An alternative method to evaluate the nature of an antagonist and its potency: a theoretical approach.
The Schild analysis is certainly the most reliable method for antagonism studies. The Schild regression allows one to determine the parameter of the Schild-slope, which represents a powerful diagnostic tool when investigating the nature of an antagonist and, consequently, to evaluate its potency. Nevertheless, in functional pharmacology, often practical reasons lead the experimenter to obtain an inhibition curve for the antagonist and calculate its potency by means of equations, which can be considered as a derivation of the Cheng-Prusoff analysis. This approach is considered theoretically invalid, because it does not allow to know the exact nature of the antagonism, and thus the evaluation of the antagonist dissociation constant can be meaningless. In this paper, a new method is proposed, which, by means of an equation closely similar to the Schild one, permits one to obtain a linear regression analysis, giving a slope value absolutely equivalent to the Schild-slope. This method allows us to determine both the nature and the potency of an antagonist, and requires an experimental procedure substantially analogous to the one performed to obtain an inhibition curve.
Calderone
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Istituto Policattedra di Discipline Biologiche, Facoltà di Farmacia, Università degli Studi di Pisa, Italy.
D001667:Binding, Competitive; D007700:Kinetics; D016014:Linear Models; D008432:Mathematical Computing; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*
D011956:Receptors, Cell Surface