Types Of Allosteric Modulators And Their Properties

Allosteric modulators have a vast array of potential effects. For instance, they can enhance orthosteric ligand affinity and/or efficacy, inhibit orthosteric ligand affinity and/or efficacy, or even act as allosteric agonists/inverse agonists in their own right (Fig. 3.2a). Moreover, some of these properties can change dramatically, depending on the nature of the orthosteric ligand with which the modulator is interacting. Thus, it is not surprising that there have been a number of phenomenological descriptors, some more confusing and/or cryptic than others, applied to allosteric modulators. It should also be noted that there is no reason why a modulator could not express more than one of these properties concomitantly, for example, agonism (positive or inverse) together with enhancement or inhibition of orthosteric ligand binding/function [19, 22]. For example, alcuronium, an allosteric modulator of muscarinic acetylcholine receptors (mAChRs), is an inverse (allosteric) agonist, an allosteric enhancer of the affinity of the orthosteric antagonist, [3H]N- methylscopolamine, an allosteric inhibitor of the affinity of the orthosteric antagonist, [3H]quinuclidi-nyl benzilate, and an allosteric inhibitor of the efficacy of the orthosteric

Affinity

(a) Modulation

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