DREADD Ligands

DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) are genetically modified G-protein coupled receptors (GPCRs) that are activated by physiologically inert designer synthetic ligands (designer drugs).

Products
Background
Literature

Activators

Cat No Product Name / Activity
4936 Clozapine N-oxide
Activator of muscarinic DREADDs
6329 Clozapine N-oxide dihydrochloride
Activator of muscarinic DREADDs; water soluble version of Clozapine N-oxide (Cat. No. 4936)
5548 DREADD agonist 21
Potent muscarinic DREADD agonist
6422 DREADD agonist 21 dihydrochloride
Potent muscarinic DREADD agonist; water soluble version of DREADD agonist 21 (Cat. No. 5548)
5549 Perlapine
Potent muscarinc DREADD agonist
5611 Salvinorin B
Activates the κ-opioid DREADD (KORD)

DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) are genetically modified G-protein coupled receptors (GPCRs) that are activated by physiologically inert designer synthetic ligands (designer drugs). Studies have provided evidence that DREADDs are functionally similar to their wild type receptors, therefore they are useful tools for the study of GPCR signaling.

The first DREADDs to be developed were derived from human muscarinic acetylcholine receptors (mAChRs) and termed hM1-5D. These receptors have mutations in their orthosteric binding site, abolishing their affinity for the endogenous ligand ACh, while rendering them responsive to the small molecule clozapine-N-oxide (CNO). CNO exhibits no appreciable affinity (Ki >1 μM) for any other relevant CNS target, and therefore is a selective tool for the activation of DREADDs.


DREADD Ligands Mechanism of Action

DREADD Ligands Mechanism of Action.

Figure 1: Schematic outlining the mechanism of action of DREADD ligand signaling through DREADDs. DREADD ligands that induce Gq signaling provoke neuronal firing, whereas those that induce Gi signaling cause neuronal silencing. Clozapine N-oxide is a non-selective muscarinic DREADD agonist, which activates Gq-mediated signaling on binding to M1, M3 and M5 DREADDs, and Gi-mediated signaling on binding to M2 and M4 DREADDs.


DREADDs have been shown to be effective for the modulation of neuronal activity. hM3Dq is a Gq-coupled GPCR that activates neuronal firing upon CNO stimulation, while hM4Di is a Gi-coupled GPCR that inhibits neuronal firing through activation of GIRK (Kir3) channels. These DREADDs have also been shown to have applications in vivo. Activation of hM3Dq expressing locus coeruleus neurons by CNO enhanced memory in a mouse model of Down syndrome. Furthermore injection of hM3Dq into the paraventricular hypothalamus (PVH) suppressed hyperphagia in PVH LMO4-deficient obese mice, with activation of hM4Di having the opposite effect.

A new DREADD has since been developed from the κ opioid receptor (KOR), and termed KORD. KORD is activated by the pharmacologically inert small molecule salvinorin B, and will enable the simultaneous interrogation of KOR and mAChR signaling. The development of further DREADDs and small molecule DREADD modulators is currently ongoing.

Literature for DREADD Ligands

Tocris offers the following scientific literature for DREADD Ligands to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


GPCR

GPCR Product Listing

A collection of over 450 products for G protein-coupled receptors, the listing includes research tools for the study of:

  • Rhodopsin-like Receptors
  • Secretin-like Receptors
  • Glutamate Receptors
  • Frizzled Receptors
  • GPCR Signaling
Chemogenetics

Chemogenetics Research Bulletin

Produced by Tocris, the chemogenetics research bulletin provides an introduction to chemogenetic methods to manipulate neuronal activity. It outlines the development of RASSLs, DREADDs and PSAMs, and the use of chemogenetic compounds. DREADD ligands and PSEMs available from Tocris are highlighted.