General terms used to describe drug action

Term Suggested Usage Notes
Agonist A ligand that binds to a receptor and alters the receptor state resulting in a biological response. Conventional agonists increase receptor activity, whereas inverse agonists (see Table 6) reduce it. “Receptor activity” may be determined by: the proportion of receptor in an active conformation (e.g., R* vs. R), post-translational modifications (e.g., phosphorylation), or some other mechanism such as subcellular targeting.
Agonists may act by combining either with the same site(s) as the endogenous agonist (primary or orthosteric site) or, less commonly, with a different region of the receptor macromolecule (allosteric or allotopic site). Agonists in the second category are sometimes referred to as allosteric (allotopic) activators or allosteric (allotopic) agonists.
Some agonists (e.g., glutamate) may only be effective in the presence of another ligand (e.g., glycine in the case of glutamate) that binds to a different site on the receptor macromolecule. Under these circumstances, glutamate is referred to as the primary agonist and glycine as a co-agonist.
Antagonist A drug that reduces the action of another drug, generally an agonist. Many antagonists act at the same receptor macromolecule as the agonist. (see Table 7 for more details). Functional antagonism may include mechanisms such as: indirect antagonism, which is competition by the inhibitor for the binding site of an intermediate macromolecule that links the binding of the administered agonist to the effect observed (e.g., adrenoceptor antagonist blockade of the actions of tyramine or protein kinase A inhibitors blocking β adrenoceptor agonist effects) or physiological antagonism in which the action of one agonist exerts an opposite effect to that of the original agonist—usually through a different receptor (e.g., muscarinic agonist inhibition of β adrenoceptor-stimulated adenylyl cyclase activity in the heart).
Antagonism may also result from combination with the substance being antagonized (chemical antagonism). Functional antagonism occurs at cellular sites distinct from the receptor mediating the agonist response.
Allosteric (allotopic) modulator A ligand that increases or decreases the action of an (primary or orthosteric) agonist or antagonist by combining with a distinct (allosteric or allotopic) site on the receptor macromolecule. Allosteric (allotopic) enhancers are modulators that enhance orthosteric ligand affinity and/or agonist efficacy while having no effect on their own. Allosteric (allotopic) antagonists are modulators that reduce orthosteric ligand affinity and/or agonist efficacy. Allosteric (allotopic) agonists or activators are ligands that are able to mediate receptor activation in their own right by binding to a recognition domain on the receptor macromolecule that is distinct from the primary (orthosteric) site. Neutral allosteric (allotopic) ligands bind to an allosteric site without affecting the binding or function of orthosteric ligands but can still block the action of other allosteric modulators that act via the same allosteric site.
Syntopic interaction An interaction between ligands that bind to the same recognition site, or to recognition sites that overlap, on the receptor macromolecule. This term is most commonly associated with the description of competitive interactions between ligands that bind to the primary (orthosteric) site on a receptor, but need not be restricted to this specific situation. A syntopic interaction can also occur between different ligands that share a similar recognition domain (e.g., a common allosteric site) anywhere on the receptor macromolecule.
Allosteric (allotopic) interaction An interaction between ligands that bind to distinct, non-overlapping, recognition sites on the receptor macromolecule. The terms syntopic and allotopic are recommended to distinguish between interactions that occur at a common (same) site versus interactions that occur between different sites, respectively. Accordingly, the term allotopic can be used interchangeably with the term allosteric when describing cross-interactions between different sites on a receptor macromolecule. The term syntopic should be confined to defining interactions at a common site and should not be used interchangeably with the term orthosteric; the latter term specifically refers to the primary (endogenous agonist-binding) recognition site on the receptor.
Allosteric transition The isomerization of a receptor macromolecule between multiple conformational states. Different authors have used the term, allosteric, in different ways (see Colquhoun, 1998; Christopoulos and Kenakin, 2002). One common use of the term is to describe any mechanism that involves the isomerization of a receptor between two or more conformational states that can each display a different affinity for a given ligand. A second common use of the term is to explicitly describe an interaction between two topographically distinct recognition sites on a receptor macromolecule in a given conformational state. In order to accommodate both uses, it is recommended that the term allosteric transition be used when describing receptor isomerization mechanisms, and the term allosteric (or allotopic) interaction, be used when explicitly describing a cross-interaction between multiple ligands concomitantly bound to a receptor macromolecule.