Inverse agonist

Not to be confused with Antagonist or Protagonist.
Dose response curves of a full agonist, partial agonist, neutral antagonist, and inverse agonist

In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist.

A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either;[1] they are in fact sometimes called blockers (examples include alpha blockers, beta blockers, and calcium channel blockers). Inverse agonists have opposite actions to those of agonists but the effects of both of these can be blocked by antagonists.[2]

A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level of activity in the absence of any ligand.[3] An agonist increases the activity of a receptor above its basal level, whereas an inverse agonist decreases the activity below the basal level.

The efficacy of a full agonist is by definition 100%, a neutral antagonist has 0% efficacy, and an inverse agonist has < 0% (i.e., negative) efficacy.

  1. ^ Kenakin T (April 2004). "Principles: receptor theory in pharmacology". Trends in Pharmacological Sciences. 25 (4): 186–92. doi:10.1016/j.tips.2004.02.012. PMID 15063082.
  2. ^ Nutt D, Stahl S, Blier P, Drago F, Zohar J, Wilson S (January 2017). "Inverse agonists - What do they mean for psychiatry?". European Neuropsychopharmacology. 27 (1): 87–90. doi:10.1016/j.euroneuro.2016.11.013. hdl:10044/1/43624. PMID 27955830. S2CID 25113284.
  3. ^ Berg, Kelly A; Clarke, William P (2018-08-06). "Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity". International Journal of Neuropsychopharmacology. 21 (10): 962–977. doi:10.1093/ijnp/pyy071. ISSN 1461-1457. PMC 6165953. PMID 30085126.