03.02.4.1 Competitive Reversible

In addition to acting at receptors to mimic the effects of endogenous compounds and initiate cell signaling, drugs can act at receptors as antagonist. Receptor antagonists have affinity, but not efficacy; they have no effect on their own. The most common type of receptor antagonism is competitive reversible. Endogenous compounds and agonists (Ag) have readily reversible (electrostatic) binding to receptor (Figure 3.23).

Figure 3.23 Competitive reversible antagonism I (Copyright QUT, Sheila Doggrell)

Competitive reversible antagonists have readily reversible binding to same site on receptor as the agonist. Increasing the concentration of the antagonist, decreases the concentration of the agonist bound to the receptor, and the resulting effect. Importantly, the effects of a competitive reversible antagonist can be overcome by increasing the concentration of the agonist, and this is useful in poisoning.

Atenolol is an example of a competitive reversible antagonist. Atenolol is a competitive reversible antagonist at b₁-adrenoceptors, which means it has no effect alone (Figure 3.24). However, atenolol decreases the amount of noradrenaline (NA) bound to receptors, and this decreases the effect of noradrenaline. On the heart, noradrenaline increases heart rate and force, and for any concentration of noradrenaline, atenolol will decrease the ability of noradrenaline to increase heart rate and force (Figure 3.24).

Figure 3.24 Competitive reversible antagonism II (Copyright QUT, Sheila Doggrell)

The graph shows that the higher the concentration of atenolol, the greater the inhibition of the response to noradrenaline. Atenolol causes a parallel rightward shift of the noradrenaline concentration response, but if you add enough noradrenaline, a maximum response is obtained. Atenolol is used clinically as an anti-hypertensive drug.