Dose-response curve, essential

General Procedure Full dose-response curves to a full and partial agonist are obtained in the same receptor preparation. It is essential that the same preparation be used as there can be no differences in the receptor density and/or stimulus-response coupling behavior for the receptors for all agonist curves. From these dose-response curves, concentrations are calculated that produce the same response (equiactive concentrations). These are used in linear transformations to yield estimates of the affinity of the partial agonist. 

Fig. 11.2 A hypothetical dose - response curve for an essential nutrient.

Every essential element follows a dose-response curve, shown in Figure 1.1, as adapted from reference 2. At lowest dosages the organism does not survive, whereas in deficiency regions the organism exists with less than optimal function. 

Figure 1.1 Dose-response curve for an essential element. (Adapted with permission from Figure 3 of Frieden, E. J. Chem. Ed., 1985, 62(11), 917-923. Copyright 1985, Division of Chemical Education, Inc.)...

Other dose-response relationships may also be seen for certain compounds such as, e.g., essential metals, where symptoms of dehciency may occur if the intake is too low, whereas toxic symptoms may occur if the intake is too high. For such compounds, the dose-response curve is generally U-shaped as illustrated in Figure 4.2. It should be noted that the right part of the U-shaped curve representing the toxic effects in reality is the typical S-shape observed for toxic effects in general. 

As mentioned in Section 4.2.3, a single smdy may reveal different types of effects and in principle, a dose-response curve can be recorded for each type of effect observed in the smdy as illustrated in Figure 4.5. If a single smdy reveals different types of effects, it is essential to evaluate all these effects in terms of their NOAELs and LOAELs. The overall NOAEL for a particular smdy is often, but not necessarily, the lowest NOAEL derived for the various effects. 

In particular, we would emphasize the need to obtain full dose-response curves and a careful assessment of potency differences and efficacy differences based on these full dose-response relationships. This is critical If one Is to develop Insight Into those features of structure and conformation which are critical to receptor recognition and those which are critical to transduction (, ). Such Insight Is essential In the development of antagonists, superagonists, etc. 

The benchmark dose method and MOE analyses are essentially the same for substances that cause stochastic or deterministic effects. For both types of substances, the point of departure in the dose-response curves for purposes of protecting human health is a dose at which some response is expected, either LED10 or some other human equivalent dose or concentration as the data support. For stochastic responses (e.g., cancers), the point of departure when animal data are used is a human equivalent dose or concentration... 

In all cases information on the dose-response of effects is essential to identify the slope of the dose response curves, possible thresholds, the NOEL, LOEL or the maximal tolerated dose (MTD). For most of the tests guidelines are available (see OECD or European Communities). 

Graphical interpolation essentially is the plotting of the dose-response curve and reading the concentration that corresponds to the LC50 or the LC10. 

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