气候变化领域集成服务门户(CCPortal): Chemogenetics revealed: DREADD occupancy and activation via converted clozapine

CCPortal

DOI	10.1126/science.aan2475
	Chemogenetics revealed: DREADD occupancy and activation via converted clozapine
	Gomez J.L.; Bonaventura J.; Lesniak W.; Mathews W.B.; Sysa-Shah P.; Rodriguez L.A.; Ellis R.J.; Richie C.T.; Harvey B.K.; Dannals R.F.; Pomper M.G.; Bonci A.; Michaelides M.
发表日期	2017
ISSN	0036-8075
起始页码	503
结束页码	507
卷号	357 期号:6350
英文摘要	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 DREADDs, whereas systemic subthreshold clozapine injections induce preferential DREADD-mediated behaviors. © 2017, American Association for the Advancement of Science. All rights reserved.
英文关键词	carbon 11; clozapine n oxide; designer drug; designer receptors exclusively activated by designer drug; muscarinic receptor; unclassified drug; clozapine; clozapine N-oxide; designer drug; muscarinic M3 receptor; muscarinic M4 receptor; brain; cells and cell components; chemical analysis; drug; gene expression; technological change; animal experiment; animal tissue; Article; blood brain barrier; brain tissue; chemogenetics; competitive binding assay; controlled study; genetics; human; mouse; nonhuman; positron emission tomography; priority journal; rat; analogs and derivatives; animal; binding competition; brain; drug effects; genetic procedures; HEK293 cell line; metabolism; nerve cell; transgenic mouse; Animalia; Animals; Binding, Competitive; Brain; Clozapine; Designer Drugs; Genetic Techniques; HEK293 Cells; Humans; Mice; Mice, Transgenic; Neurons; Receptor, Muscarinic M3; Receptor, Muscarinic M4
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/243833
作者单位	Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse (NIDA) Intramural Research Program, Baltimore, MD 21224, United States; Department of Radiology, Johns Hopkins School of Medicine, Baltimore, MD 21205, United States; Optogenetics and Transgenic Technology Core, NIDA Intramural Research Program, Baltimore, MD 21224, United States; Synaptic Plasticity Section, NIDA Intramural Research Program, Baltimore, MD 21224, United States; Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD 21205, United States
推荐引用方式 GB/T 7714	Gomez J.L.,Bonaventura J.,Lesniak W.,et al. Chemogenetics revealed: DREADD occupancy and activation via converted clozapine[J],2017,357(6350).
APA	Gomez J.L..,Bonaventura J..,Lesniak W..,Mathews W.B..,Sysa-Shah P..,...&Michaelides M..(2017).Chemogenetics revealed: DREADD occupancy and activation via converted clozapine.Science,357(6350).
MLA	Gomez J.L.,et al."Chemogenetics revealed: DREADD occupancy and activation via converted clozapine".Science 357.6350(2017).