Agonism and antagonism

A drug which binds to a specific receptor (affinity) and, once bound, is able to produce a response (intrinsic activity). 

A drug that has significant affinity but no intrinsic activity. 

A drug that produces a maximal response once bound to the receptor. 

A drug with significant affinity but submaximal intrinsic activity. 

Line A This line shows the opposite effect where there is no initial full agonist present and hence no initial response. As more partial agonist is added, the response rises to the maximum possible (50%) and so in this instance the partial agonist has behaved as an agonist by increasing the response seen. 

---

FIGURE 9.17 Venn diagram consisting of the various possible activities (agonism and antagonism) on two receptor subtypes (a- and P-adrenoceptors). Letters label the areas of intersection denoting joint activity. The table shows possible therapeutic application of such joint activity. 

Brzozowski AM, Pike AC, Dauter Z (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389 753... 

A potential limitation of this approach is that the conformational information that would enable decisions to be taken about agonism and antagonism, etc. has been lost. It is, however, possible to establish rules which go a long way to overcome this limitation. For example, interaction with Themes in the bottom left quadrant is likely to produce antagonists, whereas interaction with the Themes in the top left quadrant of the logical map to produce agonists is preferred. 

Recall that there are many possibilities for drug action in the nervous system besides agonism and antagonism. We will now consider species which can enhance or deplete the concentration of a neurotransmitter in the synaptic cleft. 

The structural manipulation at different positions of adenosine provided a wide number of ligands at the A3 AR exerting different levels of potency, selectivity, and intrinsic efficacy. The exact combination of modifications showed to affect the balance between full agonism, partial agonism and antagonism (Joshi and Jacobson 2005). 

Structural Basis for Agonism and Antagonism and Partial Agonism The Role of the Ligand... 

Brzozowski, A. M. et al. Molecular Basis of Agonism and Antagonism in the Estrogen Receptor, Nature 1997, 389, 753-758. 

Explicit studies of opiate-receptors interactions should be very useful in continuing to explore the factors that modulate the extent of agonism and antagonism in a given opiate and the variation in this ratio among closely related analogues. Such studies are severely hampered on the experimental side by the lack of a detailed description of the opiate binding site. 

Agonism and antagonism of the compounds for muscarinic receptors have been measured in functional and binding experiments usmg the preparations listed below ... 

---