Antagonist noncompetitive

This is formally identical to the equation derived by Gaddum and colleagues [3] (see Section 6.8.2) for noncompetitive antagonism. In this case, it is assumed that the only available receptor population in the presence of a fractional receptor occupancy pB by a noncompetitive antagonist is the fraction l-pB. Thus, agonist receptor occupancy is given by... 

Historically, Gaddum and colleagues [3] devised a method to measure the affinity of insurmountable antagonists based on a double reciprocal linear transformation. With this method, equiactive concentrations of agonist in the absence ([A]) and presence ([A ]) of a noncompetitive antagonist ([B]) are compared in a double reciprocal plot... 

In cases where there is a substantial receptor reserve such that there is a measurable dextral displacement of the concentration response curves, then another reliable method for determining the affinity of the noncompetitive antagonist is to measure the pA2 (—log of the molar concentration that produces a twofold shift to the right of the agonist concentration-response curve). It can be shown that for purely noncompetitive antagonists the pA2 is related to the pKB with the relation (see Section 6.8.10)... 

In this model, it is assumed that the noncompetitive antagonist reduces the fraction of available receptor population. Therefore, equating stimuli in the absence and presence of noncompetitive antagonist ... 

An analogous procedure can equate the empirical pA2 to pKB for noncompetitive antagonists. Utilizing the equation for agonist response in the presence of a noncompetitive antagonist (Equation 6.10), equiactive concentrations with a dose ratio of 2 in the presence and absence of antagonist is given by ... 

Erroneous Application of Correction Factors to Noncompetitive Antagonists... 

Method of Goddam for Measurement of Noncompetitive Antagonist Affinity... 

Aim This method is designed to measure the affinity of a noncompetitive antagonist. 

General Procedure Dose-response curves to a full agonist are obtained in the absence and presence of the noncompetitive antagonist. From these curves, equiactive concentrations of full agonist are compared in a linear regression (see Section 12.2.1). The slope of this regression is used to estimate the KB for the noncompetitive antagonist. 

Aim This method is designed to measure the affinity of a noncompetitive antagonist, which produces depression of the maximal response of the agonist concentration-response curve with no dextral displacement. 

Gadduin analysis, Gadduin (method of), this method (Q. J. Exp. Physiol. 40, 49-74, 1955) compares equiactive concentrations of an agonist in the absence and presence of a concentration of noncompetitive antagonist that depresses the maximal agonist response. These are compared in a double reciprocal plot (or variant thereof) to yield the equilibrium dissociation constant of the noncompetitive antagonist-receptor complex (see Chapters 6.4 and 12.2.8). 

Gadduin equation (noncompetitive antagonism), this technique measures the affinity of a noncompetitive antagonist based on a double reciprocal plot of equiactive agonist concentrations in the absence and presence of the noncompetitive antagonist. The antagonist must depress the maximal response to the agonist for the method to be effective see Chapter 6.4. 

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