RASSLs and DREADDs are families of designer G-protein-coupled receptors (GPCRs) built specifically to allow for precise spatiotemporal control of GPCR signaling in vivo. These engineered GPCRs are unresponsive to endogenous ligands but can be activated by nanomolar concentrations of pharmacologically inert, drug-like small molecules. Currently, RASSLs exist for the interrogation of several GPCR signaling pathways, including those activated by Gs, Gi, Gq, Golf and β-arrestin.   A major cause for success of RASSL resources has been open exchange of DNA constructs, and RASSL related resources.
The hM4Di-DREADDs inhibitory effects are a result of the CNOs stimulation and resulting activation of the G-protein inwardly rectifying potassium (GIRK) channels. This causes hyperpolarization of the targeted neuronal cell and thus attenuates subsequent activity.