Inverse agonist

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Dose-response curve of an inverse agonist compared to a full agonist.

In pharmacology, substances that bind to a spontaneously active receptor and reduce its activity are called inverse agonists . In contrast to an agonist , an inverse agonist thus leads to a negative effect.

Occasionally the inverse agonists are counted among the antagonists . Just as imprecisely, negative allosteric modulators are sometimes called inverse agonists.

Theoretically, an inverse agonism can be observed at all receptors that show spontaneous activity (constitutive activity). For example, antihistamines inhibit the spontaneously active histamine receptors H 1 , H 2 and H 3 and are therefore u. a. used as antiallergic drugs . Other target molecules for the development of inverse agonists are, for example, the beta-adrenoceptors , the dopamine receptors D 2 and D 3 , the serotonin receptors 5-HT 1A , 5-HT 1B , 5-HT 2C and 5-HT 7 , the formyl peptide receptor, the VIP Receptor and the viral chemokine receptor US28, which also have spontaneous activity under physiological conditions or show as a result of pathological changes (e.g. mutation or overexpression ).

literature

  • Kenakin, T. (2004): Efficacy as a vector: the relative prevalence and paucity of inverse agonism. In: Mol. Pharmacol. Vol. 65, pp. 2-11. PMID 14722230
  • de Ligt, RA et al. (2000): Inverse agonism at G protein-coupled receptors: (patho) physiological relevance and implications for drug discovery. In: Br. J. Pharmacol. Vol. 130, pp. 1-12. PMID 10780991