Orthosterische

Orthosterische is an adjective used in pharmacology and biochemistry to describe the primary ligand-binding site of a receptor, or ligands that bind to that same site. The term derives from Greek roots meaning the correct or primary place of binding. In this sense, orthosteric sites are the binding pockets for the endogenous signaling molecules that naturally regulate receptor activity.

Orthosteric ligands include agonists, antagonists, and inverse agonists. Agonists activate the receptor, antagonists block activation, and inverse agonists reduce any constitutive (basal) receptor activity. Because orthosteric ligands compete with the endogenous ligand for the same site, their effects are influenced by endogenous ligand levels, receptor density, and affinity. Receptors such as acetylcholine receptors and adrenergic receptors illustrate orthosteric interactions, where acetylcholine or norepinephrine binds at the orthosteric site.

A major conceptual distinction is between orthosteric and allosteric ligands. Allosteric ligands bind to separate allosteric sites and modulate receptor function by changing affinity or efficacy for the orthosteric ligand, without directly occupying the primary site. This separation can offer advantages in selectivity and safety, and allosteric modulators are a focus in drug development for many receptor families, including GPCRs and ion channels.

In practice, the orthosteric concept is central to understanding receptor pharmacodynamics, guiding drug design, and interpreting how endogenous signaling and therapeutic agents interact at the primary binding site.