Receptor activated solely by a synthetic ligand

[5] Another inhibitory Gi-DREADD is the kappa-opioid-receptor (KOR) DREADD (KORD) which is selectively activated by salvinorin B (SalB).

[9] Recent findings suggest that systemically administered CNO does not readily cross the blood-brain-barrier in vivo and converts to clozapine which itself activates DREADDs.

It has been reported that Compound 21 has excellent bioavailability, pharmacokinetic properties and brain penetrability and does not undergo reverse metabolism to clozapine.

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.

[2] Viral expression of DREADD proteins, both in-vivo enhancers and inhibitors of neuronal function, have been used to bidirectionally control behaviors in mice (e.g odor discrimination).

[21] Conklin and colleagues designed the first GPCR which could be activated only by a synthetic compound[22] and has gradually been gaining momentum.