Surmountable antagonism

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). 

Sole effects on affinity (with no change in receptor function) result in surmountable antagonism. 

The next consideration is to determine whether the antagonism is surmountable or insurmountable (see Figure 10.13). In the case of surmountable antagonism, a Schild analysis is carried out (dose ratios can be used from... 

Used to estimate system independent potency of a partial agonist that produces a submaximal response and surmountable antagonism of agonist response. 

Surmountable antagonism can be quantified by pA2 values. Insurmountable antagonism through IC50 values that in some cases can be corrected for the strength of stimulation in the system. 

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). 

Thus, the two kinetic extremes yield surmountable antagonism(t k2 ) and insurmountable antagonism... 

Sole effects on affinity (with no change in receptor function) result in surmountable antagonism. The dextral displacement reaches a maximal value leading to a curvilinear Schild regression. 

Allosteric Surmountable Antagonism Orthosteric Partial Agonist Inverse Agonist... 

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