculated and actual responses are shown in Table 12.6c (see column labeled SSq). The AIC values are calculated according to Equation 11.30. The values are shown in Table 12.6c. It can be seen that the fit to the curves with a mean Emax and slope gives a lower AIC value. Therefore, this model is statistically preferable. It is also the most unambiguous model for simple competitive antagonism since it fulfills the criteria of parallel dextral displacement of dose-response curves with no diminution of maxima. The calculated curves are shown in Figure 12.7b. 

Schild analysis, this powerful method of quantifying the potency of a competitive antagonist was developed by Heinz Schild (Br. J. Pharmacol. 14,48-58, 1959 see Chapter 6.3). It is based on the principle that the antagonist-induced dextral displacement of a dose-response curve is due to its potency (K% value) and its concentration in the receptor compartment. Because the antagonism can be observed and the concentration of antagonist is known, the KB can be calculated. 

Surmountable antagonism, an antagonist-induced shift to the right of an agonist dose-response curve with no diminution of the maximal response to the agonist (observed with simple competitive antagonists and some types of allosteric modulators). 

Fig. 1.5.2 Log dose response curve showing competitive antagonism.

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