Technical Comments

Comment on “Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition”

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Science  10 Aug 2012:
Vol. 337, Issue 6095, pp. 646
DOI: 10.1126/science.1221810

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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.

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