Receptor Affinity

The fraction of all receptors that bind drug molecules is determined by the concentration of the drug in the vicinity of the receptor and by the dissociation constant of the drug-receptor complex. (The dissociation constant expresses the relationship between the rates of dissociation from and binding to the receptors, being essentially the ratio of the off-and-on rates of drug receptor complex formation. It depends, most importantly, upon the chemical nature of the molecules involved in the interaction.) When we compare the dose-response curves of two drugs, apomorphine and quinpirole, on Fig. A.3, it is obvious that these drugs produce the same maximal effect. Nevertheless, for any given degree of response, a higher concentration of quinpirole is required if compared to apomorphine. If we assume that the size of the effect of a drug depends upon the proportion of receptors it occupies, we must conclude that quinpirole occupies fewer receptors at any given concentration. The measure that characterizes the ability of a drug in a given concentration to occupy respective receptors is affinity. Affinity can also be said to express the probability with which drug molecules (at a certain concentration) interact with receptors to form the drug-receptor complexes. A drug with a higher affinity is more capable of occupying receptors than one with a lower affinity, and in case their concentrations are equal the one with higher affinity outcompetes the other at the receptors. In our example, apomorphine has a higher affinity than quinpirole for their target (D2 dopamine receptor), and hence lower doses of apomorphine are likely to elicit maximal (or, e.g., half-maximal) effect mediated via these receptors.

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