agonismantagonism

Agonismantagonism is a pharmacological concept describing situations in which a single ligand or signaling agent can produce both activating (agonist) and inhibiting (antagonist) effects depending on receptor subtype, tissue context, or the presence of endogenous ligands. The term is sometimes used to describe mixed agonist–antagonist drugs, partial agonists, or ligands that interact with multiple receptor types.

Mechanisms underlying agonismantagonism include (1) multi-receptor activity, where a molecule acts as an agonist at one receptor and as an antagonist at another, thereby producing opposing effects in different signaling pathways; (2) partial agonism, in which a compound produces submaximal receptor activation and can block the actions of a full agonist by occupying receptor sites; and (3) context-dependent effects, such as tissue-specific receptor distribution or differing downstream signaling environments that change the net outcome of receptor engagement.

Examples often cited in pharmacology involve opioid receptor ligands and other mixed-action agents. Buprenorphine is commonly described as a mu receptor partial agonist with antagonistic or low-activity effects at other opioid receptors, contributing to analgesia with a ceiling effect on respiratory depression. Nalbuphine and pentazocine are cited as drugs with kappa agonist activity and mu antagonist activity, producing analgesia via one pathway while dampening mu-mediated effects via another. Such agents are used clinically for pain management and to modulate risk profiles associated with pure agonists, though their mixed actions can complicate withdrawal risk and dosing strategies in certain patients.

See also: partial agonism, antagonist, inverse agonism, mixed agonist–antagonist drugs, receptor pharmacology.