Pharmacodynamics

Inverse Agonist

TRTers Agonist
Also known as:Negative agonist

A ligand that binds to a receptor with constitutive (ligand-independent) activity and reduces that basal activity, producing an effect opposite in direction to that of an agonist.

In depth

Receptors are thought to exist in equilibrium between inactive (R) and active (R*) conformations even without ligand (two-state model). Agonists preferentially stabilise R*, inverse agonists preferentially stabilise R, and neutral antagonists bind both states equally, blocking agonists and inverse agonists alike without changing basal activity.

Inverse agonism can be observed only where receptors show constitutive activity, as with several GPCRs (e.g. histamine H1 and H2 receptors, β-adrenoceptors) and constitutively active mutant receptors. Many drugs classified clinically as antagonists, including most H1 antihistamines, behave as inverse agonists in experimental systems; at the benzodiazepine site, β-carbolines are classic experimental inverse agonists with anxiogenic and proconvulsant effects.

Example drugs

Pimavanserin Cetirizine Loratadine
TRIn Turkish

Ters Agonist

Konstitütif (liganddan bağımsız) aktiviteye sahip bir reseptöre bağlanarak bu bazal aktiviteyi azaltan ve agoniste zıt yönde etki oluşturan liganddır.

Reseptörlerin ligand yokluğunda bile inaktif (R) ve aktif (R*) konformasyonlar arasında dengede bulunduğu kabul edilir (iki durum modeli). Agonistler R* durumunu, ters agonistler R durumunu tercihli olarak stabilize eder; nötr antagonistler ise her iki duruma eşit afiniteyle bağlanarak bazal aktiviteyi değiştirmeden hem agonistlerin hem de ters agonistlerin etkisini engeller.

Ters agonizma yalnızca konstitütif aktivite gösteren reseptörlerde gözlenebilir; bazı GPCR'ler (örneğin histamin H1 ve H2 reseptörleri, β-adrenerjik reseptörler) ve konstitütif olarak aktif mutant reseptörler buna örnektir. Klinikte antagonist olarak sınıflandırılan birçok ilaç, örneğin H1 antihistaminiklerin çoğu, deneysel sistemlerde ters agonist gibi davranır; benzodiazepin bağlanma bölgesinde β-karbolinler anksiyojenik ve prokonvülsan etkili klasik deneysel ters agonistlerdir.

Diğer adları:Negatif agonist
Updated 24.09.2026 1 views Educational reference — verify against current sources before clinical use.

Read next

AgonistAgonist

A drug or endogenous substance that binds to a receptor and activates it, producing a biological response; it possesses both affinity and efficacy (intrinsic activity).

 AntagonistAntagonist

A drug that binds to a receptor or other target without activating it (affinity but no efficacy) and thereby prevents or reduces the response to an agonist.

 Intrinsic Activityİntrinsik Aktivite

The ability of a drug, once bound, to activate its receptor and produce a response, expressed relative to a full agonist on a scale from 0 (antagonist) to 1 (full agonist); inverse agonists have negative values.

 ReceptorReseptör

A macromolecule, usually a protein, to which a drug or endogenous ligand binds specifically and thereby initiates a change in cell function that produces a biological response.

 G Protein-Coupled ReceptorG Proteinine Kenetli Reseptör

A member of the largest family of cell-surface receptors, a single polypeptide with seven transmembrane α-helices that transduces ligand binding into intracellular signals by activating heterotrimeric G proteins.

 Partial AgonistKısmi Agonist

An agonist that, even when occupying all available receptors, produces a maximal response smaller than that of a full agonist; its intrinsic activity lies between 0 and 1.