Comment on "Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition"

Science. 2012 Aug 10;337(6095):646; author reply 646. doi: 10.1126/science.1221810.


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.

Publication types

  • Comment

MeSH terms

  • Animals
  • Body Temperature Regulation*
  • Chemoreceptor Cells / physiology*
  • Clozapine / analogs & derivatives*
  • Neural Inhibition*
  • Neurons / physiology*
  • Respiration*
  • Serotonin / physiology*


  • Serotonin
  • Clozapine