Chemogenetics revealed: DREADD occupancy and activation via converted clozapine
National Institute on Drug Abuse · Johns Hopkins University · +3 more institutions
Abstract
The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency. Upon systemic CNO injections, converted clozapine readily enters the brain and occupies central nervous system-expressed…
Citation impact
- FWCI
- 58.56
- Percentile
- 100%
- References
- 22
Authors
13- JLJuan L. GomezCorresponding
National Institute on Drug Abuse
- JBJordi BonaventuraCorresponding
National Institute on Drug Abuse
- WGWojciech G. Lesniak
Johns Hopkins University, Johns Hopkins Medicine
- WBWilliam B. Mathews
Johns Hopkins University, Johns Hopkins Medicine
- PSPolina Sysa‐Shah
Johns Hopkins University, Johns Hopkins Medicine
Topics & keywords
- Receptor
- Clozapine
- Neuroscience
- In vivo
- Pharmacology
- Chemistry
- Medicine
- Biology