Allosteric modulator

A chemical that increases or decreases the strength of the signal a receptor sends into the cell.

A chemical that increases or decreases the strength of the signal a receptor sends into the cell. Allosteric modulators affect constitutive activity and agonists, but their effect will not necessarily be the same for all agonists of a receptor.

Summary from Wikipedia:

In biochemistry and pharmacology, an allosteric modulator (allo- from the Greek meaning "other") is a substance which indirectly influences (modulates) the effects of a primary ligand that directly activates or deactivates the function of a target protein. Targets may be metabotropic, ionotropic and nuclear receptors, enzymes and transporters. Allosteric modulators bind to a site distinct from that of the orthosteric binding site. They stabilize a conformation of the protein structure that affects either the binding or the efficacy of the primary ligand. Pure modulators have no direct effect on the function of the protein target. The modulatory properties are interdependent with the ternary complex consisting of the target protein, the primary ligand and the modulator.

Positive allosteric modulators (PAMs), also known as allosteric enhancers or potentiators, induce an amplification of the effect of receptor's response to the primary ligand without directly activating the receptor. Most benzodiazepines act as PAMs at the GABAA receptor.

Negative allosteric modulators (NAMs) act at an allosteric site to reduce the responsiveness of the receptor to the endogenous ligand. Ro15-4513 is a NAM at the α1β2γ2 GABAA receptor.

Silent allosteric modulators (SAMs), also called neutral or null modulators, occupy the allosteric binding site and behave functionally neutral. Flumazenil can be regarded as such an example.

The modulatory activity can be first-order, second-order, or both. Second-order modulators alter the modulatory activity of first-order modulators, whereas first-order modulators do not alter the activity of other allosteric modulators. (−)‐Epigallocatechin‐3‐gallate is one such example of a second-order modulator at GABAA receptors.

Read more