General Molecular Concepts of Drug Receptor Action

7 GENERAL MOLECULAR CONCEPTS OF DRUG RECEPTOR ACTION 

The preceding sections have explored classical pharmacological concepts based on the dose-response relationships in tissue or organ preparations. The enormous complexity of living systems and the remoteness of cause from effect (i.e., drug administration from pharmacological action) introduce many complications and artefacts into the study of such relationships. 

This confusion is complicated even further by receptor multiplicity. Consider, for example, the presence of opiate receptors in both the central nervous system and the ileum. Not only do they have different roles as participants in neuromodulation and peristaltic 

Receptor plasticity could be invoked as the underlying common trait of multiple receptors. For example, although the multiple adrenergic isoreceptors are similar, they react to the common neurotransmitter norepinephrine (2.4) in a quantitatively different manner. They also show a drug specificity that varies from organ to organ and differs in various species of animals. In subsequent chapters of this book, receptor multiplicity as the rule rather than the exception will become amply evident. It is to be hoped that, in time, the comparison of isoreceptor molecular structures will provide precise criteria for their differentiation. 

Some members of a receptor population are in the R state, even in the absence of any agonist. Thus, the receptor can be thought of having a tone like a resting muscle. The ratio of states is defined by the equilibrium constants Kp and (for drug D or inhibitor I), and gives true physicochemical meaning to the concept of intrinsic activity. 

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