Intrinsic activity, defined

The term intrinsic activity (ia) was defined as a measure of the abiUty of the dmg—receptor complex to generate response. When ia = 1, a full agonist is defined when ia = 0, an antagonist is defined. Thus, values 0 < ia < 1 define partial agonists as follows, where R is the response to dmg and R is the maximum response achieved. 

Let us define the activation energy for a (possible hypothetical) thermoneutral reaction as the intrinsic activation energy, AEq. As seen from eq. (15.10), a = 4A q. The TS position and activation energy now become... 

FIGURE 3.7 Principal components of the operational model. The 3D array defines processes of receptor occupation (plane 1), the transduction of the agonist occupancy into response (plane 2) in defining the relationship between agonist concentration, and tissue response (plane 3). The term a refers to the intrinsic activity of the agonist. 

Relative intrinsic activity, this actually is redundant, as intrinsic activity itself is defined only in relative terms, i.e., the maximal response of an agonist as a fraction of the maximal response to another agonist. 

Before deriving the rate equations, we first need to think about the dimensions of the rates. As heterogeneous catalysis involves reactants and products in the three-dimensional space of gases or liquids, but with intermediates on a two-dimensional surface we cannot simply use concentrations as in the case of uncatalyzed reactions. Our choice throughout this book will be to express the macroscopic rate of a catalytic reaction in moles per unit of time. In addition, we will use the microscopic concept of turnover frequency, defined as the number of molecules converted per active site and per unit of time. The macroscopic rate can be seen as a characteristic activity per weight or per volume unit of catalyst in all its complexity with regard to shape, composition, etc., whereas the turnover frequency is a measure of the intrinsic activity of a catalytic site. 

In 1954 the Dutch pharmacologist E. J. Aliens introduced the term intrinsic activity, which is now usually defined as ... 

The efficacy of a particular agonist, as defined by Stephenson, can vary between different tissues in the same way as can the intrinsic activity, and for the same reasons. Moreover, the value of both the intrinsic activity and the efficacy of an agonist in a given tissue will depend on the experimental... 

The activity, which may be defined as the net rate of S02 oxidation in moles/s/m3 catalyst according to reaction (1), depends on the intrinsic activity of the catalyst material, the diffusion properties of the catalyst material, the size of the catalyst pellets, and the shape of the pellets. 

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. 

Because of their variable thermodynamic state and concentration each reactant or product is characterized at any instant by an intrinsic activity, a, and the interplay between these activities defines the chemical action A, at that instant. The action changes at a rate proportional to A and to the change in affinity, as summarized by the linear homogeneous equation ... 

Receptors can be most reliably subclassified and defined on the basis of antagonist affinities, whereas data obtained with agonists are considered much less useful since intrinsic activity and potency have been found to be cell and tissue dependent. Information on receptor-effector mechanisms that reflect the molecular signaling properties of the receptor provides another tier for receptor classification, although transduction mechanisms for novel receptors may be unclear and subject to controversy. Furthermore, the use of heterologous cellular expression systems for the study of recombinant receptors has revealed... 

The performance of a catalyst is determined by its intrinsic activity and dispersion. This latter is defined as the ratio between the number of surface and bulk atoms. Metal nanoparticles supported on a high-surface-area carbon are thermodynamically unstable and give rise to sintering phenomena upon thermal treatment. In this regard, the influence of the nature of the support on the properties of dispersed catalysts has been continuously investigated [2]. For fuel cell catalysts, carbon support provides a framework that allows electron conduction and enhances the dispersion of the active phase. 

Various catalysts are used in different commodity epoxidation processes at diverse conditions. Important characteristics are the space time yield based on the weight of epoxide formed per kilogram of catalyst, and the TOF as a measure of the intrinsic activity per active surface metal atom (Table 1.4). In Table 1.4 and other tables in this chapter, conversion is always based on the reactant olefin and not on the oxidant, unless specified. Selectivity refers to the epoxide product, and yield to the product of conversion and selectivity, unless defined otherwise. 

As applied to proton transfers, the theory takes the form of equations 1.7 and 1.8, where kdiff is the diffusion-controlled encounter rate. AG is the free energy of activation defined by equation 1.8, AG° being the standard equilibrium free energy change and AG the intrinsic barrier , the free energy of activation when AG° = 0, a constant of the particular type of reaction. 

The partial agonist concept was additionally refined by Stephenson (33), who introduced the concept of efficacy, e, which differed from intrinsic activity in that the latter was defined as a proportion of the maximal response [effect = a (RL)]. This concept was extended to situations where a maximal response to an agonist could occur when only a small proportion of the total number of receptors on a tissue were occupied, as in the situa-... 

The Br0nsted equation, which is empirical, can be viewed as being a special case of the Marcus equation, which was derived from first principles. The latter theory has the important added feature of defining intrinsic activation barriers. 

The strength of the reversible interaction between a drug and its receptor, as measured by their dissociation constant, is defined as the affinity of one for the other. Both the affinity of a drug for its receptor and its intrinsic activity are determined by its chemical structure. 

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