Abstract: The operational model of agonism assumes that the maximum effect a particular receptor system can achieve (the Em parameter) is fixed. Em estimates are above but close to the asymptotic maximum effects of endogenous agonists. The concept of Em is contradicted by superagonists and those positive allosteric modulators that significantly increase the maximum effect of endogenous agonists. An extension of the operational model is proposed that assumes that the Em parameter does not necessarily have a single value for a receptor system but has multiple values associated to multiple active receptor conformations. The model provides a mechanistic link between active receptor conformation and agonist efficacy, which can be useful for the analysis of agonist response under different receptor scenarios.

Abstract: Empirical and mechanistic models differ in their approaches to the analysis of pharmacological effect. Whereas the parameters of the former are not physical constants those of the latter embody the nature, often complex, of biology. Empirical models are exclusively used for curve fitting, merely to characterize the shape of the E/[A] curves. Mechanistic models, on the contrary, enable the examination of mechanistic hypotheses by parameter simulation. Regretfully, the many parameters that mechanistic models may include can represent a great difficulty for curve fitting, representing, thus, a challenge for computational method development. In the present study some empirical and mechanistic models are shown and the connections, which may appear in a number of cases between them, are analyzed from the curves they yield. It may be concluded that systematic and careful curve shape analysis can be extremely useful for the understanding of receptor function, ligand classification and drug discovery, thus providing a common language for the communication between pharmacologists and medicinal chemists.

Abstract: Plaque analysis in IVUS planes needs accurate intima and adventitia models. Large variety in adventitia descriptors difficulties its detection and motivates using a classification strategy for selecting points on the structure. Whatever the set of descriptors used, the selection stage suffers from fake responses due to noise and uncompleted true curves. In order to smooth background noise while strengthening responses, we apply a restricted anisotropic filter that homogenizes grey levels along the image significant structures. Candidate points are extracted by means of a simple semi supervised adaptive classification of the filtered image response to edge and calcium detectors. The final model is obtained by interpolating the former line segments with an anisotropic contour closing technique based on functional extension principles.