FIGURE 7.
Pharmacological mechanisms for the modulation of GPR55. LPI is suggested to primarily bind the GPR55 orthosteric binding site. GPR55 may also contain an allosteric binding site. These observations raise at least two possibilities as follows. Left, one possibility is that certain arylpyrazole ligands actually represent bitopic ligands of GPR55. These ligands may have the capacity to modulate both the orthosteric (agonists) and the allosteric site through different pharmacophores. The second possibility is that AM251 and certain arylpyrazole analogues are only allosteric ligands that are ago-allosteric alone. Right, in the presence of LPI, arylpyrazoles can also behave as allosteric inhibitors and GW405833 as an allosteric enhancer. In addition, a number of Cannabis sativa constituents appear to inhibit ERK1/2 phosphorylation in an allosteric manner.