A practical approach to estimate the potency of an antagonist in a functional experiment with isolated preparations...

The potency of an antagonist is a key concept in pharmacology, with multiple implications that range from the basic science to the clinical scenario, e.g., from receptor characterization to the dosage schedule of a patient. However, teaching the concept of antagonist potency may be a challenge because, unlike agonists, antagonists lack intrinsic efficacy, meaning they do not activate the receptor they bind to produce a biological response. In experiments in isolated tissues without spontaneous tonus, such as the rat aorta, students might observe that prazosin (an antagonist of α₁-adrenergic receptors) does not induce observable effects alone, although it is able to relax a contraction elicited by phenylephrine (α₁-adrenergic agonist) because prazosin competitively antagonizes phenylephrine at α₁-adrenoceptors. Experimental approaches to analyzing antagonist potency have been proposed, with the Schild method being the most widely accepted. However, such an analysis can be time-consuming if adopted in a practical class because it necessitates the generation of complete concentration-response curves for an agonist under control conditions and in the presence of a series of increasing concentrations of an antagonist. Alternative methods, such as the Cheng-Prusoff approach, have been proposed to estimate the value of the equilibrium dissociation constant (K_b) in functional studies, a parameter that represents the affinity of the antagonist for one receptor. Based on these approaches, the present study proposes an experimental protocol designed to help students understand the concept of antagonist potency using phenylephrine and prazosin in isolated rat aorta preparations.NEW & NOTEWORTHY By utilizing phenylephrine and prazosin in isolated rat aortas, students can better understand the concept of antagonist potency. This activity provides a practical opportunity to discuss key aspects of cell-drug interactions, including efficacy and intrinsic activity, via parameters such as EC₅₀, IC₅₀, equilibrium dissociation constant (K_b), and antagonist potency (pA₂).