Receptors drug-target residence time

The idea of drug-target residence time places less emphasis on the strength of receptor-ligand interaction and more emphasis on the duration of receptor-ligand interaction. The duration of interaction is defined as the residence time (t) of the ligand, which is equal to the inverse of koff (Equation 5.23). A closely related variable is dissociative half-life (/, 2), also defined by koll (Equation 5.24).31... 

Long-acting P-2-adrenergic drugs show a prolonged pulmonary residence time because of a specific interaction of these drug molecules with their cellular targets. It has been shown that salmeterol binds reversibly to an active site on the P2-receptor and irreversibly to an exosite, which may be a domain adjacent to the active site within the P2 -receptor in the lipid bilayer of the cell membrane... 

Generally, a targeted strategy to determine the relationship between structure and poteney of inhibitors using an isolated receptor enzyme cannot take into account the many pitfalls and complexities of the in vivo system arising at different points for example, the tissue level and the half-time of the inhibitor, the concentration and reserve capacity of the enzyme [34,74], and the residence time of the inhibitor at its binding site. This is stated here only to indicate that the inhibitors characterized in the Na /K -ATPase test (Tables 4.1-4.5) are not necessarily meant to serve as potential drugs. 

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