Table 1 Terms and definitions for allosteric synagics (see Figure 1)

orthoster

primary ligand, binds at orthosteric (primary) receptor binding site and covers ligands as agonists, inverse agonists and (neutral) antagonists

alloster or allosteric modulator

secondary ligand, binds to a non-overlapping (secondary or allosteric) binding site distinct from an orthosteric binding site

ago-alloster

an alloster which can activate the receptor even in the absence of an orthoster, but with ceiling for the increased activity

allo-agonism

the effect of an ago-alloster

syn-alloster

alloster, at high orthoster concentrations it can still lift the response further with ceiling;

allo-synergy or synergy

the effect of syn-allosters, different from super-agonism

ago-syn-alloster

alloster, both activates receptors in absence of orthoster and increases activity even at high orthoster concentration. Both increases in activity have ceiling

allo-ago-synergy

the effect of ago-syn-allosters, different from super-agonism

enhancer

alloster, moves orthoster d-r curves to the left with ceiling

allo-competitor

alloster, moves orthoster d-r curves right with or without ceiling

allo-mixed-competitor

alloster, decreases activity and changes apparent affinity constants for orthosters. Orthoster d-r curves with allo-mixed-competitor are right-shifted but may have increased affinity

enhancer-inhibitor

alloster that both increases apparent affinity constants and decreases activity for orthosters. With enhancer-inhibitor, orthoster d-r curves move left with ceiling

ago-inverse-alloster

alloster, stimulates activity from an allosteric site in its own right, but with an activity which is reduced with increasing orthoster concentrations

ortho-alloster or bitopic ligand

compound with moieties for simultaneous binding and activation at both orthosteric and allosteric receptor binding sites

synagics

the study of equilibrium and steady-state concentration-responses of ligand interactions with receptive units such as protein macromolecules

positive and negative allosteric modulators

(PAMs* and NAMs**) - ligands that increase or decrease receptor activity directly or indirectly from an allosteric binding site.