title: Comment on "Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition".
abstract: Ray et al. (Reports, 29 July 2011, p. 637) assume that clozapine-N4-oxide (CNO) represents a "biologically inert synthetic ligand" that selectively activates the M4 muscarinic receptor-based DREADD (designer receptor exclusively activated by a designer drug). In contrast, due to the redox cycling of CNO with clozapine and to their cell membrane permeability, CNO is biologically active and its conversion products are capable of undermining DREADD effects.
authors.affiliation: Department of Psychiatry and Psychotherapy, Clinic Offenbach, Teaching Hospital of Goethe University, D-63069 Offenbach, Germany. stefloeffler@t-online.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Löffler
authors.forename: Jochen
authors.initials: J
authors.lastname: Körber
authors.forename: Udo
authors.initials: U
authors.lastname: Nubbemeyer
authors.forename: Karin
authors.initials: K
authors.lastname: Fehsel
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation; D002628:Chemoreceptor Cells / Q000502:physiology*; D003024:Clozapine / Q000031:analogs & derivatives*; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology*; D012119:Respiration; D012701:Serotonin / Q000502:physiology*
chemical_list: D012701:Serotonin; D003024:Clozapine