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Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens agonist-mediated responses rather than provoking a biological response itself upon binding to a receptor.〔"(Pharmacology Guide: In vitro pharmacology: concentration-response curves )." ''GlaxoWellcome.'' Retrieved on December 6, 2007.〕 They are sometimes called blockers; examples include alpha blockers, beta blockers, and calcium channel blockers. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors. Antagonists mediate their effects by binding to the active (orthosteric = right place) site or to allosteric (= other place) sites on receptors, or they may interact at unique binding sites not normally involved in the biological regulation of the receptor's activity. Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist–receptor binding. The majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites on receptors.
==Receptors==
(詳細はreceptors are large protein molecules that can be activated by the binding of a ligand (such as a hormone or drug).〔T. Kenakin (2006) A Pharmacology Primer: Theory, Applications, and Methods. 2nd Edition Elsevier ISBN 0-12-370599-1〕 Receptors can be membrane-bound, occurring on the cell membrane, or intracellular, such as on the nucleus or mitochondrion. Binding occurs as a result of noncovalent interaction between the receptor and its ligand, at locations called the binding site on the receptor. A receptor may contain one or more binding sites for different ligands. Binding to the active site on the receptor regulates receptor activation directly.〔 The activity of receptors can also be regulated by the binding of a ligand to other sites on the receptor, as in allosteric binding sites. Antagonists mediate their effects through receptor interactions by preventing agonist-induced responses. This may be accomplished by binding to the active site or the allosteric site. In addition, antagonists may interact at unique binding sites not normally involved in the biological regulation of the receptor's activity to exert their effects.〔
The term ''antagonist'' was originally coined to describe different profiles of drug effects. The biochemical definition of a receptor antagonist was introduced by Ariens and Stephenson〔 of the original article.〕 in the 1950s. The current accepted definition of receptor antagonist is based on the receptor occupancy model. It narrows the definition of antagonism to consider only those compounds with opposing activities at a single receptor. Agonists were thought to turn "on" a ''single'' cellular response by binding to the receptor, thus initiating a biochemical mechanism for change within a cell. Antagonists were thought to turn "off" that response by 'blocking' the receptor from the agonist. This definition also remains in use for physiological antagonists, substances that have opposing physiological actions, but act at different receptors. For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by alpha-adrenergic receptor activation.
Our understanding of the mechanism of drug-induced receptor activation and receptor theory and the biochemical definition of a receptor antagonist continues to evolve. The two-state model of receptor activation has given way to multistate models with intermediate conformational states. The discovery of functional selectivity and that ligand-specific receptor conformations occur and can affect interaction of receptors with different second messenger systems may mean that drugs can be designed to activate some of the downstream functions of a receptor but not others. This means efficacy may actually depend on where that receptor is expressed, altering the view that efficacy at a receptor is receptor-independent property of a drug.〔
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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