03.02.2.3 Potency and Selectivity of Agonist

Potency and selectivity are two other properties of agonists that are important in determining whether they will useful clinically. Potency is measured as the half-maximal response to the drug being tested. The parameter is known as the EC₅₀, the concentration of agonist that causes have maximal response. From the graph, the maximal response is determined, and for 50% of that, the EC₅₀ value is read off (Figure 3.19).

Figure 3.19 Measuring agonist potency (Copyright QUT, Sheila Doggrell)

Regardless of whether the agonist is a full agonist or a partial agonist, EC₅₀ values are measured at half the maximal response to the agonist. The lower the EC₅₀ value, the more potent the agonist is. In the Figure 3.14, the full agonist is more potent than the partial agonist, but it is possible to have partial agonists that are more potent than full agonists. Clinically, potent agonists are usually preferable, especially if they are also selective.

A drug that has a greater potency at receptor A than receptor B, is selective for receptor A, but is still capable of having effect at receptor B. A drug that is potent at receptor A and has no effect at other receptors would be specific for receptor A, and would not be capable of having effects at other receptors. Drugs are usually selective not specific.

Potency and selectivity go hand in hand, and can be illustrated by comparing noradrenaline and isoprenaline. Noradrenaline, the neurotransmitter released from the sympathetic nervous system, acts on cardiac b₁-adrenoceptors to increase heart rate. Isoprenaline is a synthetic drug that has a similar structure to noradrenaline. On the cardiac b₁-adrenoceptors, isoprenaline is more potent (has a lower EC₅₀) value than noradrenaline (Figure 3.20).

Figure 3.20 Potency and selectivity at β₁-adrenoceptors (Copyright QUT, Sheila Doggrell)

Noradrenaline released from the sympathetic nervous system, also acts on vascular a₁-adrenoceptors to cause vasoconstriction. At the vascular a₁-adrenoceptors, isoprenaline is much less potent (has a higher EC₅₀) value than noradrenaline (Figure 3.21).

Figure 3.21 Potency and selectivity at α₁-adrenoceptors (Copyright QUT, Sheila Doggrell)

Taken together, these graphs show that noradrenaline does not select, but isoprenaline is selective for b₁- over a₁-adrenoceptors. Thus, if we want to selectively mimic the effects of noradrenaline at b₁-adrenoceptors, it is better to use isoprenaline than noradrenaline, as noradrenaline will have effects elsewhere, which could be detrimental effects.