Question

why partial agonist is unable to reach the maximal response?

Answer 1

A partial agonist does not reach the maximal response proficiency of the system even at full receptor occupancy.

The effect of a drug is proportional to the number of receptors occupied by the drug and that maximal effect results when all receptors are found occupied. But this assumption may only be true for a limited number of cases. The relationship between the effect caused by a drug and the concentration of drug-receptor complexes.

E = α[DR]

where E is the effect

α is the proportionality constant of the drug

[DR] is the concentration of the drug - receptor complex

This relationship showed that some drugs do not show a maximal response even at ostensibly maximal receptor occupancies. These drugs are called partial agonists.

Why - The differences in the effects of a drug in different tissues are a reflection of the impact of properties of the drug, properties of the receptor, and properties of a tissue in terms of receptor density, and the coupling of receptor occupancy to the ultimate response. Partial agonists by quality of the work of a large number of receptors without impacting a response, competitively block the effects of agonists of higher intrinsic efficacies or full agonists. Both effects of the partial agonist are the result of the interaction with the same site, antagonism from partial agonists should be observed at the same concentrations that produce the agonist effect.