Agonist intrinsic activity

Expressing the Maximal Response to a Partial Agonist Intrinsic Activity and Efficacy... 

The value for intrinsic activity ranges from 1 for a full agonist to 0 for an antagonist, and the fractional values between these extremes represent partial agonists. Intrinsic activity is a property of both the drug and the tissue in which drug effect is measured. 

Pharmacological efficacy refers to the strength of response induced by occupancy of a receptor by an agonist (intrinsic activity) it is a specialised pharmacological concept. But clinicians are concerned with therapeutic efficacy, as follows. 

High agonist intrinsic activity (lA), resulting from high receptor occupancy leading to maintenance of the pharmacological effect [11]. 

DCI and DCN act as partial agonists (intrinsic activity >0) on some other fi-receptors (e.g. cardiac action, lipid mobilization). 

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. 

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. 

FIGURE 4.19 Correlation of the GTP shift for P-adrenoceptor agonists in turkey erythocytes (ordinates) and intrinsic activity of the agonists in functional studies (abscissae). Data redrawn from [16]. 

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. 

Intercellular adhesion molecule-1, 128 Interfacial inhibition, 159 Intrinsic activity, 44-46 Intrinsic efficacy, 9, 45, 115 Inverse agonism, 49, 108 Inverse agonists... 

Ligands that bind to the receptor, but do not exert a maximal cellular reaction when applied at saturating concentrations are referred to as partial agonists. Their remaining activity is termed intrinsic activity ranging between 0% and 100%. 

An important difference from Ariens s concept of intrinsic activity is that efficacy, unlike intrinsic activity, has no upper limit it is always possible that an agonist with a greater efficacy than any existing compound may be discovered. Also, Stephenson s proposal was not finked to any specific assumption about the relationship between receptor occupancy and the response of the tissue. (Ariens, like A. J. Clark, had initially supposed direct proportionality, an assumption later to be abandoned.) According to Stephenson,... 

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... 

Surratt CK, Johnson PS, Moriwaki A et al. p opiate receptor Charged transmembrane domain amino acids are critical for agonist recognition and intrinsic activity. J Biol Chem 1994 269 20548-20553. 

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