Full agonist definition

The pA2 calculation is derived by equating the response produced by the full agonist in the absence of the inverse agonist (Equation 6.64 with [B] = 0) to the response in the presence of a concentration of the inverse agonist that produces a dose ratio of 2 (by definition the pA2). For calculation of KB from 10-pAT... 

FIGURE 10.7 Figure illustrating the comparison of concentration-response curves to two full agonists. Equations describe response in terms of the operational model (variable slope version equation see Section 10.6.1). Schematic indicates the interacting species in this case, two full agonists A1 and A2 activating a common receptor R to produce response. Boxes show the relevant measurements (EPMRs) and definitions of the parameters of the model used in the equation. 

Intrinsic activity Intrinsic activity is the maximal stimulatory response induced by a compound in relation to that of a criven reference compound. This term has evolved with common use. It was introduced by Ariens as a proportionality factor between tissue response and receptor occupancy. The numerical value of intrinsic activity (alpha) could ran from unity (for full agonists, i.e., agonist inducing the tissue maximal response) to zero (for antacyonists). The fractional values within this ran denoting partial agonists. Arien-8 original definition equates the molecular nature of alpha to maximal response only when response is a linear function of receptor occupancy. This function has... 

BZD agonists and inverse agonists can be further sub-divided based on their intrinsic activity i.e. whether they have full or partial modulatory capacity. Because BZD compounds exert only modulatory effects, there may be no absolute definition of a full agonist or inverse agonist. However, the maximum modulatory effect can differ widely for example, the maximum ability of diazepam (2), lorazepam (3), and alprazolam (6) to potentiate the activity of GABA is much greater than that of bretazenil (16) or abecarnil... 

Hoyer, D. and Boddeke, H.W.G.M. (1993) Partial agonists, full agonists, antagonists dilemmas of definition. Trends Pharmacol. Sci. 14 270-273. 

F. Efficacy Efficacy, often called maximal efficacy, is the maximal effect (E,.,.,) an agonist can produce if the dose is taken to very high levels. Efficacy is determined mainly by the nature of the receptor and its associated effector system. It can be measured with a graded dose-respon.se curve (Figure 2-1) but not with a quantal dose-response curve. By definition, partial agonists have lower maximal efficacy than full agonists (see below). 

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