Vmn1r90 Inhibitors

Chemical inhibitors of vomeronasal 1 receptor 90 (V1R90) employ various mechanisms to disrupt its function. Capsaicin, for example, binds directly to TRPV1 receptors, which have a complex interplay with V1R90. Through this binding, capsaicin alters the conformation of these TRPV1 receptors, which in turn hinders the functional capability of V1R90 by preventing its typical ligand binding and activation. Similarly, chloroquine impacts V1R90 indirectly by accumulating in acidic vesicles and increasing their pH, which can impede the trafficking of the receptor to the membrane, a process essential for its activation. Ruthenium Red and verapamil both act on calcium channels, with the former blocking them and the latter inhibiting calcium influx. Given the calcium-dependency of V1R90 signaling, these actions result in the inhibition of the receptor's signaling cascade.

Further disrupting V1R90 signaling, suramin inhibits purinergic receptors, which can lower calcium levels and thus impede V1R90 function. BAPTA, by sequestering intracellular calcium, and thapsigargin, by depleting calcium stores via SERCA inhibition, also lead to a reduction in the calcium-dependent signaling pathways upon which V1R90 relies. Genistein's approach involves the inhibition of tyrosine kinases, which are vital for the phosphorylation processes that V1R90 needs for signal transduction. ML-7 and Y-27632 disrupt the cytoskeletal dynamics by inhibiting myosin light chain kinase and ROCK, respectively, which are necessary for the proper signaling and expression of V1R90. Finally, U73122 and NF449 specifically target elements of the G-protein signaling pathway; U73122 inhibits phospholipase C, while NF449 is selective for the Gs-alpha subunit, both leading to a downregulation of the receptor's activity by hampering necessary signaling events.