In biochemistry and pharmacology, an
allosteric modulator (
allo- from the Greek meaning "other") is a
substance which indirectly influences (modulates) the effects of an
agonist or
inverse agonist at a
target protein, for example a
receptor. Allosteric modulators bind to a site distinct from that of the orthosteric agonist
binding site. Usually they induce a
conformational change within the
protein structure. A positive allosteric modulator (PAM) or allosteric enhancer induces an amplification of the orthosteric agonist's effect, either by enhancing the
binding affinity or the
functional efficacy of the orthosteric agonist for the target protein. A negative modulator (NAM) reduces the effects of the orthosteric
ligand, but is inactive in the absence of the orthosteric ligand. Substances that occupy the allosteric binding site and are functionally neutral are called silent allosteric modulators (SAMs). Classic
benzodiazepines are well-known PAMs.