Considerations on pharmacodynamics and pharmacokinetics: Can everything beexplained by the extent of drug binding to its receptor?

It is frequently assumed that pharmacological responses depend solely on th e extent of drug binding to its receptor according to the occupational theo ry. It is therefore presumed that the intensity of the effect is determined by drug concentration at its receptor site, yielding a unique concentratio n-effect relationship. However, when dependence, abstinence, and tolerance phenomena occur, as well as for pharmacological responses in vivo that are modulated by homeostatic mechanisms, the rate of drug input shifts the conc entration-effect relationship. Hence, such responses cannot be explained on the sole basis of the extent of drug binding to its receptor. Information on the cellular and molecular processes involved in the generation of absti nence, dependence, and tolerance will undoubtedly result in the development of pharmacodynamic models allowing a satisfactory explanation of drug effe cts modulated by these phenomena. Notwithstanding, integrative physiology c oncepts are required to develop pharmacokinetic-pharmacodynamic models allo wing the description of drug effects in an intact organism. It is therefore important to emphasize that integrative physiology cannot be neglected in pharmacology teaching and research, but should be considered as an equally valuable tool as molecular biology and other biomedical disciplines for the understanding of pharmacological effects.