03.02.4.2 Functional

Another type of antagonism is functional antagonism. As always, the endogenous compounds and agonists (Ag) have readily reversible (electrostatic) binding to receptor (Figure 3.25). The functional antagonist binds at site other than the receptor for the endogenous compound to inhibit the response. This site could be the ion channel opened by stimulation of the receptor.

Figure 3.25 Functional antagonism I (Copyright QUT, Sheila Doggrell)

An example of a functional antagonist is verapamil. Verapamil is a Ca²⁺ channel blocker, and as such, a functional antagonist of responses mediated by cardiac b₁-adrenoceptors. Activation of cardiac b₁-adrenoceptors with noradrenaline leads to the opening of calcium channels, and an increase in intracellular calcium increases heart rate. Verapamil reduces noradrenaline-induced increases in heart rate (Figure 3.26). Graphically, with a functional antagonist, there is a non-parallel rightward shift of the concentration-response curves, often with a depression of the maximal response to the agonist.

Figure 3.26 Functional antagonism II (Copyright QUT, Sheila Doggrell)

Verapamil is used clinically to treat an overactive pacemaker.