Inverse agonist

[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.

Both endogenous and exogenous inverse agonists have been identified, as have drugs at ligand gated ion channels and at G protein-coupled receptors.

6α-naltrexo, 6β-naltrexol, 6β-naloxol, and 6β-naltrexamine acted neutral antagonists regardless of opioid binding and caused significantly reduced withdrawal jumping when compared to naloxone and naltrexone.

[11] To illustrate, mechanistic models have been made for how inverse agonists induce their responses on G protein-coupled receptors (GPCRs).

[12] Under this model, current thinking is that the GPCRs can exist in a continuum of active and inactive states when no ligand is present.

Dose response curves of a full agonist, partial agonist, neutral antagonist, and inverse agonist
Figure 2: Example of changes in Intrinsic activity based on mutations and the presence of inverse agonists. (assuming the inverse agonist has the same binding affinity for both the normal and mutated receptor)