Allosteric Modulator
A substance that binds to a receptor at a site other than the primary (orthosteric) binding site and modifies the receptor's response to its natural ligand. Positive allosteric modulators enhance the ligand's effect while negative allosteric modulators reduce it. This approach allows fine-tuning of receptor activity.
Technical Context
Allosteric modulators bind to sites distinct from the orthosteric (primary ligand) binding site. Positive allosteric modulators (PAMs) enhance the affinity or efficacy of the natural ligand without activating the receptor independently. Negative allosteric modulators (NAMs) reduce the natural ligand's effect. This approach offers advantages over direct agonism or antagonism: it preserves the temporal pattern of endogenous signalling (enhancing or dampening rather than replacing), may offer greater receptor subtype selectivity (allosteric sites are less conserved than orthosteric sites), and avoids complete receptor blockade. Allosteric modulation is an emerging strategy in peptide receptor pharmacology.