The Transition from Agonist to Antagonist Activity. Symmetry and other Considerations.

Specificity, stereoselectivity, and the factoring of ligands and drugs as agonists and antagonists with qualitative and quantitative differences in activity have long been recognized as fundamental properties of drug-receptor interactions. Increasingly, it is recognized that ligands need to be considered in terms of a continuum of agonist-partial agonist-antagonist properties and that these properties are, furthermore, not invariant but can be modified, both qualitatively and quantitatively, according to receptor density, receptor expression, and the coupling factors involved. Furthermore, certain symmetry is imposed on ligand-receptor interactions with the existence of agonists, antagonists, and neutral antagonists. It is quite clear that agonist/antagonist properties are not simple functions of the ligand alone, but are also properties of the receptor and its associated coupled effectors. The nature and stoichiometry of the receptor-effector components are critical determinants of the characteristics of the response. Additionally, constitutively active receptors initiate response in the absence of ligand, and receptors may also contain ligand functionality as an integral component of the receptor structure itself. Receptors and ligands enjoy a complementarity and symmetry of interaction that befit their mutual dependence.