Appendix 1.4C Analysis of Methods 1 and 2 in Section

Analysis of Method 1 (Section 1.4.8) proposed for the determination of the efficacy of a partial agonist acting on an intact tissue  

Analysis following Stephenson s formulation of efficacy, and using his assumptions and terms. 

For a half-maximal response, 5=1 (by Stephenson s convention) and pAR = [A],. ATa. This approximation holds because if A occupies few receptors (i.e., [A] KA), then 

When the partial agonist P occupies all the binding sites in order to produce its maximal response, pPR = 1. Hence, the stimulus (5P) attributable to P is simply eP Assuming that the same tissue response, whether elicited by A or by P, corresponds to the same value of 5, we can write  

Analysis based on redefining the stimulus as the product of efficacy (e ) and the total receptor occupancy by the agonist (i.e., PiKi)  

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