Neurophysiology of dexmedetomidine (dex). (A) Dexmedetomidine acts presynaptically to block the release of norepinephrine (NE) from neurons projecting from the locus coeruleus (LC) to the basal forebrain (BF), the preoptic area (POA) of the hypothalamus, and the intralaminar nucleus (ILN) of the thalamus and the cortex. Blocking the release of NE in the POA leads to activation of its inhibitory γ-aminobutyric acid (GABA)ergic and galanergic (Gal) projections to dorsal raphe (DR) that releases serotonin (5HT), the tuberomammillary nucleus (TMN) that releases histamine (His), the LC, the ventral periaqueductal gray (PAG) that releases dopamine, the lateral dorsal tegmental (LDT) nucleus, and the pedunculopontine tegmental (PPT) nucleus that release acetylcholine (ACh). These actions lead to decreased arousal by inhibition of the arousal centers. (B) Ten-second electroencephalogram segment showing spindles, intermittent 9 to 15 Hz oscillations (underlined in red), characteristic of dexmedetomidine sedation. (C) The spindles are most likely produced by intermittent oscillations between the cortex (orange region) and thalamus (light green region). DRG = dorsal root ganglia; PAF = peripheral afferent; PN = projection neuron. A is adapted, with permission, from Brown, Purdon, and Van Dort: General anesthesia and altered states of arousal: A systems neuroscience analysis. Annu Rev Neurosci 2011; 34:601–28. Adaptations are themselves works protected by copyright. In order to publish this adaptation, authorization has been obtained both from the owner of the copyright of the original work and from the owner of copyright of the translation or adaptation. DRG = dorsal root ganglia; PAF = peripheral afferent; PN = projection neuron.