AN ELECTROPHYSIOLOGICAL APPROACH TO DRUG-RECEPTOR MECHANISMS

1. 1. Analysis of current knowledge of the pharmacology of excitable tissues makes possible the characterization of drug-receptor interactions. The most discriminating tool for such characterization measurement of conductance change in a single cell as a function of the concentration of the drug. Other measurements, including voltage change and equilibrium potential measurements, can be shown to be less useful. 2. 2. The limiting slope of the log-log plot of conductance against concentration as concentration is lowered equals the smallest number of molecules that must interact with a receptor unit to produce any conductance change. Expressions relating conductance and concentration can then be generated and experimentally checked and an affinity constant thereby derived. 3. 3. The concept of efficacy is related to the mean conductance change produced by activation of one receptor. The use of the relative unt conductance as a measure of efficacy is shown to be valid in situations where other likely measures are useless. 4. 4. Finally, it is shown that two or more molecules of drug are required to activate one receptor in a number of excitable tissues. 5. 5. Methods for quantitative characterization of the drug receptor interaction are indicated. © 1969.