Drug—receptor interactions

T. Kenakin, Pharmacological Analysis of Drug Receptor Interaction, 2nd ed.. Raven, New York, 1993 D. Oksenberg and co-workers. Nature, 360, 161 (1992). 

II. RELATIONSHIPS BETWEEN EXPERIMENTAL AND THEORETICAL APPROACHES TO STUDYING DRUG-RECEPTOR INTERACTIONS... 

Figure 1 A flow chart of experimental information about drug-receptor interaction. The objects of experimental and theoretical investigation are boxed, and the experimental information is circled.

Figure 2 A flow chart of theoretical modeling drug-receptor interaction and relation to experiment. The objects of theoretical investigation are m rectangles, and the experimental information IS m the ovals.

A classic example of where definitive experimental data necessitated refinement and extension of a model of drug-receptor interaction involved the discovery of constitutive receptor activity in GPCR systems. The state of the art model before this finding was the ternary complex model for GPCRs, a model that cannot accommodate ligand-independent (constitutive) receptor activity. 

Mathematical models are the link between what is observed experimentally and what is thought to occur at the molecular level. In physical sciences, such as chemistry, there is a direct correspondence between the experimental observation and the molecular world (i.e., a nuclear magnetic resonance spectrum directly reflects the interaction of hydrogen atoms on a molecule). In pharmacology the observations are much more indirect, leaving a much wider gap between the physical chemistry involved in drug-receptor interaction and what the cell does in response to those interactions (through the cellular veil ). Hence, models become uniquely important. 

Kenakin, T. P. (1997). The pharmacologic analysis of drug receptor interaction, Third edition. Lippincott-Raven, New York. 

As noted in Chapter 1, the most simple and theoretically sound model for drug-receptor interaction is the Langmuir adsorption isotherm. Other models, based on receptor behavior (see Chapter 3), are available. One feature of all of these models (with the exception of some instances of the... 

Drug-Receptor Interaction. Figure 2 Relationships between affinity and efficacy with different agonist response patterns, (a) For partial agonists, differences in maximal responses between agonists relate to differences in efficacy. Differences in the location parameter of the concentration-response curve (potency) indicate differences in affinity, (b) For full agonists, differences in potency indicate differences in either affinity, efficacy or both. 

EEG is the abbreviation for Electroencephalogram. Potency Drug-Receptor Interaction... 

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